Example 1
The 7-aza-thienylpyridine compounds in Table 1 can be synthesized using methods described in Example 1. For some compounds, some of the reactions described in Example 2 and/or Example 3, below, can be used to prepare the compounds.
[Figure (not displayed)]
To dry N-isopropylpropan-2-amine (1.2 equiv.) in THE (0.3 M) at 0° C. is added n-butyllithium (2.5 M in hexane) (1.2 equiv.) slowly and the mixture is stirred for 10 min. The LDA solution in THE is used directly. To a solution of 3-bromo-2-chloro-5-fluoro-pyridine (A, 1 equiv.) in THE (0.3 M) at −78° C. is added the LDA solution and the resulting dark mixture is stirred for 45 min. Chloro(trimethyl)silane (1.7 equiv.) is added and the mixture is allowed to warm to rt within ca. 15 h. The reaction mixture is quenched with water, the layers separated, and the aqueous layer extracted with ethylacetate. The organic layers are combined, evaporated with silica gel and the free-flowing silica gel is loaded on a column and (3-bromo-2-chloro-5-fluoro-6-methyl-4-pyridyl)-trimethyl-silane (B) is purified by silica gel chromatography.
To a solution of (3-bromo-2-chloro-5-fluoro-4-pyridyl)-trimethyl-silane (B, 1 equiv.) in THE (0.25 M) at −78° C. is added LDA solution (1.2 equiv.) prepared as above and the resulting dark mixture is stirred for 45 min. Iodomethane (10 equiv.) is added and the mixture is allowed to warm to rt within ca. 15 h. The reaction mixture is quenched with water, the layers separated, and the aqueous layer further extracted with ethylacetate. The organic layers are combined, evaporated with silica gel and the free-flowing silica gel loaded on a column and (3-bromo-2-chloro-5-fluoro-6-methyl-4-pyridyl)-trimethyl-silane (C) is purified via silica gel chromatography.
(3-bromo-2-chloro-5-fluoro-6-methyl-4-pyridyl)-trimethyl-silane (C, 1 equiv.) is dissolved in THE (0.67 M), cooled to 0° C., and tetrabutylammonium fluoride (in THF) (1.2 equiv.) is added and the mixture stirred at 0° C. After 10 min the reaction is quenched with NH4Cl(aq) and diluted with EtOAc. The organic phase is washed with water twice, dried, filtered, concentrated, and loaded on a column and 3-bromo-2-chloro-5-fluoro-6-methylpyridine (D) is purified via silica gel chromatography.
[Figure (not displayed)]
To a solution of 3-bromo-2-chloro-5-fluoro-6-methylpyridine (A, 1 equiv.) in tetrahydrofuran (0.40 M) at −96° C. (internal temperature), lithium diisopropylamide solution (1.2 equiv.; 2 M in tetrahydrofuran) is added over a period of 60 min, maintaining internal temperature between −96 to −84° C. and the reaction mixture is maintained at −96 to −90° C. for 2 h. Carbon dioxide gas is purged into the reaction mixture for 35 minutes, maintaining internal temperature at −95 to −78° C. Progress of the reaction is monitored by TLC and the reaction mixture is warmed to −50 to −45° C., quenched with saturated aqueous ammonium chloride solution, and stirred for 10 min. The solution is acidified to pH 2.0-1.5 with 6 N hydrochloric acid, diluted with ethyl acetate and the organic layer washed with water. The aqueous layer is extracted with ethyl acetate and the combined organic layers are concentrated under reduced pressure, stirred in dichloromethane and the solid precipitated is filtered, washed with dichloromethane, and dried under vacuum to afford 3-bromo-2-chloro-5-fluoro-6-methylisonicotinic acid (B).
To a solution of 3-bromo-2-chloro-5-fluoro-6-methylisonicotinic acid (B, 1 equiv.) in N,N-dimethylformamide (0.32 M), acetamidine hydrochloride (C, 1.4 equiv.) is added and reaction mixture is cooled at 0° C. N,N-di-isopropylethylamine (5 equiv.) and HATU (1.1 equiv.) are added and reaction mixture is stirred at room temperature for 1 h. The reaction mixture is diluted with water, extracted with ethyl acetate and the combined organic layers are dried over anhydrous sodium sulphate, filtered and concentrated to afford 3-bromo-2-chloro-5-fluoro-N-(1-iminoethyl)-6-methylisonicotinamide (D).
To a stirred solution of 3-bromo-2-chloro-5-fluoro-N-(1-iminoethyl)-6-methylisonicotinamide (D, 1 equiv.) in tetrahydrofuran (2 M), sodium hydride (60%) (1 equiv.) is added at 0° C. and stirred for 1 h at 0° C. The reaction mass is slowly warmed to room temperature and stirred for 16 h. The reaction mass is cooled to 0° C., acidified with 2 N hydrochloric acid (pH˜2), and the resulting solid filtered, washed with 10% methanol in diethyl ether and dried to afford 5-bromo-6-chloro-2,8-dimethylpyrido[3,4-d]pyrimidin-4(3H)-one (E).
To a stirred solution of 5-bromo-6-chloro-2,8-dimethylpyrido[3,4-d]pyrimidin-4(3H)-one (E, 1 equiv.) in N,N-dimethylformamide (0.056 M), copper(I) cyanide (1.2 equiv.) is added at room temperature. The reaction is heated to 100° C. and stirred for 16 h. The reaction is quenched with 1 N hydrochloric acid, and the solid is filtered, washed with diethyl ether, and purified by via chromatography to afford 6-chloro-2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (F).
5-bromo-6-chloro-2,8-dimethylpyrido[3,4-d]pyrimidin-4(3H)-one (E, 1 equiv.), copper(I) cyanide (1.2 equiv.), and NMP (0.072 M) are combined in a sealable vessel with a stir bar. The resulting mixture is sealed, stirred, and heated at 90° C. for 20 h. Upon cooling to room temperature, the reaction mixture is diluted with 1% TFA in acetonitrile, filtered, and purified via chromatography to afford 6-chloro-2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (F).
To a solution of 5-bromo-6-chloro-2,8-dimethylpyrido[3,4-d]pyrimidin-4(3H)-one (E, 1 equiv.) in N,N-dimethylacetoamide (0.07 M) is added dicyanozinc (1.4 equiv.) and tetrakis(triphenylphosphine)palladium (2.0 equiv.) at room temperature. The mixture is degassed with argon for 5 min, and stirred for 5 h at 130° C. Upon cooling to room temperature, the mixture is diluted with dimethyl sulfoxide and acetonitrile and purified by chromatography to afford 6-chloro-2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (F).
[Figure (not displayed)]
A solution of 6-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (A, 1 equiv.) in dimethyl sulfoxide (0.23 M) is purged with argon gas for 10 minutes. 18-Crown-6 ether (1.5 equiv.) and potassium fluoride (5 equiv.) are added to the reaction mixture and purging is continued for 5 minutes and stirred in a preheated oil bath at 160° C. for 2 h. The reaction mixture is cooled, poured on to ice cold water, extracted with ethyl acetate, and the ethyl acetate layer washed with brine solution, dried over anhydrous sodium sulphate, concentrated, and triturated with diethyl ether to get 6-fluoro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (B).
[Figure (not displayed)]
To a solution of tert-butyl methyl(piperidin-4-yl)carbamate (A, 1 equiv.) and N,N-diisopropylethylamine (10 equiv.) in acetonitrile (0.35 M), 2,2,2-trifluoroethyl trifluoromethanesulfonate (2, 1.25 equiv.) is added dropwise and the mixture stirred at room temperature for 16 h. The reaction mixture is diluted with water, extracted with dichloromethane, and the organic layer dried over anhydrous sodium sulphate, filtered, concentrated, and purified by flash column chromatography to afford tert-butyl methyl(1-(2,2,2-trifluoroethyl)piperidin-4-yl)carbamate (C).
A solution of tert-butyl methyl(1-(2,2,2-trifluoroethyl)piperidin-4-yl)carbamate (C, 1 equiv.) in hydrochloride (4 M solution in 1,4-dioxane, 0.34 M) is stirred at room temperature for 4 h. The reaction mixture is concentrated to afford N-methyl-1-(2,2,2-trifluoroethyl)piperidin-4-amine hydrochloride (D).
A solution of 6-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (E, 1 equiv.) and N-methyl-1-(2,2,2-trifluoroethyl)piperidin-4-amine hydrochloride (D, 3 equiv.) in N,N-dimethylacetamide (0.24 M), potassium fluoride (8 equiv.) and 18-crown-6 (1 equiv.) are added and the reaction mixture heated at 130° C. for 16 h. The reaction mixture is cooled, diluted with water, extracted with ethyl acetate, and the organic layer washed with water, dried over anhydrous sodium sulphate, filtered, concentrated, and purified by flash column chromatography to afford 2-methyl-6-(methyl(1-(2,2,2-trifluoroethyl)piperidin-4-yl)amino)-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (F).
[Figure (not displayed)]
1,4-Dioxane (24 mL) and water (8 mL) is added to a mixture of 2,3-dibromo-5-fluoropyridine (A, 3000 mg, 11.8 mmol), cyclopropylboronic acid (1112 mg, 12.9 mmol), and cesium carbonate (8436 mg, 25.9 mmol). The mixture is bobbled with argon bubbling for 5 min. Tetrakis(triphenylphosphine)palladium (680 mg, 0.590 mmol) is added to the mixture, and the mixture is vacuumed and backfilled with argon three times. The resulting clear yellow reaction mixture is stirred for 72 h at 110° C. The mixture is diluted with ethyl acetate, and washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration. Purification by silica gel column chromatography (0 to 5% ethyl acetate in hexane) gave 3-bromo-2-cyclopropyl-5-fluoropyridine (B).
n-Butyllithium (2.5 M in hexane, 2.1 mL, 5.30 mmol) is added to a stirred solution of diisopropylamine (0.81 mL, 5.80 mmol) in THE (5 mL) at 0° C. under argon. The resulting light yellow solution is stirred for 10 min at 0° C. and then added slowly to a stirred solution of 3-bromo-2-cyclopropyl-5-fluoropyridine (B, 1000 mg, 4.60 mmol) in tetrahydrofuran (20 mL) at −78° C. under argon. The resulting yellow reaction mixture is stirred at −78° C. under argon for 30 min and then carbon dioxide gas is bubbled in for 2 min. The mixture is stirred at −78° C. for 10 min and then warmed to room temperature over 5 min. The reaction is diluted with 0.1 N sodium hydroxide, and extracted with diethyl ether. Water layer is acidified by 3 M hydrogen chloride, and extracted with ethyl acetate twice, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration to afford 3-bromo-2-cyclopropyl-5-fluoroisonicotinic acid (C).
To a N,N-dimethylformamide (14 mL) solution of 3-bromo-2-cyclopropyl-5-fluoroisonicotinic acid (C, 730. mg, 2.81 mmol) is added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (1387 mg, 3.60 mmol) and N,N-diisopropylethylamine (2.0 mL, 11.2 mmol) at 0° C. The mixture is stirred for 5 min at room temperature, and acetamidine hydrochloride (D, 345 mg, 3.60 mmol) is added to the mixture. After stirring the mixture for 17 h at room temperature, ice-cold water is added to the mixture, and extracted with ethyl acetate twice. The combined extracts are washed with aqueous solution of ammonium chloride, aqueous solution of sodium bicarbonate, and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration. The residue is dissolved tetrahydrofuran (18 mL), and sodium hydride (60% in mineral oil, 225 mg, 5.60 mmol) is added to the mixture at 0° C. After stirring the mixture for 18 h, ice-cold water is added to the mixture, and extracted with ethyl acetate three times, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration. The residue is triturated with dichloromethane, and filtered to afford 5-bromo-6-cyclopropyl-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (E).
[Figure (not displayed)]
To a solution of ethyl 3-amino-6-chloro-5-cyano-2-methylisonicotinate (A, 0.90 g, 3.75 mmol) in 1,4-dioxane and water (4:1, 10.0 mL), phenylboronic acid (B, 0.68 g, 5.62 mmol) and potassium carbonate (1.53 g 11.25 mmol) are added. The reaction mixture is purged with argon for 5 min. Then, [1,1-bis(diphenylphospino)ferrocene] dichloropaladium(II) (complex with dichloromethane, 0.031 g, 0.037 mmol) is added and the reaction mixture is heated at 90° C. for 5 h. After this time, the reaction mixture is cooled, diluted with water, and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. This is purified by silica gel (100-200 mesh) column chromatography using 30-40% ethyl acetate in hexane to afford ethyl 3-amino-5-cyano-2-methyl-6-phenylisonicotinate (C).
To a solution of ethyl 3-amino-5-cyano-2-methyl-6-phenylisonicotinate (C, 0.6 g, 2.13 mmol) in tetrahydrofuran and water (4:1, 6 mL) at room temperature, lithium hydroxide (0.44 g, 10.67 mmol) is added. This reaction mixture is stirred at room temperature for 2 h. After this time, the reaction mixture is diluted with water, acidified with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. This is washed with diethyl ether to afford 3-amino-5-cyano-2-methyl-6-phenylisonicotinic acid (D).
To a solution of 3-amino-5-cyano-2-methyl-6-phenylisonicotinic acid (D, 0.5 g, 1.97 mmol) in N,N-dimethylformamide (5.0 mL), ammonium chloride (0.31 g, 5.92 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (0.840 g, 2.21 mmol) are added. This reaction mixture is cooled to 0° C., N,N-di-isopropylethylamine (2.7 mL, 14.70 mmol) is added, and the reaction mixture is stirred at 0° C. for 10 min. Then, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. This is purified by silica gel (100-200 mesh) column chromatography using 30-40% ethyl acetate in hexanes to afford 3-amino-5-cyano-2-methyl-6-phenylisonicotinamide (E).
A solution of 3-amino-5-cyano-2-methyl-6-phenylisonicotinamide (E, 0.4 g, 1.19 mmol), in triethylorthoacetate and acetic acid (4:1, 4 mL) is heated at 130° C. for 2 h under microwave. After this time, the reaction mixture is cooled, diluted with hexanes, and filtered to afford 2,8-dimethyl-4-oxo-6-phenyl-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (F).
[Figure (not displayed)]
To a stirred mixture of 3-chloro-5-fluoroisonicotinic acid (A, 1 equiv.) in diethyl carbonate (0.29 M) and water (0.44 M) under argon is added sodium 4,4-difluorocyclohexane-1-sulfinate (B, 3 equiv.) and the mixture is cooled to 0° C. tert-Butyl hydroperoxide (70 wt. % in water) (10 equiv.) is added and the mixture is stirred for 5 min then heated at 90° C. under argon with an oil bath for 3 h. Volatiles are removed on a rotary evaporator. The residue is taken up in a mixture of water, acetonitrile and TFA, filtered, and purified via preparatory HPLC to afford a mixture of 3-chloro-2-(4,4-difluorocyclohexyl)-5-fluoroisonicotinic acid (C) and 5-chloro-2-(4,4-difluorocyclohexyl)-3-fluoroisonicotinic acid (D).
HATU (1.1 equiv.) is added to a stirred solution of 3-chloro-2-(4,4-difluorocyclohexyl)-5-fluoroisonicotinic acid (C) and 5-chloro-2-(4,4-difluorocyclohexyl)-3-fluoroisonicotinic acid (D 1 equiv.) in DMF (0.46 M) at room temperature under argon. After 2 min N,N-diisopropylethylamine (1.1 equiv.) is added. After stirring at room temperature for 35 min a solution of acetamidine hydrochloride (2 equiv.) and N,N-diisopropylethylamine (2.2 equiv.) in DMF (5.6 M) (this is heated with a heat gun and sonicated to get all of the acetamidine dissolved) is added. The resulting solution is stirred vigorously at room temperature under argon for 1.5 h. The reaction mixture is diluted with ethyl acetate and washed three times with brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and dried under high vacuum to afford a viscous amber oil. The oil is dissolved in THE (0.046 M) with stirring under argon. Sodium hydride (2.2 equiv.) is added and the reaction mixture is stirred vigorously at room temperature under argon for 21 h. A solution of ammonium chloride (5 equiv.) in water (0.14 M) is added with vigorous stirring. The resulting mixture is partitioned between ethyl acetate and brine. The organics are dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. The residue is taken up in NMP, acetonitrile, and TFA, filtered, and purified via preparatory HPLC to afford 5-chloro-6-(4,4-difluorocyclohexyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (E) and 5-chloro-8-(4,4-difluorocyclohexyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (F)
[Figure (not displayed)]
4-Methoxybenzyl chloride (1.27 mL, 9.38 mmol) is added to a stirred mixture of 5-bromo-6-chloro-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (A, 1.98 g, 7.21 mmol) and cesium carbonate (3.29 g, 10.1 mmol) in DMA (14 mL) at room temperature under argon. The resulting mixture is stirred vigorously and heated at 50° C. under argon for 2 h. The reaction mixture is diluted with ethyl acetate (1.5 L), washed once with water, and twice with brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator with silica gel, and purified via silica gel chromatography (0-40% ethyl acetate in dichloromethane) to afford 5-bromo-6-chloro-3-(4-methoxybenzyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (B).
5-Bromo-6-chloro-3-(4-methoxybenzyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (B, 1.24 g, 3.14 mmol) is dissolved in DMF (20 mL) with stirring at 90° C. under argon. Copper(I) cyanide (338 mg, 3.77 mmol) is added and the resulting clear red solution is stirred and heated at 90° C. under argon for 1 h 40 min. While still hot the reaction mixture is diluted with ethyl acetate and filtered through Celite into ethyl acetate (600 mL). The filter cake is washed with ethyl acetate. The filtrate is shaken with water to give an emulsion which is filtered. The filtrate is partitioned between ethyl acetate and brine. The organics are washed twice with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator with silica gel, and purified via silica gel chromatography (0-100% ethyl acetate in dichloromethane) to afford 6-chloro-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (C).
6-Chloro-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (C, 100 mg, 0.293 mmol), 1-(2-fluoroethyl)piperazine bis HCl salt (D, 120 mg, 0.587 mmol), potassium carbonate (183 mg, 1.32 mmol), and NMP (1.5 mL) are combined in a sealable vessel with a stir bar. The resulting mixture is sealed, stirred vigorously, and heated at 70° C. with an oil bath for 40 min. N,N-diisopropylethylamine (0.26 mL, 1.47 mmol) is added and the resulting mixture is sealed, stirred vigorously, and heated at 100° C. with an oil bath for 1 h. After cooling to room temperature, the reaction mixture is diluted with methanol and acetic acid (0.34 mL, 5.87 mmol). The resulting mixture is filtered and purified via preparatory HPLC (10-45% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are combined and concentrated on a rotary evaporator down to ˜20 mL and then lyophilized to dryness to afford a yellow oil. The oil is dissolved in acetonitrile and loaded onto a 2-gram Strata X-C ion exchange column from Phenomenex. The column is washed sequentially with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. Eluent containing the desired product is concentrated on a rotary evaporator and dried under high vacuum to afford 6-(4-(2-fluoroethyl)piperazin-1-yl)-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (E).
To a stirred mixture of 6-(4-(2-fluoroethyl)piperazin-1-yl)-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (E, 28.2 mg, 0.065 mmol) in diethyl carbonate (0.4 mL) and water (0.2 mL) under argon is added bis((isopropylsulfinyl)oxy)zinc (F, 54.2 mg, 0.194 mmol) followed by tert-butyl hydroperoxide (70 wt. % in water) (0.092 mL, 0.666 mmol). The mixture is stirred and heated at 90° C. under argon with an oil bath for 10 min. The reaction mixture is diluted with NMP, acetic acid, and methanol, filtered, and purified via preparatory HPLC (15-65% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are loaded onto a Strata X-C ion exchange column from Phenomenex. The column is washed sequentially with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. Eluent containing the desired product is concentrated on a rotary evaporator and dried under high vacuum to afford 6-(4-(2-fluoroethyl)piperazin-1-yl)-8-isopropyl-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (G).
6-(4-(2-Fluoroethyl)piperazin-1-yl)-8-isopropyl-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (G, 23.8 mg, 0.050 mmol), TFA (2 mL), and water (0.1 mL) are combined in a sealable vessel with a stir bar, sealed, stirred, and heated at 70° C. for 1 h. Volatiles are removed on a rotary evaporator. The residue is taken up in NMP and methanol, filtered, and purified via preparatory HPLC (10-40% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are loaded onto a Strata X-C ion exchange column from Phenomenex. The column is washed sequentially with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. Eluent containing the desired product is concentrated on a rotary evaporator and dried under high vacuum to afford 6-(4-(2-fluoroethyl)piperazin-1-yl)-8-isopropyl-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (H).
[Figure (not displayed)]
To a 1,4-dioxane (5.6 mL) solution of 6-chloro-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (A, 192 mg, 0.560 mmol) is added 1-(2,2,2-trifluoroethyl)piperidin-4-ol (B, 206 mg, 1.13 mmol), cesium carbonate (367 mg, 1.13 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (105 mg, 0.169 mmol), and tris(dibenzylideneacetone)dipalladium (103 mg, 0.113 mmol) at room temperature. The mixture is bubbled with argon for 5 min, and stirred for 2 h at 100° C. The mixture is diluted with ethyl acetate and filtered through a pad of Celite. The filtrate is concentrated in vacuo. Purification by silica gel column chromatography (0-80% ethyl acetate in hexane) gave crude 3-(4-methoxybenzyl)-2-methyl-4-oxo-6-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)oxy)-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (C).
[Figure (not displayed)]
To a 1,4-dioxane (3.9 mL) solution of 6-chloro-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (1, 134 mg, 0.390 mmol) is added phenylmethanethiol (1a, 0.09 mL, 0.790 mmol), cesium carbonate (256 mg, 0.790 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (73 mg, 0.118 mmol), and tris(dibenzylideneacetone)dipalladium (72 mg, 0.0790 mmol) at room temperature. The mixture is bubbled with argon for 5 min, and stirred for 2 h at 100° C. The mixture is diluted with ethyl acetate, and washed with 5% breech in water, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration. Purification by preparative HPLC (C18 column, 15-85% acetonitrile in water+0.1% trifluoroacetic acid) gave 6-(benzylthio)-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2).
To a dichloromethane (2 mL) and water (0.4 mL) solution of 6-(benzylthio)-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2, 74 mg, 0.173 mmol) is added sulfuryl chloride (0.1 mL, 1.21 mmol) at 0° C. The mixture is stirred for 1 h at room temperature. Organic layer is separated and dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration to give crude 5-cyano-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-6-sulfonyl chloride (3).
To a dichloromethane (1.7 mL) solution of 5-cyano-3-(4-methoxybenzyl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-6-sulfonyl chloride (3, 70 mg, 0.173 mmol) is added 1-methylpiperazine (0.06 mL, 0.520 mmol) and diisopropylethylamine (0.09 mL, 0.520 mmol) at 0° C. After stirring the mixture for 1 h at room temperature, the mixture is diluted with aqueous sodium bicarbonate. Organic materials are extracted with ethyl acetate twice, dried over anhydrous magnesium sulfate, and concentrated in vacuo after filtration. Purification by preparative IPLC (C18 column, 15-60% acetonitrile in water+0.1% trifluoroacetic acid) gave 3-(4-methoxybenzyl)-2-methyl-6-((4-methylpiperazin-1-yl)sulfonyl)-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (4).
[Figure (not displayed)]
A solution of 5-bromo-2-chloro-3-fluoropyridine (1, 30.0 g, 143.6 mmol) in tetrahydrofuran (300 mL) is cooled to −78° C. and lithiumdisopropylamide (2 M in THF, 78.9 mL, 157.9 mmol) is added dropwise. This reaction mixture is stirred at −78° C. for 1 h. Then, the reaction mixture is purged with carbon dioxide gas for 15 min allowed to warm at room temperature. The reaction mixture is quenched with ammonium chloride solution and diluted with water. The aqueous layer is washed with ethyl acetate, acidified with 6 N hydrochloric acid solution, and extracted with 15% methanol in dichloromethane. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to afford 5-bromo-2-chloro-3-fluoroisonicotinic acid (2).
To solution of 5-bromo-2-chloro-3-fluoroisonicotinic acid (2, 18.0 g, 71.1 mmol) in N,N-dimethylformamide (30 mL) at 0° C., acetamidine hydrochloride (2a, 13.4 g, 142.3 mmol) is added. Then N,N-diisopropylethylamine (110 mL, 711.0 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (40.5 g, 106.6 mmol) are added and the reaction mixture is stirred at room temperature for 2 h. After this time, reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to afford crude 5-bromo-2-chloro-3-fluoro-N-(1-iminoethyl)isonicotinamide (3).
A solution of crude 5-bromo-2-chloro-3-fluoro-N-(1-iminoethyl)isonicotinamide (3, 18.0 g) in tetrahydrofuran (200 mL) is cooled to 0° C., then 60% sodium hydride in mineral oil (7.30 g NaH, 184.3 mmol) is added portionwise and the reaction mixture is stirred at room temperature for 12 h. After this time, the reaction mixture is poured into ice-cold water. The aqueous layer is washed with 5% methanol in dichloromethane, acidified with 6 N hydrochloric acid solution, and extracted with 10% methanol in dichloromethane. The organic layer from this extraction is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product which is washed with diethyl ether to afford 5-bromo-8-chloro-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (4).
To a solution of 5-bromo-8-chloro-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (4, 8.0 g, 29.3 mmol) in N,N-dimethylformamide (80.0 mL), copper(I) cyanide (4.1 g, 46.8 mmol) is added. The reaction mixture is heated at 90° C. for 3 h. After this time, the reaction mixture is cooled, diluted with water, acidified with 6 N hydrochloric acid solution, and extracted with ethyl acetate. The organic layer is concentrated to obtain the crude product which is purified by silica gel (100-200 mesh) column chromatography using 40-50% ethyl acetate in hexanes as eluent to afford 8-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (5).
To a solution of 8-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (5, 1.0 g, 4.55 mmol) in 1,4-dioxane (15.0 mL) at room temperature, 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (5a, 1.0 mL, 7.5 mmol), potassium carbonate (2.0 g, 15.0 mmol), and water (2 mL) are added. This reaction mixture is degassed with nitrogen for 10 min. Then, [1,1-bis(diphenylphospino)ferrocene] dichloropaladium(II),complex with dichloromethane (0.183 g, 0.225 mmol) is added and reaction mixture is heated at 95° C. for 12 h. After this time, the reaction mixture is cooled and concentrated under reduced pressure to obtain the crude product which is purified by silica gel (100-200 mesh) column chromatography using 10% methanol in dichloromethane as eluent to afford 2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (6).
[Figure (not displayed)]
Diethylaminosulfur trifluoride (1.44 mL, 10.4 mmol) is added to a stirred solution of 5-bromo-3-fluoropicolinaldehyde (1, 0.97 g, 4.75 mmol) in DCM (20 mL) at −78° C. under argon. The cold bath is removed, and the reaction mixture is allowed to warm to room temperature under argon for 1.5 h. The reaction mixture is poured into a stirred mixture of saturated aqueous sodium bicarbonate and ice. The resulting mixture is stirred vigorously at room temperature for 1 h to fully quench the reaction mixture. The phases are separated, and the aqueous phase extracted with dichloromethane. The combined organics are dried over sodium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (0-10% ethyl acetate in hexanes) Fractions containing the desired product are combined and concentrated on a rotary evaporator at room temperature. The residue is diluted with dry THE (5 mL) and concentrated on a rotary evaporator. The residue is dried under high vacuum for 2 min to afford 5-bromo-2-(difluoromethyl)-3-fluoropyridine (2).
[Figure (not displayed)]
A solution of 3-fluoropyridin-2-ol (1, 20.0 g, 176.9 mmol) in N,N-dimethylformamide (220.0 mL) is cooled at 0° C., bromine (10.30 mL, 194.6 mmol) is added drop wise and reaction mixture is stirred at 0° C. for 2 h. After completion reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with sodium bicarbonate and brine, dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. Crude compound is purified by column chromatography using silica gel (100-200 mesh) and 2-3% methanol in dichloromethane to afford 5-bromo-3-fluoropyridin-2-ol (2).
To a solution of 5-bromo-3-fluoropyridin-2-ol (2, 11.0 g, 57.29 mmol) in N,N-dimethylformamide (110 mL), cesium carbonate (24.59 g 74.47 mmol) and sodium 2-bromo-2,2-difluoroacetate (17.04 g, 85.93 mmol) are added and reaction mixture is heated at 55° C. After completion, reaction mixture is diluted with water and extracted with diethyl ether. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. Crude compound obtained is concentrated under reduced pressure to obtain crude product which is purified by column chromatography using silica gel (100-200 mesh) and 1-2% ethyl acetate in hexane to afford 5-bromo-2-(difluoromethoxy)-3-fluoropyridine (3).
[Figure (not displayed)]
To a solution of 2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (1, 0.16 g, 0.8 mmol) and zinc difluoromethanesulpfinate (0.472 g, 1.6 mmol) in a mixture of dichloromethane and water (4:1, 2 mL), trifluoroaceticacid (0.06 mL, 0.8 mmol) and tert-butyl hydroperoxide (0.23 mL, 2.4 mmol) are added. This mixture is stirred at room temperature for 16 h. After this time, the reaction mixture is concentrated under reduced pressure, diluted with water, and extracted with dichloromethane. The combined organic layer is washed with water and then brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) flash chromatography using 40% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 6-(difluoromethyl)-2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2).
[Figure (not displayed)]
A solution of 2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (1, 0.200 g, 0.99 mmol) and bis(((trifluoromethyl)sulfinyl)oxy)zinc (1a, 0.662 g 1.99 mmol) is stirred in chloroform (2.0 mL) and water (2.0 mL), tert-butyl hydrogen peroxide (70%) (0.38 mL, 2.99 mmol) is added at 0° C. The reaction mixture is stirred at room temperature for 15 h. After this time, the reaction mixture is diluted water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude is purified by silica gel (100-200 mesh) column chromatography using 70-80% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2,8-dimethyl-4-oxo-6-(trifluoromethyl)-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2).
[Figure (not displayed)]
To a solution of 6-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (1, 1.0 g, 4.54 mmol), in dichloromethane:water (1:1) (20.0 mL) is added 2,2,2-trifluoroacetic acid (10.4 mL, 13.63 mmol). Reaction mixture is stirred at room temperature for 15 min before the addition of phenylboronic acid (1a, 1.65 g, 13.63 mmol) and stirred for 40 min. Silver nitrate (0.154 g, 0.90 mmol) and Potassium persulfate (2.45 g, 9.09 mmol). is added and reaction mixture is stirred for 24 h at room temperature. After completion, reaction mixture is diluted with water and extracted with dichloromethane. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. The crude is washed with 30% diethyl ether in pentene to afford 6-chloro-2-methyl-4-oxo-8-phenyl-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2).
[Figure (not displayed)]
Zinc powder (<10 micron) (37.7 mg, 0.58 mmol) is weighed out in a dry 1 dram vial and placed under argon. DMA (0.4 mL) is added followed by iodine (3.6 mg, 0.014 mmol). The resulting mixture is stirred vigorously at room temperature under argon until the red color of iodine faded (5 min). 4-(bromomethyl)tetrahydro-2H-pyran (2a, 0.072 mL, 0.56 mmol) is added and the resulting mixture is sealed, stirred vigorously, and heated at 80° C. for 23 h. After cooling to room temperature the reaction mixture is placed under argon and 6-chloro-3-(4-methoxybenzyl)-2,8-dimethyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (2, 49.9 mg, 0.14 mmol) and bis(triphenylphosphine)nickel(II) dichloride (9.2 mg, 0.014 mmol) are added. The resulting mixture is stirred vigorously at room temperature under argon for 2.5 h and then at 50° C. for 2 h. The reaction mixture is diluted with NMP and methanol, filtered, and purified via preparatory HPLC (15-70% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are combined and lyophilized to dryness to afford 3-(4-methoxybenzyl)-2,8-dimethyl-4-oxo-6-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (3).
[Figure (not displayed)]
2,3-Dibromo-5-fluoropyridine (1, 3.15 g, 12.4 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (1a, 1.93 mL, 13.6 mmol), cesium carbonate (8.86 g, 27.2 mmol), 1,4-dioxane (24 mL) and water (6 mL) are combined in a 100 mL round bottom flask with a stirbar. The atmosphere in the flask is removed under vacuum and replaced with argon twice. Tetrakis(triphenylphosphine)palladium(0) (0.71 g, 0.62 mmol) is added and the atmosphere in the flask is removed under vacuum and replaced with argon twice. The resulting clear yellow reaction mixture is stirred vigorously and heated at 100° C. under argon for 12 h. After cooling to room temperature the reaction mixture is partitioned between brine and ethyl acetate. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (2-15% ethyl acetate in hexanes) to afford 3-bromo-5-fluoro-2-vinylpyridine (2).
Dimethylamine (40 wt. % in water) (34.1 mL, 108 mmol) is added to a stirred solution of 3-bromo-5-fluoro-2-vinylpyridine (2, 2.18 g, 10.8 mmol) in acetic acid (14.2 mL, 248 mmol). The resulting mixture is sealed, stirred vigorously, and heated at 110° C. for 68 h. After cooling to room temperature the reaction mixture is poured onto a stirred mixture of sodium hydroxide (9.93 g, 248 mmol) and sodium bicarbonate (4.53 g, 54.0 mmol) in ice water. The resulting mixture is extracted three times with dichloromethane. The combined organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (0-20% methanol in dichloromethane). Fractions containing the desired product are combined and concentrated on a rotary evaporator. The residue is concentrated down from THE twice and dried under high vacuum to afford 2-(3-bromo-5-fluoropyridin-2-yl)-N,N-dimethylethan-1-amine (3).
[Figure (not displayed)]
A solution of 2,3-dibromo-5-fluoropyridine (1, 10.0 g, 39.2 mmol), tributyl(1-ethoxyvinyl)stannane (1a, 15.5 mL, 43.1 mmol) and lithium chloride (4.9 g, 117.6 mmol) in N,N-dimethylformamide (100 mL) is degassed under nitrogen for 10 minutes. Then, bis(triphenylphosphine)palladium(II) dichloride (1.3 g, 1.9 mmol) is added and the mixture is heated at 100° C. for 4 h. The reaction mixture is cooled, diluted with water and extracted with diethyl ether. The combined organic layer is washed with water, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 0-2% ethyl acetate in hexane to afford 3-bromo-2-(1-ethoxyvinyl)-5-fluoropyridine (2).
A solution of 3-bromo-2-(1-ethoxyvinyl)-5-fluoropyridine (2, 5.7 g, 23.1 mmol) in dichloromethane (60 mL) is cooled to 0° C., hydrochloric acid in 1,4-dioxane (4 m, 10 mL) is added and the mixture is stirred at room temperature for 3 h. The reaction mixture is poured into ice cold water, neutralized with sodium bicarbonate and extracted with dichloromethane. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 0-5% ethyl acetate in hexane to afford 1-(3-bromo-5-fluoropyridin-2-yl)ethan-1-one (3).
A solution of 1-(3-bromo-5-fluoropyridin-2-yl)ethan-1-one (3, 3.8 g, 17.4 mmol) in dichloromethane (40 mL) is cooled to 0° C., diethylaminosulfur trifluoride (23.3 mL, 174.0 mmol) is added; the mixture is stirred at room temperature for 48 h and then heated at 40° C. for 72 h. The reaction mixture is cooled, poured into crushed ice (very slowly, in portions), neutralized with sodium bicarbonate and extracted with dichloromethane. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated. The crude is purified by column chromatography using silica gel (100-200 mesh) and 0-1% ethyl acetate in hexane to afford 3-bromo-2-(1,1-difluoroethyl)-5-fluoropyridine (4).
[Figure (not displayed)]
(Trimethylsilyl)diazomethane (2 M in diethyl ether) (19.5 mL, 39.1 mmol) is added slowly to a stirred mixture (not all dissolved) of 3,5-difluoroisonicotinic acid (1, 5.18 g, 32.6 mmol) in wet Methanol (200 mL) at 0° C. The resulting cloudy mixture is stirred vigorously at 0° C. under air. Bubbling is observed during the addition and continued for 45 min. Dichloromethane (100 mL) is added followed by more (trimethylsilyl)diazomethane (2 M in diethyl ether) (19.5 mL, 39.1 mmol). The resulting clear solution is stirred vigorously at 0° C. under air for 30 min. More (trimethylsilyl)diazomethane (2 M in diethyl ether) (19.5 mL, 39.1 mmol) is added and then more (trimethylsilyl)diazomethane (2 M in diethyl ether) (19.5 mL, 39.1 mmol) is added again until LCMS indicated complete conversion of the starting material. Volatiles are removed on a rotary evaporator. The residue is taken up in dichloromethane and purified via silica gel chromatography (0-50% ethyl acetate in hexanes) (dried under high vacuum for only a few seconds) to afford methyl 3,5-difluoroisonicotinate (2).
A solution of piperidine-4-carboxylic acid (2a 1.20 g, 9.27 mmol), ammonium persulfate (2.33 g, 10.2 mmol), and silver nitrate (590 mg, 3.47 mmol) in water (8 mL) is added to a stirred mixture of methyl 3,5-difluoroisonicotinate (2, 802 mg, 4.63 mmol) in 3% sulfuric acid in water (8 mL) at 70° C. The resulting brown mixture is heated at 70° C. with vigorous stirring for 10 min (bubbling is observed) and then cooled to room temperature. The reaction mixture is heated at 70° C. and more piperidine-4-carboxylic acid (1.20 g, 9.27 mmol), ammonium persulfate (2.33 g, 10.2 mmol), and silver nitrate (590 mg, 3.47 mmol) in water (8 mL) is added. The reaction mixture is heated at 70° C. for 10 min and then cooled to room temperature. Repeat this a total of four times. The reaction mixture is basified with potassium carbonate. All volatiles are removed on a rotary evaporator. The residue is slurried with 20% methanol in dichloromethane and filtered through Celite. The filter cake is washed thoroughly with 20% methanol in dichloromethane. The filtrate is concentrated on a rotary evaporator with silica gel and purified via silica gel chromatography (0-20% methanol in dichloromethane) to afford methyl 3,5-difluoro-2-(piperidin-4-yl)isonicotinate (3).
2,2,2-Trifluoroethyl trifluoromethanesulfonate (3a, 1.05 mL, 7.32 mmol) is added to a stirred solution of methyl 3,5-difluoro-2-(piperidin-4-yl)isonicotinate (3, 625 mg, 2.44 mmol) and N,N-diisopropylethylamine (3.40 mL, 19.5 mmol) in NMP (10 mL) at room temperature under argon. The resulting mixture is stirred at room temperature under argon for 3 h. The reaction mixture is diluted with ethyl acetate, washed three times with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (0-50% ethyl acetate in hexanes) to afford methyl 3,5-difluoro-2-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)isonicotinate (4).
Methyl 3,5-difluoro-2-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)isonicotinate (4, 505 mg, 1.49 mmol), trimethyltin hydroxide (1.08 g, 5.97 mmol), and DCE (10 mL) are combined in a 100 mL round bottom flask with a stirbar. The resulting mixture is stirred vigorously and heated at 80° C. under a reflux condenser under argon for 1 h and then at 85° C. for 3 h. Volatiles are removed on a rotary evaporator. The residue is taken up in 20% methanol in dichloromethane and purified via silica gel chromatography (0-20% methanol in dichloromethane) to afford 3,5-difluoro-2-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)isonicotinic acid (5).
[Figure (not displayed)]
Lithium bis(trimethylsilyl)amide (1M in toluene) (2.23 mL, 2.23 mmol) is added slowly to a stirred solution of tert-butyl 4-cyanopiperidine-1-carboxylate (1, 469 mg, 2.23 mmol) and 3-bromo-2,5-difluoropyridine (2, 433 mg, 2.23 mmol) in toluene (5 mL) at −78° C. under argon. The cold bath is removed and the resulting orange solution is allowed to warm to room temperature with stirring under argon and allowed to stir at room temperature for 2 h. 0.2 M HCl in water (22.3 mL, 4.46 mmol) is added with vigorous stirring. The resulting mixture is extracted with ethyl acetate. The organics are washed with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (0-50% ethyl acetate in hexanes) to afford tert-butyl 4-(3-bromo-5-fluoropyridin-2-yl)-4-cyanopiperidine-1-carboxylate (3).
n-Butyllithium (2.5 M in hexane) (0.48 mL, 1.20 mmol) is added to a stirred solution of diisopropylamine (0.18 mL, 1.30 mmol) in THF (4 mL) at 0° C. under argon. The resulting light yellow solution is stirred for 10 min at 0° C. and then added slowly to a stirred solution of tert-butyl 4-(3-bromo-5-fluoropyridin-2-yl)-4-cyanopiperidine-1-carboxylate (3, 401 mg, 1.04 mmol) in THF (7 mL) at −78° C. under argon. The resulting orange reaction mixture is stirred at −78° C. under argon for 30 min and then carbon dioxide gas is bubbled in for ˜1 min. (orange color fades) After 10 min 0.1 N sodium hydroxide in water (1 mL) is added to quench the reaction mixture. The resulting mixture is partitioned between 0.1 N sodium hydroxide in water (20 mL) and diethyl ether. The organics are extracted twice more with 0.1 N sodium hydroxide in water (5 mL). The organics are discarded. The water layer is acidified with 1 N HCl in water and then extracted four times with ethyl acetate. The organics are washed with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and dried under high vacuum to afford 3-bromo-2-(1-(tert-butoxycarbonyl)-4-cyanopiperidin-4-yl)-5-fluoroisonicotinic acid (4).
HATU (366 mg, 0.964 mmol) is added to a stirred solution of 3-bromo-2-(1-(tert-butoxycarbonyl)-4-cyanopiperidin-4-yl)-5-fluoroisonicotinic acid (4, 393 mg, 0.918 mmol) in DMF (6 mL) at room temperature under argon. After 2 min N,N-diisopropylethylamine (0.19 mL, 1.10 mmol) is added. The resulting orange mixture is stirred at room temperature under argon for 20 min. A solution of acetamidine hydrochloride (174 mg, 1.84 mmol) and N,N-diisopropylethylamine (0.80 mL, 4.59 mmol) in DMF (3 mL) (this is heated with a heat gun and sonicated to get all of the acetamidine dissolved) is added. The resulting orange mixture is stirred vigorously at room temperature under argon for 2 h. The reaction mixture is diluted with ethyl acetate, washed four times with brine, dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. Dry THE (10 mL) is added and volatiles are removed on a rotary evaporator again. The residue is dried under high vacuum for 10 min. The residue is dissolved with stirring in THE (15 mL) and cooled to 0° C. under argon. Sodium hydride (44.1 mg, 1.84 mmol) is added. The cold bath is removed and the resulting cloudy orange mixture is stirred vigorously at room temperature under argon for 2.5 h. A solution of ammonium chloride (147 mg, 2.75 mmol) in water (2 mL) is added and then the resulting mixture is partitioned between ethyl acetate and brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (20-100% ethyl acetate in hexanes) to afford tert-butyl 4-(5-bromo-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-6-yl)-4-cyanopiperidine-1-carboxylate (5).
tert-Butyl 4-(5-bromo-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-6-yl)-4-cyanopiperidine-1-carboxylate (5, 313 mg, 0.698 mmol), ethanol (17 mL), and lithium hydroxide (1 M in water) (6.98 mL, 6.98 mmol) are combined in a sealable vessel with a stirbar. The resulting mixture is sealed, stirred vigorously, and heated at 120° C. with an oil bath for 44 h. After cooling to room temperature the reaction mixture is diluted with methanol and concentrated on a rotary evaporator. The residue is taken up in NMP, methanol, and acetic acid (0.60 mL, 10.5 mmol), filtered, and purified via preparatory HPLC (15-60% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are combined and lyophilized to dryness to afford tert-butyl 4-(5-bromo-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-6-yl)-4-carbamoylpiperidine-1-carboxylate (6).
A stirred mixture of tert-butyl 4-(5-bromo-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-6-yl)-4-carbamoylpiperidine-1-carboxylate TFA salt (6, 186 mg, 0.321 mmol) in 6 M HCl in water (7 mL) is heated at 140° C. with an oil bath for 2 min and then sealed, stirred vigorously, and heated at 140° C. with an oil bath for 2 h. More 6 M HCl in water (3 mL) is added and heating at 140° C. with an oil bath continued for another 21 h. After cooling to room temperature the reaction mixture is diluted with methanol, filtered, and purified via preparatory HPLC (5-18% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are loaded onto a Strata X-C ion exchange column from Phenomenex. The column is washed sequentially with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. Eluent containing the desired product is concentrated on a rotary evaporator and dried under high vacuum to afford 5-bromo-2-methyl-6-(piperidin-4-yl)pyrido[3,4-d]pyrimidin-4(3H)-one (7).
[Figure (not displayed)]
To a solution of 5-fluoropyridin-2-ol (1, 9.00 g, 0.079 mol) in tetrahydrofuran (290 mL) at 0° C., Trimethylphenylammonium tribromide (29.9 g, 0.079 mol) is added slowly and reaction mixture is stirred at room temperature for 16 h. After 16 h, the reaction mixture is partitioned between ethyl acetate and water. Aqueous layer is separated and re-extracted with ethyl acetate. The combined organic layer is washed with 5% sodium metabisulphite solution, saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated to get crude product. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 0-30% ethyl acetate in hexanes afford 3-bromo-5-fluoropyridin-2-ol (2) as off white solid. Yield: 4.90 g, 27%; MS (ESI) m/z 189.99 [M−1]−.
To a solution of 3-bromo-5-fluoropyridin-2-ol (2, 4.10 g, 0.021 mol) in N,N-dimethylformamide (40 mL), cesium carbonate (3.48 g, 0.031 mol) and sodium 2-bromo-2,2-difluoroacetate (2a, 5.05 g, 0.025 mmol) are added and the reaction mixture is heated at 70° C. for 4 h. After completion, reaction mixture cooled down and partitioned between diethyl ether and water. Aqueous layer is separated and re-extracted with diethyl ether. The combined organic layer is washed with water, saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated to get crude product. The crude product is purified by column chromatography using silica gel (100-200 mesh) and hexane as eluent to afford 3-bromo-2-(difluoromethoxy)-5-fluoropyridine (3)
[Figure (not displayed)]
[Figure (not displayed)]
A solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (B, 1.1 equiv.) and 1,1,1-triethoxyethane (C, 0.7 M) is stirred and heated at 90° C. for 2 h. methyl 4-aminothiophene-3-carboxylate (A, 1 equiv.) is added portionwise at 90° C. under argon atmosphere and heating at 90° C. continued for 6 h. The reaction mixture is cooled to room temperature, water added, and the mixture extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product is triturated with diethyl ether to afford methyl 4-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)thiophene-3-carboxylate (D).
A solution of methyl 4-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)thiophene-3-carboxylate (D, 1 equiv.) in Dowtherm A (0.5 M), is heated at 235° C. for 4 h. After completion, the reaction mass is cooled to room temperature, the precipitated solid isolated by filtration and dried in vacuo. The solid obtained is washed with diethyl ether to afford methyl 7-hydroxy-5-methylthieno[3,2-b]pyridine-3-carboxylate (E).
To a solution of methyl 7-hydroxy-5-methylthieno[3,2-b]pyridine-3-carboxylate (E, 1 equiv.) in 1,2-dichloroethane (0.22 M) are added phosphoryl trichloride (3 equiv.) and a catalytic amount of N,N-dimethylformamide at room temperature and the reaction mixture heated at 90° C. for 6 h. The reaction mixture is concentrated under reduced pressure, diluted with ice cold water, and the solution basified with 10% aqueous sodium hydroxide solution to pH ˜7-8 followed by extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to afford methyl 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylate (F1).
To a solution of methyl 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylate (F1, 1 equiv.) in mixture of methanol (1.7 M), water (1.7 M) and tetrahydrofuran (0.64 M) is added lithium hydroxide monohydrate (2 equiv.) at room temperature and the resulting mixture is stirred for 2 h. The solid is filtered, the filtrate is concentrated and combined with the solid. The combined solids are acidified with saturated citric acid solution (up to pH=1) and filtered. The resulting solid is washed with methanol followed by diethyl ether and dried under high vacuum to afford 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (F2).
To a solution of 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (F2, 1 equiv.) in tert-butyl alcohol (0.4 M) is added 4-dimethylaminopyridine (1 equiv.) and Boc-anhydride (3 equiv.) at room temperature. The mixture is stirred for 48 h at 90° C. and the reaction mixture is concentrated under reduced pressure. The crude product is purified by column chromatography over silica gel to afford tert-butyl 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylate (F3).
To a solution of tert-butyl 7-chloro-5-methylthieno[3,2-b]pyridine-3-carboxylate (F3, 1 equiv.) and (5-chloro-2-hydroxyphenyl)boronic acid (G, 1.2 equiv.), in 1,4-dioxane (0.5 M) and water (1.2 M) is added potassium carbonate solution (2 equiv.) at room temperature and the reaction mixture degassed with argon for 20 minutes. [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.05 equiv.) is added and mixture heated at 90° C. for 2 h. The reaction mixture is cooled to room temperature and filtered and the solid, washed with water followed by methanol, and dried under vacuum to afford tert-butyl 7-(5-chloro-2-hydroxyphenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (H).
To a solution of tert-butyl 7-(5-chloro-2-hydroxyphenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (H, 1 equiv.) in acetone (0.28 M) are added potassium carbonate (3.5 equiv.) and 1,2-dibromoethane (I, 5.0 equiv.) at room temperature and the reaction mixture heated at 40° C. for 12 h. An additional 5.0 equiv. of 1,2-dibromoethane is then added at room temperature and the mixture heated to 45° C. The reaction mixture is filtered through a sintered funnel, washed with acetone, and the filtrate concentrated and purified by column chromatography to afford tert-butyl 7-(2-(2-bromoethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (J).
[Figure (not displayed)]
A solution of 2-bromo-4-chloro-1-iodobenzene (A, 1 equiv.) and prop-2-yn-1-ol (B, 1.3 equiv.) in triethylamine (0.3 M) is degassed with argon for 10 min. Copper(I) iodide (0.15 equiv.) and bis(triphenylphosphine)palladium chloride (0.08 equiv.) are added and the reaction mixture stirred at room temperature for 16 h. The reaction mass is concentrated under reduced pressure and the crude compound purified by Combi-flash to afford 3-(2-bromo-4-chlorophenyl)prop-2-yn-1-ol (C).
To a solution of 3-(2-bromo-4-chlorophenyl)prop-2-yn-1-ol (C, 1 equiv.) in tetrahydrofuran (0.8 M) are added imidazole (3 equiv.), 4-dimethylaminopyridine (0.045 equiv.) and tert-butyldimethylchlorosilane (1.2 equiv.) at room temperature and the reaction mixture stirred for 24 h. The reaction mass is diluted with water, extracted with ethyl acetate and the organic layer separated, dried over anhydrous sodium sulphate, and purified by Combi-flash to afford ((3-(2-bromo-4-chlorophenyl)prop-2-yn-1-yl)oxy)(tert-butyl)dimethylsilane (D).
To a solution of ((3-(2-bromo-4-chlorophenyl)prop-2-yn-1-yl)oxy)(tert-butyl)dimethylsilane (D, 1 equiv.) in tetrahydrofuran (0.14 M) is added dropwise n-butyllithium (1.23 M in hexanes, 1.3 equiv.) at −78° C. and the mixture stirred at −78° C. for 1 h. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (E, 1.2 equiv.) is added dropwise at −78° C. and stirring continued for 1 h. The reaction is quenched with chilled water, extracted with ethyl acetate, and the organic layer separated, dried over anhydrous sodium sulphate, concentrated, and purified by Combi-flash to afford tert-butyl((3-(4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)prop-2-yn-1-yl)oxy)dimethylsilane (F).
[Figure (not displayed)]
To a solution of methyl 7-(2-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) in tetrahydrofuran (0.21 M) is added tetra-n-butylammonium fluoride (1.2 equiv.) at room temperature and the mixture stirred for 2 h. The reaction mass is diluted with ethyl acetate, washed with cold water and the organic layer separated, dried over anhydrous sodium sulphate, concentrated, and triturated with diethyl ether to afford methyl 7-(5-chloro-2-(3-hydroxyprop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (B).
To a solution of methyl 7-(5-chloro-2-(3-hydroxyprop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (B, 1 equiv.) in dichloromethane (10.0 mL) is added triphenylphosphine (1.5 equiv.) at room temperature and the reaction mixture cooled to 0° C. Carbontetrabromide (1.5 equiv.) is added and the reaction mixture stirred for 3 h at room temperature. The reaction mass is concentrated and purified by Combi-flash to afford methyl 7-(2-(3-bromoprop-1-yn-1-yl)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
A solution of methyl 7-hydroxy-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) and phosphorous oxybromide (10 equiv.) in 1,2 dichloroethane (0.45 M) is heated at 80° C. for 16 h. The reaction mixture is cooled to room temperature, quenched with aqueous solution of sodium bicarbonate, extracted with dichloromethane, and the combined organic layer washed with brine, dried over anhydrous sodium sulphate, filtered, concentrated, and purified by column chromatography to afford methyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (B).
A solution of methyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (B, 1 equiv.) and lithium hydroxide (3 equiv.) in methanol:tetrahydrofuran:water solvent mixture (1:2:1, 0.25 M) is stirred at room temperature for 16 h. The reaction is diluted with water, cooled to 0° C. and acidified with 1 N hydrochloric acid to pH ˜5. The precipitate is filtered, washed with pentane and dried to afford 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C)
To a solution of 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C, 1 equiv.) and methanesulfonamide (D, 1.5 equiv.) in dichloromethane (0.16 M), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (2 equiv.) and N,N-dimethylpyridin-4-amine (2.5 equiv.) are added at room temperature and the mixture stirred for 16 h. The reaction is diluted with water, cooled to 0° C., acidified with 1 N hydrochloric acid to pH ˜2 and extracted with dichloromethane. The combined organic layer is dried over anhydrous sodium sulphate, concentrated, and purified by column chromatography to afford 7-bromo-5-methyl-N-(methylsulfonyl)thieno[3,2-b]pyridine-3-carboxamide (E).
[Figure (not displayed)]
To a solution of tert-butyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 1.50 g, 4.5 mmol) in 1,4-dioxane is added selenium dioxide (0.55 g, 5.02 mmol) and reaction mixture is heated at 95° C. for 8 h. After completion, the reaction mixture is filtered over Celite bed and washed with ethyl acetate. The filtrate obtained is concentrated under reduced pressure to get crude product. The crude product obtained is purified by column chromatography using silica gel (100-200 mesh) and 10% ethyl acetate in hexanes to afford tert-butyl 7-bromo-5-formylthieno[3,2-b]pyridine-3-carboxylate (2).
To a solution of tert-butyl 7-bromo-5-formylthieno[3,2-b]pyridine-3-carboxylate (2, 0.55 g, 1.62 mmol) in methanol (6 mL) at 0° C. is added sodium borohydride (0.12 g, 3.25 mmol) and reaction mixture is stirred at same temperature for 1 hour. After completion, the reaction mixture is quenched with ice water and concentrated under reduced pressure. The crude material is dissolved in ethyl acetate, washed with water, brine solution, dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. The crude compound obtained is purified by column chromatography using silica gel (100-200 mesh) and 20% ethyl acetate in hexanes to afford tert-butyl 7-bromo-5-(hydroxymethyl)thieno[3,2-b]pyridine-3-carboxylate (3).
To a solution of tert-butyl 7-bromo-5-(hydroxymethyl)thieno[3,2-b]pyridine-3-carboxylate (3, 0.325 g, 0.94 mmol) in dichloromethane (5 mL) at −78° C., DAST (0.18 mL, 1.41 mmol) is added and reaction mixture is stirred at −78° C. for 1 hour. After completion, reaction mixture is quenched with ice cold water and extracted with dichloromethane. The organic layer is washed saturated solution of sodium bicarbonate, dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. The crude compound obtained is purified by column chromatography using silica gel (100-200 mesh) and 10% ethyl acetate in hexane to get tert-butyl 7-bromo-5-(fluoromethyl)thieno[3,2-b]pyridine-3-carboxylate (4).
[Figure (not displayed)]
A solution of tert-butyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 500.0 mg, 1.523 mmol), Azobisisobutyronitrile (24.98 mg, 0.152 mmol) and N-Bromosuccinimide (271.13 mg, 1.523 mmol) in carbon tetrachloride (10 mL) is stirred at 90° C. for 5 h. After completion, reaction mixture is concentrated under reduced pressure and is diluted with dichloromethane and silica gel is added. The solvent is evaporated. The crude silica mixture is purified by Isco column chromatography using 0-10% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-bromo-5-(bromomethyl)thieno[3,2-b]pyridine-3-carboxylate (2)
To a stirred solution of tert-butyl 7-bromo-5-(bromomethyl)thieno[3,2-b]pyridine-3-carboxylate (2, 0.200 g, 0.491 mmol) in methanol (0.2 mL) and N-methylpyrrolidone (2.0 mL) is added cesium carbonate (0.480 g, 1.474 mmol) at RT and reaction mixture is stirred at room temperature for 8 h. After completion, the reaction mixture is diluted with dichloromethane and then silica gel is added. The solvent is then evaporated and the free flow silica gel is then loaded on the column and purified via silica gel chromatography eluting with methanol in dichloromethane to afford tert-butyl 7-bromo-5-(methoxymethyl)thieno[3,2-b]pyridine-3-carboxylate (3).
[Figure (not displayed)]
[Figure (not displayed)]
To a stirred solution of 4-methoxybenzyl alcohol (8.1 g, 59.1 mmol) in N,N-dimethylformamide (100 mL) at 0° C., sodium hydride (3.1 g, 65.0 mmol) is added. This reaction mixture is stirred at 0° C. for 30 min. Then, 7-chlorothieno[3,2-b]pyridine (1, 10 g, 59.1 mmol) is added at 0° C. and reaction mixture is stirred for 16 h at room temperature. After this time, the mixture is poured into ice. The resulting precipitate is collected by filtration and dried under reduced pressure to afford 7-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine (2).
To a stirred solution of 7-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine (2, 8.0 g, 29.5 mmol) in dry tetrahydrofuran (250 mL), n-butyllithium (2.3 M in hexanes, 38.0 mL, 64.9 mmol) is added dropwise at −78° C. This reaction mixture is stirred at the same temperature for 45 min. Then, carbon tetrabromide (9.7 g, 29.5 mmol) is added at −78° C. and the mixture is stirred at same temperature for 1 h. After this time, the reaction is quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) column chromatography using 15% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-bromo-7-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine (3).
A solution of 2-bromo-7-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine (3, 6.5 g, 18.62 mmol) in a mixture of trifluoroacetic acid and dichloromethane (1:1, 40 mL) is stirred at room temperature for 8 h. After this time, the reaction mixture is concentrated under reduced pressure. The crude product is recrystallized with ether and pentanes to afford 2-bromothieno[3,2-b]pyridin-7-ol (4).
To a solution of 2-bromothieno[3,2-b]pyridin-7-ol (4, 3.5 g, 15.28 mmol) in methanol (30 mL), 30% sodium methoxide in methanol (14.0 g, in methanol, 76.4 mmol) and copper(I) bromide (0.200 g, 1.5 mmol) are added. This reaction mixture is stirred at 120° C. for 30 h. After this time, the reaction mixture is concentrated under reduced pressure, acidified with 2 N hydrochloric acid to pH-6, and extracted with 10% methanol in dichloromethane. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to afford 2-methoxythieno[3,2-b]pyridin-7-ol (5).
A mixture of 2-methoxythieno[3,2-b]pyridin-7-ol (5, 1.7 g, 9.39 mmol) and phosphoryl chloride (10 mL) is heated and stirred at 900° C. for 6 h. After this time, the reaction mixture is quenched with ice, treated with aqueous 50% sodium hydroxide solution, and extracted with ethyl acetate. The organic layer is washed with water and then saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product is purified by Combiflash using 30% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 7-chloro-2-methoxythieno[3,2-b]pyridine (6).
To a solution of 3-bromo-7-chloro-2-methoxythieno[3,2-b]pyridine (6, 0.8 g, 4.02 mmol) in N,N-dimethylformamide (10 mL) at room temperature, N-bromosuccinimide (1.4 g, 8.04 mmol) is added. This reaction mixture is stirred for 30 min. Then, the reaction mixture is poured into ice and extracted with ethyl acetate. The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 3-bromo-7-chloro-2-methoxythieno[3,2-b]pyridine (7).
To a stirred solution of 3-bromo-7-chloro-2-methoxythieno[3,2-b]pyridine (7, 0.7 g, 2.52 mmol) in dry tetrahydrofuran (10 mL), n-butyllithium (2.3 M in hexanes, 1.97 mL, 4.54 mmol) is added dropwise at −78° C. This reaction mixture is stirred at the same temperature for 45 min. Dry carbon dioxide gas is bubbled through the reaction mixture, which is slowly warmed up to room temperature and stirred for 16 h. The reaction mixture is quenched with 10% aqueous citric acid solution and extracted with 10% methanol in dichloromethane. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to afford 7-chloro-2-methoxythieno[3,2-b]pyridine-3-carboxylic acid (8).
To a solution of 7-chloro-2-methoxythieno[3,2-b]pyridine-3-carboxylic acid (8, 0.5 g, 2.05 mmol) in N,N-dimethylformamide (5.0 mL) at room temperature, potassium carbonate (0.85 g, 6.17 mmol) and methyl iodide (0.32 g, 2.26 mmol) are added. This reaction mixture is stirred for 16 h. After this time, the reaction mixture is poured into ice and extracted with ethyl acetate. The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 2% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford methyl 7-chloro-2-methoxythieno[3,2-b]pyridine-3-carboxylate (9).
[Figure (not displayed)]
To a stirred solution of 3-bromobenzoic acid (1, 100.0 g, 497.5 mmol) in N,N-dimethylformamide (800 mL), carbodiimidazole (112.9 gm, 696.5 mmol) is added at room temperature and the reaction mixture is heated and stirred at 50° C. for 1 h. 1,8-Diazabicyclo[5.4.0]undec-7-ene (105.8 gm, 696.5 mmol) and tert-butanol (184.37 gm, 2487.5 mmol) are added at 50° C. and the reaction mixture is continued to stir at 50° C. for 16 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product obtained is purified by column chromatography using 100-200 silica gel and 2% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 3-bromobenzoate (2).
A stirred solution of tert-butyl 3-bromobenzoate (2, 113.0 g, 439.4 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (3, 167.43 gm, 659.1 mmol) and potassium acetate (107.65 gm, 1098.5 mmol) in dioxane (600 mL) is degassed with argon for 30 min. Then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) is added and the reaction mixture is heated and stirred at 85° C. for 16 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the crude mass. This crude compound is purified by column chromatography using 100-200 silica gel and 3% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (4).
A stirred solution of 4-chloro-2-iodophenol (5, 60.0 g, 235.8 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (4, 100.37 g, 330.1 mmol) and potassium carbonate (97.76 g, 707.4 mmol) in a mixture of dioxane and water (4:1, 1.0 Lit) is degassed with argon for 30 min. Palladium(II)bis(triphenylphosphine) dichloride is added at room temperature and stirred the reaction mixture at 100° C. for 6 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude compound obtained is purified by column chromatography using 100-200 silica gel and 4% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-carboxylate (6).
To a stirred solution of tert-butyl 5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-carboxylate (6, 55.0 g, 180.5 mmol) in 1 N aqueous solution of sodium hydroxide (1.1 Lit), tetrabutylammoniumbromide (8.72 g, 27.07 mmol) and potassium iodide (4.49 g, 27.07 mmol) are added at room temperature and the reaction mass is heated to 90° C. 1,2-Dibromoethane (7, 57.82 mL, 667.89 mmol) is added slowly at 90° C. and the reaction mixture is stirred at 90° C. for 16 h. After completion, the reaction mass is extracted with dichloromethane. The organic layer is dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude mass. The crude compound is purified by column chromatography using 100-200 silica gel and 2% ethyl acetate in hexanes to afford tert-butyl 2′-(2-bromoethoxy)-5′-chloro-[1,1′-biphenyl]-3-carboxylate (8).
[Figure (not displayed)]
To a stirred solution of ethyl 2-(diethoxyphosphoryl)acetate (2, 23.01 g, 102.7 mmol) in tetrahydrofuran (100 mL) at 0° C., sodium hydride (60%) (5.47 g, 136.9 mmol) is added and the reaction mixture is stirred at 0° C. for 1 h. 2-bromo-4-chlorobenzaldehyde (1, 15.0 g, 68.4 mmol) in tetrahydrofuran (3 mL) is added slowly and the reaction mixture is stirred at 0° C. for 2 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get the crude mass. The crude material is purified by Combi-flash using 3% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford ethyl (E)-3-(2-bromo-4-chlorophenyl)acrylate (3).
To a stirred solution of ethyl (E)-3-(2-bromo-4-chlorophenyl)acrylate (3, 2.0 g, 17.3 mmol) in dichloromethane (15.0 mL), diisobutylaluminium hydride (1 M in toluene) (31.1 mL, 31.1 mmol) is added and stirred at −78° C. for 1 h. The reaction mixture is slowly allowed to room temperature and stirred for 1 h. After completion, the reaction mass is quenched with aqueous ammonium chloride solution and extracted with dichloromethane. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get the crude mass which is purified by Combi-flash using 13% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford (E)-3-(2-bromo-4-chlorophenyl)prop-2-en-1-ol (4).
A stirred solution of (E)-3-(2-bromo-4-chlorophenyl)prop-2-en-1-ol (4, 1.5 g, 6.07 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (5, 2.03 g, 6.68 mmol), and potassium carbonate (2.51 g, 18.2 mmol) in a mixture of dioxane and water (4:1) (24.0 mL) is degassed with argon for 30 min. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.222 g, 0.3 mmol) is added and the reaction mixture is heated at 90° C. for 12 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get the crude mass. The crude compound is purified by Combi-flash using 15% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl (E)-5′-chloro-2′-(3-hydroxyprop-1-en-1-yl)-[1,1′-biphenyl]-3-carboxylate (6).
To a stirred solution of tert-butyl (E)-5′-chloro-2′-(3-hydroxyprop-1-en-1-yl)-[1,1′-biphenyl]-3-carboxylate (6, 1.5 g, 4.34 mmol) and triethylamine (1.82 mL, 13.04 mmol) in dichloromethane at 0° C., methanesulfonyl chloride (0.67 mL, 8.69 mmol) is added and the reaction mixture is slowly allowed to room temperature and stirred for 16 h. After completion, the reaction mass is quenched with water and extracted with dichloromethane. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get the crude material. The crude compound is purified by Combi-flash using 10% ethyl acetate in hexanes as eluent to afford tert-butyl (E)-5′-chloro-2′-(3-chloroprop-1-en-1-yl)-[1,1′-biphenyl]-3-carboxylate (7).
[Figure (not displayed)]
A stirred solution of 2-bromo-4-chloro-1-iodobenzene (1, 1.0 g, 3.15 mmol), prop-2-yn-1-ol (2, 0.2 mL, 3.47 mmol) & copper(I) iodide (0.024 g, 0.126 mmol) in triethyl amine (30 mL) is degassed with argon for 20 min. Dichlorobis(triphenylphosphine)palladium(II) (0.110 g, 0.15 mmol) is added and the reaction mixture is stirred at room temperature for 16 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the crude material. This crude compound is purified by Combi-flash using 10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 3-(2-bromo-4-chlorophenyl)prop-2-yn-1-ol (3) as yellow solid. Yield: 0.725 g, 93%, MS no ionization.
To a stirred solution of 3-(2-bromo-4-chlorophenyl)prop-2-yn-1-ol (3, 0.72 g, 2.93 mmol) in dichloromethane (10 mL), thionyl chloride (0.85 mL, 11.75 mmol) is added at 0° C. and the reaction mixture is heated and stirred at 50° C. for 16 h. After completion, the reaction mass concentrated under reduced pressure to obtain the crude which is purified by Combi-flash using 3% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-bromo-4-chloro-1-(3-chloroprop-1-yn-1-yl) benzene (4)
[Figure (not displayed)]
To a solution of 6-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (A, 1 equiv.) in N,N-dimethylformamide (0.2 M solution) is added potassium carbonate (3 equiv.) and tert-butyl 7-(2-(2-bromoethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (B, 1 equiv.) and the reaction mixture is heated at 60° C. for 16 h. The reaction mixture is then cooled, diluted with water, and extracted 2× with ethyl acetate. The combined organic layer is washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel column chromatography affords tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C).
To a solution of 6-chloro-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (A, 1 equiv.) in N,N-dimethylformamide (0.14 M) is added tert-butyl 7-(2-(2-bromoethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (B, 1.3 equiv.), potassium iodide (0.2 equiv.), and ground potassium carbonate (3 equiv.) at room temperature. The mixture is stirred for 16 h at 50° C., diluted with water, and extracted 2× with ethyl acetate with ethyl acetate. The combined organic layer is washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Purification by silica gel column chromatography gives tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
[Figure (not displayed)]
To a solution of 3-bromo-5-fluoroisonicotinic acid (A, 5.0 g, 21.92 mmol) in dimethylformamide (15 mL), potassium carbonate (6.07 g, 43.84 mmol) and iodomethane (2.05 mL, 32.88 mmol) are added at room temperature and stirred the reaction mixture for 2 h at room temperature. After completion, the reaction mass is diluted with ethyl acetate and washed with cold water. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated to give crude. The crude is purified by flash chromatography eluting the compound with ethyl acetate in hexanes (1-10%). The desired fractions are concentrated under reduced pressure to afford methyl 3-bromo-5-fluoroisonicotinate (B).
To a solution of methyl 3-bromo-5-fluoroisonicotinate (B, 4.0 g, 17.17 mmol) in dimethylformamide (15 mL), potassium carbonate (7.0 g, 51.51 mmol) is added followed by drop wise addition of 4-methoxy benzyl amine (3.52 mL, 25.0 mmol at room temperature The reaction mixture is stirred for 16 h at 50° C. After completion, the reaction mass is diluted with ethyl acetate and washed with cold water. The organic layer is separated and dried over anhydrous sodium sulphate, filtered and concentrated to give crude. The crude is purified by flash column chromatography eluting the compound with ethyl acetate in hexanes (10-20%). The desired fractions are concentrated under reduced pressure to afford methyl 3-bromo-5-((4-methoxybenzyl)amino)isonicotinate (C).
To a solution of methyl 3-bromo-5-((4-methoxybenzyl)amino)isonicotinate (C, 2.8 g, 8.0 mmol) in methanol (5.0 mL) and water (5.0 mL) is added sodium hydroxide (0.64 g, 26.0 mmol) and stirred the reaction mixture for 6 h at room temperature. After completion, the reaction mass is concentrated to evaporate methanol. The aqueous layer is cooled to 0° C. and acidified with 2 N hydrochloric acid (pH ˜4). The precipitated solid is filtered and dried to afford 3-bromo-5-((4-methoxybenzyl)amino)isonicotinic acid (D).
To a solution of 3-bromo-5-((4-methoxybenzyl)amino)isonicotinic acid (D, 0.9 g, 26.0 mmol) in dimethylformamide (15 mL), methyl 7-(2-(2-aminoethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (E, 1.16 g, 32.0 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (1.48 g, 39.0 mmol) are added at 0° C. Diisopropylethylamine is added drop wise at 0° C. and stirred the reaction mixture at room temperature for 3 h. After completion, the reaction mass is diluted with ethyl acetate and washed with cold water. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give crude. The crude is purified by flash column chromatography eluting the compound with methanol in dichloromethane (2-5%). The desired fractions are concentrated under reduced pressure to afford methyl 7-(2-(2-(3-bromo-5-((4-methoxybenzyl)amino)isonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (F).
To a solution of methyl 7-(2-(2-(3-bromo-5-((4-methoxybenzyl)amino)isonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (F, 1.8 g, 26.0 mmol) in dichloromethane (10 mL) is added triflouroacetic acid (10 mL) at 0° C. and is stirred the reaction mixture at room temperature for 2 h. After completion, the reaction mass is concentrated to give crude. The crude is triturated with diethyl ether to afford methyl 7-(2-(2-(3-amino-5-bromoisonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (G).
To a solution of methyl 7-(2-(2-(3-amino-5-bromoisonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (G, 1.2 g, 2.1 mmol) in tetrahydofuran (10 mL), 2,2-difluoroacetic anhydride (H, 0.26 mL, 2.1 mmol) is added at 0° C. and stirred the reaction mixture at room temperature for 1 h. After completion, the reaction mass is concentrated to give crude. The crude is purified by washing and triturating with diethyl ether to afford methyl 7-(2-(2-(3-bromo-5-(2,2-difluoroacetamido)isonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (I).
A solution of methyl 7-(2-(2-(3-bromo-5-(2,2-difluoroacetamido)isonicotinamido)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (I, 1.0 g, 1.56 mmol) in acetic acid (10 mL) is heated and stirred at 110° C. for 24 h. After completion, acetic acid is removed under reduced pressure to give crude. The crude is purified by flash column chromatography eluting the compound with ethyl acetate in hexanes (50-70%). The desired fractions are concentrated under reduced pressure to afford methyl 7-(2-(2-(5-bromo-2-(difluoromethyl)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (J).
[Figure (not displayed)]
To a solution of cyclopropanol (B, 2.5 equiv.) in tetrahydrofuran (0.6 M), sodium hydride (3 equiv.) is added and the reaction mixture stirred at 0° C. for 10 min. tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) is added to the reaction mixture at room temperature and heated at 120° C. for 6 h. The reaction mixture is cooled to room temperature, diluted with water, extracted with ethyl acetate, and the ethyl acetate layer dried over sodium sulfate, concentrated, and purified over a plug of silica gel to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-cyclopropoxy-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C1).
To a solution of tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-cyclopropoxy-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C1, 1 equiv.) in dichloromethane (0.1 M), triflouroacetic acid (0.1 M) is added at 0° C. The reaction is slowly brought to room temperature and stirred for 16 h. The reaction is concentrated under reduced pressure, washed with diethyl ether, and purified by preparative HPLC to afford 7-(5-chloro-2-(2-(5-cyano-6-cyclopropoxy-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C2)
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.), and azetidin-3-ol hydrochloride (B, 2 equiv.) in DMF (0.16 M), potassium carbonate (5 equiv.) is added at room temperature followed by heating at 100° C. with stirring for 16 h. The reaction mixture is diluted with water, extracted with ethyl acetate, and the organic layers washed with water and brine solution, dried over sodium sulfate, concentrated, and purified by flash chromatography to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(3-hydroxyazetidin-1-yl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
A solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.), and cesium hydroxide (3 equiv.) in 1,4-dioxane (0.12 M) is degassed under nitrogen for 5 minutes. Tris(dibenzylideneacetone)dipalladium(0) (0.05 equiv.) and 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole (0.03 equiv.) are added and the mixture heated at 90° C. for 16 h. The reaction mixture is cooled, diluted with water, extracted with ethyl acetate, and the combined organic layer, dried over anhydrous sodium sulphate, filtered and concentrated to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-hydroxy-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (B).
[Figure (not displayed)]
A solution tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) in methanolic ammonia (20%, 0.05 M) is heated in a sealed tube at 120° C. for 16 h. The reaction mixture is concentrated to afford tert-butyl 7-(2-(2-(6-amino-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (B).
[Figure (not displayed)]
To a solution tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(methylamino)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) in acetic anhydride (B, 0.06 M), acetic acid (0.24 M) is added at room temperature and the mixture is heated at 120° C. for 27 h. The reaction mixture is quenched on ice, extracted with ethyl acetate, and the organic layer dried over anhydrous sodium sulfate, filtered, concentrated, and purified by preparative HPLC to afford 7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(N-methylacetamido)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C).
[Figure (not displayed)]
A solution tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) in methanolic ammonia (20%, 0.05 M) is heated in a sealed tube at 120° C. for 16 h. The reaction mixture is concentrated to afford tert-butyl 7-(2-(2-(6-amino-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (B).
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-ethylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) in N,N-dimethylformamide (0.05 M), 1-methylpiperazine (B, 3 equiv.), potassium fluoride (5 equiv.) and 18 crown-6 (1 equiv.) are added and the mixture heated at 90° C. for 3 h. The reaction mixture is cooled, diluted with water, extracted with ethyl acetate, and the combined organic layer dried over anhydrous sodium sulphate, filtered, and concentrated to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(4-methylpiperazin-1-yl)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-ethylthieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
To a solution 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (A, 1 equiv.) and tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride (B, 2 equiv.) in 1,4-dioxane (0.088 M) is added caesium carbonate (0.172 g, 0.530 mmol) and the reaction mixture heated at 90° C. for 3 h. The reaction mixture is diluted with water, extracted with ethyl acetate, and the organic layer dried over anhydrous sodium sulphate, filtered, concentrated, and purified by column chromatography to afford 7-(2-(2-(6-(3-((tert-butoxycarbonyl)(methyl)amino)azetidin-1-yl)-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C1).
To a solution of 7-(2-(2-(6-(3-((tert-butoxycarbonyl)(methyl)amino)azetidin-1-yl)-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C1, 1 equiv.) in dichloromethane (0.045 M), 2,2,2-trifluoroacetic acid (0.14 M) is added at 0° C. and the reaction mixture stirred for 16 h at room temperature. The reaction mixture is concentrated and purified by preparative HPLC to afford 7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(3-(methylamino)azetidin-1-yl)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (C2)
[Figure (not displayed)]
tert-Butyl 7-(2-(2-(6-bromo-5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.), 3-aminopyridine (B, 1.1 equiv.), xantphos (0.2 equiv.), cesium carbonate (3 equiv.), and tris(dibenzylideneacetone)dipalladium(0) (0.2 equiv.) are suspended in 1,4-dioxane (0.047 M) in a screw capped vial equipped with a stir bar. The reaction mixture is sparged with argon for 3 min, then sealed and heated at 100° C. in a heating block for 75 min. The reaction mixture is cooled to room temperature and taken up in a 1:1 N,N dimethylformamide:methanol solution and filtered through a syringe filter. Preparatory HPLC affords tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-6-(pyridin-3-ylamino)-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
To a stirred solution of oxetan-3-amine (B, 1 equiv.), sodium carbonate (3.5 equiv.) in methanol (0.68 M) and 1,5-dichloropentan-3-one (A, 1 equiv.) are added at room temperature and the reaction mixture is heated at 75° C. for 3 h. The reaction mixture is cooled to room temperature, diluted with water, extracted with ethyl acetate, and the ethyl acetate layer is dried over sodium sulfate, concentrated, and purified over a plug of silica gel to afford 1-(oxetan-3-yl)piperidin-4-one (C).
To a solution of 1-(oxetan-3-yl)piperidin-4-one (C, 0.8 g, 5.16 mmol) in dichloromethane (0.5 M) are added ethylamine (2 M in tetrahydrofuran, 1.3 equiv.) and acetic acid (10 M) at room temperature. The reaction mixture is stirred for 60 min and sodium triacetoxyborohydride (1.3 equiv.) is added at 0° C. and stirred for 16 h at room temperature. The reaction is quenched with 10% aqueous sodium hydroxide solution, extracted with methanol in dichloromethane (5%), and the organic layer washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated to afford N-ethyl-1-(oxetan-3-yl)piperidin-4-amine (D).
To a solution of tert-butyl 7-(5-chloro-2-(3-(5-cyano-6-fluoro-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (E, 1 equiv.) in acetonitrile (0.1 M), are added N-ethyl-1-(oxetan-3-yl)piperidin-4-amine (D, 2 equiv.) and N,N-diisopropylethylamine (3 equiv.) at room temperature and the reaction mixture is stirred for 30 h at 100° C. The reaction is cool to room temperature, quenched with water, extracted with ethyl acetate, and the organic layer washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated and purified by Combi flash to afford tert-butyl 7-(5-chloro-2-(3-(5-cyano-6-(ethyl(1-(oxetan-3-yl)piperidin-4-yl)amino)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (F).
[Figure (not displayed)]
To a solution of tert-butyl (2-(difluoromethyl)pyridin-4-yl)(methyl)carbamate (A, 1 equiv.) and acetic acid (10 equiv.) in methanol (0.029 M), 5% rhodium on carbon (0.5 equiv.) is added at room temperature and the mixture heated at 80° C. under 80 psi for 15 hr. The reaction mixture is filtered and concentrated to afford tert-butyl (2-(difluoromethyl)piperidin-4-yl)(methyl)carbamate (B).
To a solution of tert-butyl (2-(difluoromethyl)piperidin-4-yl)(methyl)carbamate (B, 1 equiv.) in THE (0.19 M) are added formaldehyde (37% solution in water, 10 equiv.), acetic acid (9 equiv.) and molecular sieves (˜3× by weight). The mixture is stirred for 30 min at room temperature, sodium triacetoxyboranuide (361 mg, 1.7 mmol) is added and the mixture stirred for 30 min. The reaction mixture is diluted with methanol and the residue passed through a strata ion exchange column, eluting with water three times, then acetonitrile three times, then methanol three times. tert-Butyl (2-(difluoromethyl)-1-methylpiperidin-4-yl)(methyl)carbamate (C) is eluted by washing the column with a solution of dichloromethane, methanol, and ammonium hydroxide (50:40:10).
tert-Butyl (2-(difluoromethyl)-1-methylpiperidin-4-yl)(methyl)carbamate (C, 1 equiv.) in trifluoroacetic acid (0.006 M) is stirred at room temperature for 30 min and the reaction mixture is concentrated to afford 2-(difluoromethyl)-N,1-dimethylpiperidin-4-amine (D).
A mixture of 7-(5-chloro-2-(2-(5-cyano-8-fluoro-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (E, 1 equiv.), 2-(difluoromethyl)-N,1-dimethylpiperidin-4-amine (D, 5 equiv.) and NMP (0.037 M) in DIPEA (7 equiv.) is stirred at room temperature for 30 min. The reaction mixture is filtered and purified by HPLC to afford 7-(5-chloro-2-(2-(5-cyano-8-((2-(difluoromethyl)-1-methylpiperidin-4-yl)(methyl)amino)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (F).
[Figure (not displayed)]
To a dichloromethane (40 mL) solution of tert-butyl 7-(5-chloro-2-(3-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) is added trifluoroacetic acid (0.25 M) at 0° C. and stirred for 17 h at room temperature. The mixture is concentrated in vacuo, aqueous sodium bicarbonate solution added, and washed with diethyl ether. The water layer is acidified with 3 N hydrogen chloride solution and stirred for 15 min. Filtration affords 7-(5-chloro-2-(3-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (B).
To a 7-(5-chloro-2-(3-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (B, 1160 mg, 2.12 mmol) solution in dichloromethane (0.11 M) and methanol (0.42 M) is added trimethylsilyldiazomethane (4 equiv.) at 0° C. Upon stirring for 10 min at 0° C., the reaction is quenched with acetic acid (3.5 M), concentrated and purified by silica gel column chromatography to afford methyl 7-(5-chloro-2-(3-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C).
To a methyl 7-(5-chloro-2-(3-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C, 433 mg, 0.770 mmol) in N-methyl-2-pyrrolidone (0.21 M) is added 1-(2-(trifluoromethoxy)ethyl)piperazine dihydrochloride (D, 1.5 equiv.) at room temperature and the mixture stirred for 2 h at 50° C. followed by 17 h at room temperature. The mixture is diluted with methanol, filtered, and the filtrate purified by preparative HPLC to give methyl 7-(5-chloro-2-(3-(5-cyano-2-methyl-4-oxo-6-(4-(2-(trifluoromethoxy)ethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylate (E).
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) and potassium trifluoro(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)borate (B, 1.4 equiv.) in a mixture of toluene and water (2:1, 0.7 M) is added cesium carbonate (2 equiv.) and the reaction mixture degassed with argon for 15 min. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.1 equiv.) is added and heated at 100° C. for 16 h. The reaction mass is filtered through Celite, washed with ethyl acetate, and the filtrate dried over anhydrous sodium sulfate, concentrated, and purified by Combiflash to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-6-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)pyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C).
To a stirred solution of tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-6-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)pyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C, 1 equiv.) in a mixture of acetonitrile and water (3:1, 0.018 M), selectfluor-II (2 equiv.) is added at 0° C. and the mixture stirred at room temperature for 48 h. The reaction mixture is partitioned between water and ethyl acetate and the organic layer dried over sodium sulfate and concentrated to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(2-hydroxyethyl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (D).
To a solution of tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(2-hydroxyethyl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (D, 1 equiv.) in dichloromethane (0.4 M), diethylaminosulfur trifluoride (1.5 equiv.) is added at 0° C. and the mixture stirred at room temperature for 3 h. The reaction mass is quenched with 10% aqueous sodium hydroxide solution at 0° C., extracted with dichloromethane, and the organic layer dried over anhydrous sodium sulfate and concentrated to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(2-fluoroethyl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (E).
[Figure (not displayed)]
[Figure (not displayed)]
tert-Butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.), PdCl2(PPh3)2 (0.18 equiv.), and (E)-4,4,5,5-tetramethyl-2-(3-((tetrahydro-2H-pyran-2-yl)oxy)prop-1-en-1-yl)-1,3,2-dioxaborolane (B, 1.6 equiv.) are suspended in 1,4-dioxane (0.054 M) in an oven dried microwave vial equipped with a stir bar. Aqueous potassium carbonate (2.0 M, 4 equiv.) is added, and the sealed vial is sparged with argon for 5 min and heated at 100° C. in a microwave reactor for 4 h. The reaction mixture is diluted with saturated aqueous sodium bicarbonate and ethyl acetate and the aqueous phase extracted with ethyl acetate three times. The combined organic material is washed with brine, dried over magnesium sulfate, filtered, and purified via silica gel chromatography to afford tert-butyl (E)-7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-6-(3-((tetrahydro-2H-pyran-2-yl)oxy)prop-1-en-1-yl)pyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C).
tert-Butyl (E)-7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-6-(3-((tetrahydro-2H-pyran-2-yl)oxy)prop-1-en-1-yl)pyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (C, 1 equiv.) is suspended in methanol (0.05 M) and tetrahydrofuran (0.05 M) and water (0.05 M) in a screw capped vial equipped with a stir bar and the reaction mixture stirred at room temperature while p-toluenesulfonic acid (0.35 equiv.) is added in 1 portion. After 30 min the temperature is raised to 55° C. and stirred an additional 1 h. Water (0.1 M) is added and, after 1 h, the temperature raised to 80° C. and heated at this temperature for 8 h. The reaction mixture is cooled to room temperature and volatile solvent is then removed in vacuo. The reaction mixture is diluted with saturated aqueous sodium bicarbonate and ethyl acetate, the layers separated, and the aqueous phase extracted with ethyl acetate three times. The combined organic material is washed with brine, dried over magnesium sulfate, and the solids filtered and concentrated to afford tert-butyl (E)-7-(5-chloro-2-(2-(5-cyano-6-(3-hydroxyprop-1-en-1-yl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (D).
tert-Butyl (E)-7-(5-chloro-2-(2-(5-cyano-6-(3-hydroxyprop-1-en-1-yl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (D, 1 equiv.) is dissolved in dichloromethane (0.086 M) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at 0° C. while N,N-diisopropylethylamine (6 equiv.) is added slowly. Methanesulfonyl chloride (2.6 equiv.) is then added dropwise at which time the ice bath is removed. After 30 min the reaction mixture is diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered and the solvent removed in vacuo, affording tert-butyl (E)-7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(3-((methylsulfonyl)oxy)prop-1-en-1-yl)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (E).
tert-Butyl (E)-7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(3-((methylsulfonyl)oxy)prop-1-en-1-yl)-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (E, 54.5 mg, 0.07 mmol) is dissolved in 1,2-dichloroethane (0.05 M) in a screw capped vial equipped with a stir bar and the reaction mixture stirred at 10° C. while 4,4-difluoropiperidine (F, 3.3 equiv.) is added dropwise. N,N-Diisopropylethylamine (6.6 equiv.) is added dropwise and after 5 min the reaction mixture is warmed to room temperature. After 15 min the temperature is raised to 45° C. and stirring continued for 3 h. The reaction mixture is cooled to room temperature and the solvent is then removed in vacuo. The residue is taken up in DMF and filtered through a syringe filter. Preparatory HPLC afforded the desired product, which is isolated by passing HPLC fractions through a strata ion exchange column, then washing with a solution of dichloromethane, methanol, and ammonium hydroxide. The solvent is to afford tert-butyl (E)-7-(5-chloro-2-(2-(5-cyano-6-(3-(4,4-difluoropiperidin-1-yl)prop-1-en-1-yl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (G).
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.), tributyl(methoxymethyl)stannane (B, 1.5 equiv.) in 1-methyl-2-pyrrolidinone (0.1 M) is degassed using argon for 10 min and tetrakis(triphenylphosphine)palladium (0) (0.055 g, 0.048 mmol) is added at room temperature and heated at 130° C. for 10 h. The reaction mixture is cooled to room temperature, diluted with water and, extracted with ethyl acetate, and the ethyl acetate layer dried over sodium sulfate, concentrated, and purified by preparative HPLC to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(methoxymethyl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-(2-(6-chloro-5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (A, 1 equiv.) and (2-fluorophenyl)boronic acid (B, 1.5 equiv.) in 1,4-dioxane is added 2 M aqueous potassium carbonate solution (3 equiv.) and reaction mixture degassed with argon gas for 10 min. [1,1′-Bis(diphenylphosphino)ferrocene] dichlopalladium(II)dichlomethane complex (0.05 equiv.) is added and degassed with argon gas for 5 min and the reaction mixture is heated at 90° C. for 3 h. The reaction mixture is diluted with water, extracted with ethyl acetate, and the organic layer dried over anhydrous sodium sulphate, filtered, concentrated, and purified by column chromatography to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-(2-fluorophenyl)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (C).
[Figure (not displayed)]
To a solution of 7-(5-chloro-2-(3-(5-cyano-6-((1-(2,2-difluoropropyl)piperidin-4-yl)(methyl)amino)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (A, 1 equiv.) and oxetane-3-sulfonamide (B, 2.5 equiv.) in dichloromethane (0.07 M) is added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2 equiv.) and 4-(dimethylamino)pyridine (2.5 equiv.) at 0° C. and stirred at room temperature for 12 h. The reaction mixture is diluted with water, extracted with dichloromethane, and the organic layer dried over anhydrous sodium sulphate, filtered, concentrated, and purified by preparative HPLC to afford 7-(5-chloro-2-(3-(5-cyano-6-((1-(2,2-difluoropropyl)piperidin-4-yl)(methyl)amino)-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)phenyl)-N-(oxetan-3-ylsulfonyl)thieno[3,2-b]pyridine-3-carboxamide (C).
[Figure (not displayed)]
To a stirred solution of 5-bromo-3-(3-(2-bromo-4-chlorophenyl)prop-2-yn-1-yl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (6, 0.6 g, 1.28 mmol) in N,N-dimethylformamide, copper(I) cyanide (0.138 g, 1.53 mmol) is added and the reaction mixture is heated and stirred at 90° C. for 16 h. After completion, the reaction mass is diluted with ethyl acetate and washed with cold water. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude compound is purified by Combi-flash using 50% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 3-(3-(2-bromo-4-chlorophenyl)prop-2-yn-1-yl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (7).
A stirred solution of 3-(3-(2-bromo-4-chlorophenyl)prop-2-yn-1-yl)-2-methyl-4-oxo-3,4-dihydropyrido[3,4-d]pyrimidine-5-carbonitrile (7, 0.1 g, 0.24 mmol), 4-boronophthalic acid (8, 0.075 g, 0.36 mmol) and potassium carbonate (0.099 g, 0.72 mmol) in a mixture of dioxane, N,N-dimethylformamide and water (1.2 mL, 0.6 mL, 0.2 mL respectively) is degassed with argon for 25 min. Dichlorobis(triphenylphosphine)palladium(II) is added and the reaction mixture is heated and stirred at 90° C. for 2 h. After completion, volatiles are removed under reduced pressure to obtain the residue. This residue is diluted with water, acidified with 1 N aqueous hydrochloric acid and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the compound. This compound is purified by preparative HPLC to afford 5′-chloro-2′-(3-(5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)prop-1-yn-1-yl)-[1,1′-biphenyl]-3,4-dicarboxylic acid (9).
[Figure (not displayed)]
To a solution of methyl 2-amino-5′-chloro-2′-(2-(5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-[1,1′-biphenyl]-3-carboxylate (3, 1.5 g, 3.06 mmol) in acetonitrile (40 mL), tert-butyl nitrite (0.50 g, 4.8 mmol) is added at room temperature. Suspension of copper(I) iodide (0.93 g, 3.06 mmol) in acetonitrile (10 mL) is added drop wise over a period of 10 min at room temperature. The reaction mixture is stirred at 60° C. for 4 h. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with aqueous sodium thiosulphate, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford crude. The crude is purified by flash column chromatography using 0-40% ethyl acetate in hexane to afford methyl 5′-chloro-2′-(2-(5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-2-iodo-[1,1′-biphenyl]-3-carboxylate (4).
A solution of methyl 5′-chloro-2′-(2-(5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-2-iodo-[1,1′-biphenyl]-3-carboxylate (4, 0.57 g, 0.95 mmol) in dioxane (20 mL) is degassed for 10 min using argon. Tributyl(ethynyl)stannane (5, 0.6 g, 1.86 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.076 g, 0.066 mmol) are added and the reaction mixture is stirred at 90° C. for 16 h. After completion, reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate filtered and concentrated to dryness under reduced pressure. The crude is purified by flash column chromatography using 0-40% ethyl acetate in hexanes to afford methyl 5′-chloro-2′-(2-(5-cyano-2-methyl-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-2-ethynyl-[1,1′-biphenyl]-3-carboxylate (6).
Compounds made using one or more of the general methods described above are shown in Table 1. Where provided, characterization data is to the right of the compounds.
TABLE 1
7-Aza-Thienylpyridine and Derivative Compounds
Com-
poundCharacterization
34[Figure (not displayed)]
MS (ESI) m/z 447.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.23 (s, 1H), 9.07 (s, 1H), 8.20 (s, 1H), 7.88 (s, 1H), 7.84 (d, J = 7.68, 1H), 7.61 (d, J = 7.72, 1H), 7.45- 7.39 (m, 2H), 7.33 (d, J = 2.5 Hz, 1H), 7.21 (d, J = 8.84Hz, 1H), 4.35 (s, 4H)
35[Figure (not displayed)]
MS (ESI) m/z 462.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 9.03 (s, 1H), 8.63 (d, J = 4.8 Hz, 1H), 7.94 (d, J = 0.8 Hz, 1H), 7.59 (dd, J = 4.8 Hz, 1H), 7.48 (dd, J = 4.4 Hz, 1H), 7.409 (d, J = 2.8 Hz, 1H), 7.249 (d, J = 8.8 Hz, 1H), 4.386 (s, 4H), 2.22 (s, 3H)
36[Figure (not displayed)]
MS (ESI) m/z 486.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 7.87 (d, J = 7.68 Hz, 1H), 7.83 (s, 1H), 7.49 (d, J = 7.68 Hz, 1H), 7.43-7.38 (m, 2H), 7.27 (d, J = 2.6 Hz, 1H), 7.20 (d, J = 8.88 Hz, 1H), 4.39-4.35 (dd, J = 12.52 Hz, 4H), 2.29 (s, 3H)
38[Figure (not displayed)]
MS (ESI) m/z 529.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.13 (s, 1H), 7.87-7.85 (m, 2H), 7.56 (d, J = 7.76 Hz, 1H), 7.42-7.38 (m, 2H), 7.29 (d, J = 2.64 Hz, 1H), 7.21 (d, J = 8.92 Hz, 1H), 4.37 (m, 4H), 2.24 (s, 3H)
39[Figure (not displayed)]
MS (ESI) m/z 554.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 9.19 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 7.61 (dd, J = 2.64, 8.88, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 2.68 Hz, 1H), 7.37 (d, J = 8.96 Hz, 1H), 6.72-6.46 (t, J = 51.6 Hz, 1H), 4.41 (d, J = 4.64 Hz, 2H), 4.36 (d, J = 4.52 Hz, 2H)
44[Figure (not displayed)]
MS (ESI) m/z 457.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 9.18 (s, 1H), 9.04 (s, 1H), 7.9-7.83 (m, 1H), 7.76 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.52-7.44 (m, 3H), 7.36 (d, J = 2.2 Hz, 1H), 6.42-6.35 ( m, 1H), 6.22 (d, J = 16.04 Hz, 1H), 4.82 (d, J = 4.8 Hz, 2H), 2.58 (s, 3H)
45[Figure (not displayed)]
MS (ESI) m/z 510.44 [M − 1]−; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.98 (s, 1H), 8.96 (d, J = 4.56 Hz, 1H), 8.17 (d, J = 7.52 Hz, 1H), 7.64 (s, 1H), 7.56 (dd, J = 8.92 Hz, 1H), 7.44 (d, J = 4.56 Hz, 1H), 7.30 (d, J = 2.56 Hz, 1H), 7.26 (d, J = 8.96 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 4.33-4.29 (m, 2H), 4.24-4.17 (m, 1H), 4.12-4.06 (m, 1H), 1.84 (s, 3H)
48[Figure (not displayed)]
MS (ESI) m/z 475.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.16 (s, 1H), 9.18 (s, 1H), 9.05 (s, 1H), 7.36 (dd, J = 8.8 Hz, 1H), 7.28 (t, 2H), 7.24-7.18 (m, 5 H), 4.57 (t, 2H), 4.33 (t, 2H), 2.87 (t, 2H) 2.57 (t, 2H)
49[Figure (not displayed)]
MS (ESI) m/z 553.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) d 12.17 (bs, 1H), 8.84 (d, J = 4.76 Hz, 1H), 8.41 (s, 1H), 7.72 (dd, J = 10.68 Hz, 7.56 Hz, 1H),7.60 (dd, J = 8.08, 2.60 Hz, 1H), 7.48 (d, J = 4.76 Hz, 1H), 7.41 (d, J = 2.52 Hz, 1H), 7.36 (d, J = 8.08 Hz, 1H), 4.39 (t, J = 4.64 Hz, 2H). 4.23 (t, J = 4.68 Hz, 2H), 1.77 (s, 3H)
50[Figure (not displayed)]
MS (ESI) m/z 619.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 4.4 Hz, 1H), 8.24 (s, 1H), 8.08 (s, 1H), 7.60 (dd, J = 8.8, 2.6 Hz, 1H), 7.51 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 4.7 Hz, 2H), 4.25 (t, J = 4.7 Hz, 2H), 1.69 (s, 3H)
140[Figure (not displayed)]
MS (ESI) m/z 518.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.029 (d, J = 1.24 Hz, 2H), 8.835 (d, J = 4.76 Hz, 1H), 8.379 (s, 1H), 7.596 (dd, J = 2.6, 8.96 Hz, 1H), 7.48 (d, J = 4.72 Hz, 1H), 7.439 (d, J = 2.52 Hz, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.403 (t, J = 4.68 Hz, 2H), 4.255 (t, J = 6.04 Hz, 2H), 1.787 (s, 3H)
147[Figure (not displayed)]
MS (ESI) m/z 505 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 9.00 (s, 1H), 8.139 (m, J = 8.04 Hz, 2H), 7.44 (m, J = 7.92 Hz, 2H), 7.28 (d, J = 2.76 Hz, 1H), 7.19 (d, J = 8.92 Hz, 1H), 4.35 (s, 4H), 2.22 (s, 3H)
149[Figure (not displayed)]
MS (ESI) m/z 497.38 [M − 1]−; 1H NMR (400 MHz, DMSO-d6) δ 9.158 (s, 1H), 9.033 (s, 1H), 8.291 (s, 1H), 8.117 (d, J = 8.2 Hz, 1H), 7.63 (d, J = 8.28 Hz, 1H), 7.6 (dd, J = 1.96, 8.12 Hz, 1H), 7.53 (d, J = 1.96 Hz, 1H), 7.49 (dd, J = 2.2, 8.4 Hz, 1H), 5.05 (s, 2H), 2.35 (s, 3H)
150FA[Figure (not displayed)]
MS (ESI) m/z 497 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 9.03 (s, 1H), 7.68- 7.63 (m, 2H), 7.47-7.38 (m, 3H), 7.23 (d, J = 2.6 Hz, 1H), 7.18 (d, J = 8.88 Hz, 1H), 4.37- 4.22 (m, 4H), 2.25 (s, 3H)
150FB[Figure (not displayed)]
MS (ESI) m/z 539 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 9.03 (s, 1H), 7.25 (d, J = 2.6 Hz, 1H), 7.19 (d, J = 8.8 Hz, 1H),7.63- 7.67 (m, 2H), 7.50 (d, J = 6.5 Hz, 1H), 7.41- 7.44 (m, 1H), 7.41 (dd, J = 2.8 Hz, J'= 2.6 Hz, 1H), 4.36 (s, 4H), 4.41-4.48 (m, 1H), 2.24 (s, 3H), 1.19 (d, J = 6.2 Hz, 6H)
150FC[Figure (not displayed)]
MS (ESI) m/z 472 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.9 (s, 1H), 8.62 (d, J = 5.2 Hz, 1H), 7.91 (d, J = 5.16 Hz, 1H), 7.63-7.72 (m, 2H), 7.40-7.44 (m, 3H), 7.24 (d, J = 2.64 Hz, 1H), 7.19 (d, J = 8.84, 1H), 4.33-4.37 (m, 4H), 2.28 (s, 3H)
151[Figure (not displayed)]
MS (ESI) m/z 696.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.69 (bs, 1H), 68.92 (d, J = 4.4 Hz, 1H), 6 8.34 (s, 1H), 6 8.09 (s, 1H), 6 7.63-7.57 (m, 2H), 67.45 (d, J = 2.0 Hz, 1H), 6 7.36 (d, J = 8.8 Hz, 1H), 6 4.42 (t, 4.8 Hz, 2H), 6 4.24 (t, J = 4.8, 2H), 6 3.56 (s, 3H), 6 1.65 (s, 3H)
152[Figure (not displayed)]
MS (ESI) m/z 579.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.96 (b, 1H), 8.74(d, J = 4.72 Hz, 1H), 8.62 (s, 1H), 8.13 (d, J = 9.76 Hz, 1H), 7.76 (d, J = 9.76 Hz, 1H), 7.68 (t, J = 2.04 Hz, 1H), 7.53 (d, J = 4.72 Hz, 1H), 7.3 (t, J = 53.68 Hz, 1H), 4.88 (s, 2H), 2.22(s, 3H)
155[Figure (not displayed)]
MS (ESI) m/z 485.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.89 (bs, 1H), 9.17 (s, 1H), 9.00 (s, 1H), 7.88 (m, 1H), 7.46-7.36 (m, 3H), 7.16-7.12 (m, 2H), 4.32 (bs, 4H), 3.67 (s, 1H), 1.98 (s, 3H)
157[Figure (not displayed)]
MS (ESI) m/z 511.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.87 (s, 1H), 9.23 (s, 1H), 7.88-7.86 (dd, J = 1.28, J = 6.8 Hz, 1H), 7.80 (d, J = 1.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.45-7.17 (m, 5H), 4.36 (s, 4H), 2.19 (s, 3H)
183[Figure (not displayed)]
MS (ESI) m/z 690.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 4.89 (dt, J = 47.1, 4.7 Hz, 2H), 4.44-4.33 (m, 3H), 4.23 (t, J = 5.1 Hz, 2H), 3.93 (hept, J = 6.8 Hz, 1H), 3.79-3.52 (m, 7H), 1.87 (s, 3H), 1.25 (d, J = 6.8 Hz, 6H)
184[Figure (not displayed)]
MS (ESI) m/z 561.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 9.08 (s, 1H), 8.32 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.39-7.16 (m, 5H), 4.34 (d, J = 3.6 Hz, 6H), 3.25-3.18 (m, 3H), 2.89 (s, 2H), 1.42 (d, J = 15 Hz, 4H), 1.27- 1.18 (m, 2H)
260[Figure (not displayed)]
MS (ESI) m/z 636.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.82 (d, J = 4.9 Hz, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.50- 3.41 (m, 1H), 2.24-1.94 (m, 8H), 1.83 (s, 3H)
284[Figure (not displayed)]
MS (ESI) m/z 636.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 4.25 (t, J = 4.9 Hz, 2H), 3.94- 3.82 (m, 1H), 2.23-1.94 (m, 6H), 1.86 (td, J = 12.7, 12.1, 4.2 Hz, 2H), 1.80 (s, 3H)
338[Figure (not displayed)]
MS (ESI) m/z 560.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) d/ppm = 8.89 (s, 1H), 8.49 (s, 1H), 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.43- 7.41 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.43 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 3.19 (q, J = 7.5 Hz, 2H), 2.69 (s, 3H), 1.93 (s, 3H), 1.27 (t, J = 7.5 Hz, 3H)
339[Figure (not displayed)]
MS (ESI) m/z 572.1; 1H-NMR (400 MHz, d6- DMSO) d/ppm = 8.77 (s, 1H), 8.59 (s, 1H), 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.41 (s, 1H), 7.36 (d, J = 8.9 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.0 Hz, 2H), 3.21-3.11 (m, 1H), 2.68 (s, 3H), 1.92 (s, 3H), 1.33-1.26 (m, 1H), 1.21-1.15 (m, 1H)
340[Figure (not displayed)]
MS (ESI) m/z 600.2 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) d/ppm = 9.11 (s, 1H), 8.63 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46- 7.44 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.44 (t, J = 4.9 Hz, 2H), 4.30 (t, J = 4.9 Hz, 2H), 2.70 (s, 3H), 2.05 (s, 3H)
365[Figure (not displayed)]
MS (ESI) m/z 603.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.58 (s, 1H), 8.96 (s, 1H), 8.34 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.1 Hz, 2H), 3.69-3.61 (m, 2H), 3.58-3.50 (m, 2H), 2.93 (s, 3H), 2.92 (s, 3H), 2.72 (s, 3H), 1.92 (s, 3H)
372[Figure (not displayed)]
MS (ESI) m/z 582.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.59 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.52 (t, J = 53.5 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.40 (s, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.0 Hz, 2H), 2.66 (s, 3H), 1.90 (s, 3H)
384[Figure (not displayed)]
MS (ESI) m/z 552.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.62 (s, 1H), 7.80-7.73 (m, 1H), 7.72- 7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.86 (s, 2H), 2.67-2.61 (m, 1H), 2.09 (s, 3H), 1.29- 1.15 (m, 4H)
385[Figure (not displayed)]
MS (ESI) m/z 649.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.84 (s, 1H), 8.56 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.40 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.1 Hz, 2H), 4.25 (t, J = 5.1 Hz, 2H), 3.57 (s, 3H), 2.68 (s, 3H), 2.61 (tt, J = 7.6, 4.9 Hz, 1H), 1.87 (s, 3H), 1.31-1.13 (m, 4H)
400[Figure (not displayed)]
MS (ESI) m/z 644.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.44-7.38 (m, 2H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.87-3.78 (m, 2H), 3.26 (td, J = 11.7, 2.1 Hz, 2H), 2.96 (d, J = 7.1 Hz, 2H), 2.73 (s, 3H), 2.69 (s, 3H), 2.15-2.02 (m, 1H), 1.92 (s, 3H), 1.56-1.47 (m, 2H), 1.33 (qd, J = 12.0, 4.4 Hz, 2H)
418[Figure (not displayed)]
MS (ESI) m/z 572.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.42 (s, 1H), 7.59 (dd, J = 8.8, 2.6 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 2.70 (s, 3H), 2.65-2.56 (m, 1H), 1.86 (s, 3H), 1.27-1.14 (m, 4H)
419[Figure (not displayed)]
MS (ESI) m/z 546.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.38 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 2.6 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 2.79 (s, 3H), 2.71 (s, 3H), 1.88 (s, 3H)
420[Figure (not displayed)]
MS (ESI) m/z 588.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.46 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.5 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 5.1 Hz, 2H), 4.24 (t, J = 5.1 Hz, 2H), 2.71 (s, 3H), 1.86 (s, 3H), 1.58 (s, 9H)
432[Figure (not displayed)]
MS (ESI) m/z 574.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.42 (s, 1H), 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 4.9 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.64 (hept, J = 6.8 Hz, 1H), 2.70 (s, 3H), 1.87 (s, 3H), 1.33 (d, J = 6.7 Hz, 6H)
435[Figure (not displayed)]
MS (ESI) m/z 587.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.52-8.47 (m, 2H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.40-7.35 (m, 2H), 7.31 (d, J = 9.0 Hz, 1H), 4.37-4.29 (m, 6H), 4.16 (t, J = 5.1 Hz, 3H), 2.68 (s, 3H), 2.40- 2.28 (m, 2H), 1.79 (s, 3H)
441[Figure (not displayed)]
MS (ESI) m/z 655.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 2.7 Hz, 1H), 8.48 (s, 1H), 8.06 (dd, J = 9.1, 2.8 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.34 (m, 3H), 4.46 (t, J = 5.0 Hz, 2H), 4.30 (t, J = 5.1 Hz, 2H), 2.79 (s, 3H), 2.72 (s, 3H), 2.35 (s, 3H), 2.00 (s, 3H)
448[Figure (not displayed)]
MS (ESI) m/z 630.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.48 (s, 1H), 7.61 (dd, J = 9.0, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41-7.37 (m, 2H), 4.43 (t, J = 5.1 Hz, 2H), 4.33 (d, J = 14.1 Hz, 2H), 4.24 (t, J = 5.1 Hz, 2H), 3.60 (d, J = 11.9 Hz, 2H), 3.33-3.19 (m, 2H), 2.91 (d, J = 3.1 Hz, 3H), 2.66 (s, 3H), 1.89 (s, 3H)
450[Figure (not displayed)]
MS (ESI) m/z 638.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (dd, J = 8.4, 2.2 Hz, 1H), 7.63 (d, J = 2.1 Hz, 1H), 7.46 (s, 1H), 4.81 (s, 2H), 4.35 (d, J = 14.1 Hz, 2H), 3.62 (d, J = 12.0 Hz, 2H), 3.48-3.23 (m, 6H), 2.92 (d, J = 3.5 Hz, 3H), 2.74 (s, 3H), 2.66 (s, 3H), 2.17 (s, 3H)
459[Figure (not displayed)]
MS (ESI) m/z 560.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.72- 7.63 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.85 (s, 2H), 2.78 (d, J = 10.6 Hz, 6H), 2.15 (s, 3H)
474[Figure (not displayed)]
LCMS: 640.2 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.99-7.89 (m, 2H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48-7.31 (m, 5H), 4.45 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.1 Hz, 2H), 2.79 (s, 3H), 2.71 (s, 3H), 1.97 (s, 3H)
475[Figure (not displayed)]
LCMS: 640.2 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.79-7.68 (m, 2H), 7.66-7.57 (m, 2H), 7.45-7.34 (m, 4H), 4.45 (t, J = 5.1 Hz, 2H), 4.29 (t, J = 5.0 Hz, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 1.99 (s, 3H)
476[Figure (not displayed)]
LCMS: 640.2 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 7.72 (td, J = 7.7, 1.9 Hz, 1H), 7.67-7.57 (m, 2H), 7.47-7.34 (m, 5H), 4.44 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.0 Hz, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 1.96 (s, 3H)
477[Figure (not displayed)]
LCMS: 636.7 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.52 (s, 1H), 7.81-7.75 (m, 2H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46-7.32 (m, 5H), 4.45 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.1 Hz, 2H), 2.78 (d, J = 0.7 Hz, 3H), 2.71 (s, 3H), 2.42 (s, 3H), 1.94 (s, 3H)
478[Figure (not displayed)]
LCMS: 636.8 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.70-7.63 (m, 2H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48-7.33 (m, 5H), 4.45 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.0 Hz, 2H), 2.79 (s, 3H), 2.71 (s, 3H), 2.43 (s, 3H), 1.94 (s, 3H)
479[Figure (not displayed)]
LCMS: 636.8 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.52 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (dq, J = 3.9, 2.0 Hz, 4H), 7.42- 7.31 (m, 3H), 4.44 (t, J = 5.0 Hz, 2H), 4.28 (d, J = 4.9 Hz, 2H), 2.77 (s, 3H), 2.71 (s, 3H), 2.18 (s, 3H), 1.90 (s, 3H)
480[Figure (not displayed)]
LCMS: 656.4 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.92 (d, J = 2.1 Hz, 1H), 7.91 (d, J = 2.1 Hz, 1H), 7.68-7.63 (m, 2H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45-7.36 (m, 3H), 4.45 (t, J = 5.0 Hz, 2H), 4.29 (t, J = 4.9 Hz, 2H), 2.79 (s, 3H), 2.70 (s, 3H), 1.97 (s, 3H)
481[Figure (not displayed)]
LCMS: 656.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 7.94 (td, J = 1.9, 0.6 Hz, 1H), 7.85 (dt, J = 7.1, 1.7 Hz, 1H), 7.67- 7.57 (m, 3H), 7.45-7.36 (m, 3H), 4.46 (t, J = 5.1 Hz, 2H), 4.29 (t, J = 5.0 Hz, 2H), 2.79 (s, 3H), 2.72 (s, 3H), 1.99 (s, 3H)
482[Figure (not displayed)]
LCMS: 656.7 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.70-7.63 (m, 2H), 7.62-7.52 (m, 3H), 7.46-7.41 (m, 2H), 7.38 (d, J = 9.0 Hz, 1H), 4.44 (t, J = 5.0 Hz, 2H), 4.28 (s, 2H), 2.79 (s, 3H), 2.71 (s, 3H), 1.94 (s, 3H)
491[Figure (not displayed)]
MS (ESI) m/z 574.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.59 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.50-7.41 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 4.12-4.00 N (m, 1H), 2.68 (s, 3H), 1.94 (s, 3H), 1.26 (d, J = 6.8 Hz, 6H)
492[Figure (not displayed)]
MS (ESI) m/z 560.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.42-7.35 (m, 4H), 4.43 (t, J = 5.1 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 2.72 (d, J = 3.2 Hz, 6H), 2.70 (s, 3H), 1.96 (s, 3H)
597[Figure (not displayed)]
MS (ESI) m/z 532.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.0 (d, J = 5.6 Hz, 1H), 8.38 (s, 1H), 7.59 (dd, J = 8.8, 2.5 Hz, 1H), 7.41 (d, J = 2.1 Hz, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.4 (t, J = 4.2 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 2.7 (s, 3H), 1.85 (s, 3H)
600[Figure (not displayed)]
MS (ESI) m/z 609.11 [M + 1; 1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 9.01 (d, J = 5.44, 1H), 8.51 (s, 1H), 7.62-7.56 (m, 1H), 7.49-7.31 (m, 3H), 4.41 (s, 2H), 4.26 (s, 2H), 3.58 (s, 3H), 2.69 (s, 3H), 1.91 (s, 3H)
601[Figure (not displayed)]
MS (ESI) m/z 526.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 9.08 (s, 1H), 8.61 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.69-7.66 (m, 2H), 7.46 (s, 1H), 4.87 (s, 2H), 2.61 (s, 3H), 2.16 (s, 3H)
602[Figure (not displayed)]
MS (ESI) m/z 598.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.40 (s, 1H), 7.85 (t, J = 72.0 Hz, 1H), 7.59 (d, J = 8.92 Hz, 1H), 7.42 (bs, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 5.12 Hz, 2H), 4.25 (t, J = 4.44 Hz, 2H), 2.71 (s, 3H), 1.82 (s, 3H)
603[Figure (not displayed)]
MS (ESI) m/z 642.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.85 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.53 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz 1H), 7.39 (d, J = 9.0 Hz 1H), 4.55- 4.38 (m, 3H), 4.30-4.15 (m, 2H), 3.66-3.44 (m, 4H), 3.27-3.12 (m, 1H), 3.05-2.83 (m, 4H), 2.64 (s, 3H), 1.85 (s, 3H), 1.44-1.22 (m, 2H)
604[Figure (not displayed)]
MS (ESI) m/z 598.18 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.66 (s ,1H), 8.54 (s, 1H), 7.82 (t, J = 71.4 Hz, 1H), 7.60 (dd, J = 2.52, 8.84 Hz, 1H), 7.42 (d, J = 2.5 Hz, 1H), 7.40 (s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.42 (t, J = 5.46 Hz, 2H), 4.29 (t, J = 5.46 Hz, 2H), 2.71 (s, 3H), 2.01 (s, 3H)
624[Figure (not displayed)]
MS (ESI) m/z 512.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 9.06 (s, 1H), 8.74 (d, J = 4.76 Hz, 1H), 8.61 (s, 1H), 7.76 (d, J = 8.96, 1H), 7.70-7.65 (m, 2H), 7.54 (d, J = 4.76, 1H), 4.87 (s, 2H), 2.13 (s, 3H)
656[Figure (not displayed)]
MS (ESI) m/z 636.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.83 (s, OH), 8.78 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.69 (dd, J = 8.3, 2.2 Hz, 1H), 7.66 (d, J = 2.1 Hz, 1H), 7.54 (d, J = 4.8 Hz, 1H), 4.91- 4.76 (m, 2H), 4.57 (d, J = 14.5 Hz, 1H), 3.73- 3.12 (m, 4H), 3.08-2.87 (m, 4H), 2.71 (s, 3H), 2.10 (s, 3H), 1.51 (s, 1H), 1.41-1.29 (m, 1H)
673[Figure (not displayed)]
LCMS (ESI) m/z 546.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.44 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.41-7.35 (m, 2H), 7.33 (d, J = 9.0 Hz, 1H), 4.40 (s, 2H), 4.23 (s, 2H), 2.72 (s, 3H), 2.67 (s, 3H), 1.88 (s, 3H)
674[Figure (not displayed)]
LCMS (ESI) m/z 531.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.82 (dd, J = 4.8, 1.0 Hz, 1H), 8.48 (d, J = 2.0 Hz, 1H), 7.64- 7.56 (m, 1H), 7.52-7.40 (m, 2H), 7.36 (dd, J = 9.0, 4.8 Hz, 1H), 4.43 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 4.9 Hz, 2H), 2.76 (s, 3H), 1.85- 1.78 (m, 3H)
707[Figure (not displayed)]
MS (ESI) m/z 616.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.32 (d, J = 14.2 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 3.61 (d, J = 12.0 Hz, 2H), 3.45 (t, J = 13.1 Hz, 2H), 3.32- 3.21 (m, 2H), 2.91 (d, J = 3.5 Hz, 3H), 1.84 (s, 3H)
721[Figure (not displayed)]
MS (ESI) m/z 560.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.73 (bs, 1H), 8.85 (s, 1H), 7.68 (s, 1H), 7.47 (dd, J = 2.64, 8.88 Hz, 1H), 7.28 (d, J = 2.60 Hz, 1H), 7.24 (d, J = 8.88 Hz, 1H), 7.19 (d, J = 8.00 Hz, 1H), 6.98 (d, J = 8.16 Hz, 1H), 4.34 (t, J = 4.60 Hz, 2H), 4.24 (t, J = 4.32 Hz, 2H), 3.93 (s, 3H), 2.79 (s, 3H), 1.86 (s, 3H)
722[Figure (not displayed)]
MS (ESI) m/z 544.96 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 8.84 (s, 1H), 7.92 (s, 1H), 7.49 (dd, J = 2.48 Hz, J = 8.84 Hz, 1H), 7.28-7.24 (m, 3H), 7.13 (d, J = 7.32 Hz, 1H), 4.35 (t, J = 4.56 Hz, 2H), 4.21 (t, J = 4.48 Hz, 2H), 2.79 (s, 3H), 2.67 (s, 3H), 1.76 (s, 3H)
723[Figure (not displayed)]
MS (ESI) m/z 564.90 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.52 (s, 1H), 7.97 (s, 1H), 7.53-7.48 (m, 2H), 7.34 (d, J = 2.4Hz , 1H), 7.28 (d, J = 8.8 Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 4.36 (t, J = 4.44 Hz, 2H), 4.22 (t, J = 4.4 Hz, 2H), 2.81 (s, 3H), 1.79 (s, 3H)
725[Figure (not displayed)]
MS (ESI) m/z 574 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.92 (bs, 1H), 8.35 (s, 1H), 7.96 (s, 1H), 7.49 (dd, J = 8.84, 2.48 Hz, 1H), 7.27- 7.21 (m, 3H), 7.12 (d, J = 7.32 Hz, 1H), 4.33 (t, J = 4.56 Hz, 2H), 4.17 (t, J = 4.44 Hz, 2H) 3.41 (s, 6H), 2.65 (s, 3H), 1.67 ( s, 3H)
726[Figure (not displayed)]
MS (ESI) m/z 560.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.58 (s, 1H), 7.94 (s, 1H), 7.48 (dd, J = 8.88, 2.64 Hz, 1H), 7.28-7.22 (m, 3H), 7.37 (d, J = 7.36 Hz, 1H), 4.34 (s, 2H), 4.20 (s, 2H), 4.09 (s, 3H), 2.67 (s, 3H), 1.80 (s, 3H)
727[Figure (not displayed)]
MS (ESI) m/z 574.98 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 8.96 (s, 1H), 7.93 (s, 1H), 7.48 (dd, J = 8.88, 2.56 Hz, 1H), 7.28-7.24 (m, 3H), 7.12 (d, J = 7.36, 1H), 4.95 (s, 2H), 4.34 (t, J = 4.4 Hz, 2H), 4.20 (t, J = 4.84 Hz, 2H), 3.41 (s, 3H), 2.66 (s, 3H), 1.74 (s, 3H)
728[Figure (not displayed)]
MS (ESI) m/z 595.96 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H) 7.60 (dd, J = 8.88, 2.76 1H), 7.42-7.08 (m, 4H), 4.43 (t, J = 4.68 Hz, 2H), 4.27 (t, J = 4.44 Hz, 2H), 2.79 (s, 3H), 2.70 (s, 3H), 1.91 (s, 3H)
730[Figure (not displayed)]
MS (ESI) m/z 614.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 8.48 (s, 1H), 7.59 (d, J = 8.72 Hz, 1H), 7.42 (d, J = 4.8 Hz, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.44 (bs, 2H), 4.29 (bs, 2H), 2.80 (s, 3H), 2.71 (s, 1H), 1.94 (s, 1H
731[Figure (not displayed)]
MS (ESI) m/z 622.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 8.83 (s, 1H), 8.63 (s, 1H), 7.61 (dd, J = 2.44, 8.84 Hz, 1H), 7.45 (s,1H), 7.39 (d, J = 9.4 Hz, 2H), 4.43 (t, J = 4.48 Hz, 2H), 4.28 (t, J = 4.6 Hz, 2H), 3.56 (s, 3H), 2.75 (s, 3H), 2.69 (s, 3H), 2.01 (s, 3H)
732[Figure (not displayed)]
MS (ESI) m/z 616.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 at high temperature) 6 8.96 (s, 1H), 8.75 (s, 1H), 7.56-7.52 (dd, J = 6.4 Hz, 9.2 Hz, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.36 (s, 1H), 7.27 (bs, 1H), 4.43 (t, J = 5.2 Hz, 2H), 4.28 (t, J = 4.8 Hz, 2H), 2.73 (s, 3H), 2.63 (s, 3H), 2.00 (s, 3H)
733[Figure (not displayed)]
MS (ESI) m/z 599.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.11 (s, 1H), 7.55-7.52 (dd, J = 2.4, 8.8 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.19 (s, 1H), 5.74-5.69 (m, 1H), 4.38 (t, J = 4.4 Hz, 2H), 4.26 (t, J = 4.4 Hz, 2H), 2.79 (s, 3H), 2.57 (s, 3H), 1.79 (s, 3H)
734[Figure (not displayed)]
MS (ESI) m/z 644.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.59 (dd, J = 8.88, 2.44 Hz, 1H), 7.41 (s, 2H), 7.36 (d, J = 8.96, 1H), 4.42 (t, J = 4.52 Hz, 2H), 4.25 (t, J = 4.4 Hz, 2H), 3.79 (t, J = 10.28 Hz, 2H), 3.26 (t, J = 11.36 Hz, 2H), 2.96 (d, J = 6.92 Hz, 2H), 2.73 (s, 3H), 2.69 (s, 3H), 2.09 (bs, 1H), 1.92 (s, 3H), 1.51 (d, J = 11.16 Hz, 2H), 1.39-1.28 (m, 2H)
737[Figure (not displayed)]
MS (ESI) m/z 622.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.51 (bs, 1H), 8.50 (s, 1H), 7.55 (bs, 2H), 7.64-7.7.45 (m, 4H), 7.42-7.36 (m, 3H), 4.44 (bs, 2H), 4.28 (bs, 2H), 2.78 (s, 3H), 2.69 (s, 3H), 1.94 (s, 3H)
742[Figure (not displayed)]
MS (ESI) m/z 586.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6): 6 13.5 (bs, 1H), 8.49 (s, 1H), 7.60-7.57 (dd, J = 2.4, 8.8 Hz, 1H), 7.39-7.35 (m, 3H), 4.42 (t, J = 4.4 Hz, 2H), 4.25 (t, J = 3.6 Hz), 2.68 (s, 3H), 2.66 (s, 3H), 1.90 (s, 3H), 1.18-1.16 (m, 4H)
749[Figure (not displayed)]
MS (ESI) m/z 668.00 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 611.6 (bs, 1H), 8.86 (s, 1H), 8.47 (s, 1H), 7.58-7.55 (m, 1H), 7.51 (d, J = 2.4 Hz, 1H), 7.39 (s, 1H), 7.34 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 4.8 Hz, 2H), 4.27 (t, J = 5.20 Hz, 2H), 2.77 (s, 3H), 2.59 (s, 3H), 1.73 (s, 3H)
756[Figure (not displayed)]
MS (ESI) m/z 541.2 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.42 (bs, 1H), 9.11 (bs, 1H), 8.89 (s, 1H), 7.76 (d, J = 2.16 Hz, 1H), 7.74-7.62 (m, 2H), 7.53-7.38 (m, 2H), 7.11 (t, J = 7.80 Hz, 1H), 4.46 (s, 2H), 4.23 (s, 2H), 2.62- 2.57 (m, 1H), 1.89 (s, 3H), 1.29-1.08 (m, 4H)
757[Figure (not displayed)]
MS (ESI) m/z 548.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (bs, 1H), 9.02 (s, 1H), 8.44 (d, J = 4.8 Hz 1H), 7.45 (dd, J = 2.8, 8.8 Hz, 1H), 7.26-7.20 (m, 3H), 4.31 (s, 4H), 2.62- 2.58 (m, 1H), 2.02 (s, 3H), 1.93 ( s, 3H), 1.20 (d, J = 8.0 Hz ,2H), 1.12 (s, 2H)
762[Figure (not displayed)]
MS (ESI) m/z 607.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.93 (s, 1H), 9.16 (s, 1H), 8.84 (d, J = 5.80, 2H), 7.91 (d, J = 5.92 Hz, 2H), 7.80 (s, 1H), 7.50 (dd, J = 8.84, 2.56 Hz, 1H), 7.29-7.26 (m, 3H), 7.15 (d, J = 7.32 Hz, 1H), 4.36 (t, J = 5.64, 2H), 4.25 (t, J = 3.80, 2H), 2.68 (s, 3H), 1.79 (s, 3H)
763[Figure (not displayed)]
MS (ESI) m/z 622.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 9.19 (s, 1H), 8.76 (d, J = 5.24, 1H), 7.89 (s, 1H), 7.85 (s, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.84, 2.52 Hz, 1H), 7.29-7.26 (m, 3H), 7.15 (d, J = 7.32 Hz, 1H), 4.36 (t, J = 3.96 Hz, 2H), 4.25 (t, J = 4.96 Hz 2H), 2.68 (s, 3H), 2.65 (s, 3H), 1.78 (s, 3H)
770[Figure (not displayed)]
MS (ESI) m/z 588.72 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.88 (d, J = 5.64 Hz, 2H), 8.79 (d, J = 4.76 Hz, 1H), 8.63 (s, 1H), 8.00 (d, J = 5.72 Hz, 2H), 7.77 (d, J = 8.08 Hz, 1H), 7.70-7.68 (m, J = 8.0 Hz, 2H) 7.55 (d, J = 4.76 Hz, 1H), 4.89 (s, 2H), 2.22 (s, 3H)
771[Figure (not displayed)]
MS (ESI) m/z 585.00 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.94 (bs, 1H), 8.94 (s, 1H), 7.76 (s, 1H), 7.48 (dd, J = 2.52, 8.76 Hz, 1H), 7.26-7.24 (m, 2H), 7.06 (s, 1H), 4.32 (t, J = 4.48 Hz, 2H), 4.20 (t, J = 5.08 Hz, 2H), 2.62- 2.59 (m, 1H), 2.49 (s, 3H), 2.33 (s, 3H), 1.75 (s, 3H), 1.22 (bs, 2H), 1.14 (bs, 2H)
772[Figure (not displayed)]
MS (ESI) m/z 588.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.70 (d, J = 5.12 Hz, 1H), 7.59 (dd, J = 8.88, 2.48 Hz, 1H), 7.42- 7.39 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.44 (t, J = 4.25 Hz, 2H), 4.29 (t, J = 4.28 Hz, 2H), 3.66 (s, 3H), 2.62-2.59 (m, 1H), 1.87 (s, 3H), 1.24- 1.19 (m, 4H)
773[Figure (not displayed)]
MS (ESI) m/z 590.98 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.98 (s, 1H), 7.83 (s, 1H), 7.53-7.49 (m, 2H), 7.33-7.22 (m, 3H), 4.34 (t, J = 4.8 Hz, 2H), 4.22 (t, J = 4.4 Hz, 2H), 2.60-2.58 (m, 1H), 1.77 (s, 3H), 1.22-1.15 (m, 4H)
791[Figure (not displayed)]
MS (ESI) m/z 574.95 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.57 (bs, 1H), 8.56 (s, 1H), 8.48 (s, 1H), 7.58 (dd, J = 8.8, 2.48 Hz, 1H), 7.41 (d, J = 2.52 Hz, 1H), 7.38 (s, 1H), 7.35 (d, J = 9.4 Hz, 1H), 4.39-4.36 (m, 2H), 4.21-4.18 (m, 2H), 3.25 (s, 6H), 2.70 (s, 3H), 1.80 (s, 3H)
792[Figure (not displayed)]
MS (ESI) m/z 565.91 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.84, 2.52 Hz, 1H), 7.42 (s, 2H), 7.34 (d, J = 8.96 Hz, 1H), 4.42-4.37 (m, 2H), 4.29-4.24 (m, 2H), 2.71 (s, 3H),.1.81(s, 3H)
793[Figure (not displayed)]
MS (ESI) m/z 585.97 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.39 (s, 1H), 7.61 (dd, J = 8.88, 2.68 Hz, 1H), 7.45-7.43 (m, 2H), 7.37 (d, J = 8.96 Hz, 1H), 4.41 (t, J = 5.08 Hz, 2H), 4.25 (t, J = 5.24 Hz, 2H), 3.02 (q, J = 7.56,7.52 Hz, 2H), 2.67 (bs, 1H), 1.83 (s, 3H), 1.35 (t, J = 7.52 Hz, 3H), 1.24-1.19 (m, 4H)
794[Figure (not displayed)]
MS (ESI) m/z 571.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 8.94 (s, 1H), 7.80 (s, 1H), 7.50 (dd, J = 8.84, 2.4 Hz, 1H), 7.26-7.21 (m, 3H), 7.12 (d, J = 7.32 Hz, 1H), 4.34 (t, J = 4.8 Hz, 2H), 4.21 (t, J = 4.44 Hz, 2H), 2.66 (s, 3H), 2.62-2.57 (m, 1H), 1.73 (s, 3H), 1.22-1.15 (m, 4H)
807[Figure (not displayed)]
MS (ESI) m/z 608.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.97 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45-7.40 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.45-4.35 (m, 2H), 4.26 (dtt, J = 14.9, 10.4, 5.0 Hz, 2H), 3.54 (td, J = 11.5, 7.9 Hz, 1H), 2.70 (s, 3H), 2.54- 2.44 (m,1H), 2.37-2.23 (m, 1H), 1.86 (s, 3H)
809[Figure (not displayed)]
MS (ESI) m/z 558.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.97 (d, J = 0.6 Hz, 1H), 8.41 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J = 9.0 Hz, 1H), 7.33-7.24 (m, 1H), 6.66 (dd, J = 16.7, 1.9 Hz, 1H), 5.88 (dd, J = 10.6, 1.9 Hz, 1H), 4.40 (t, J = 5.1 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 2.70 (s, 3H), 1.83 (s, 3H)
813[Figure (not displayed)]
MS (ESI) m/z 546.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.83 (d, J = 4.9 Hz, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.11 (q, J = 7.5 Hz, 2H), 1.81 (s, 3H), 1.34 (t, J = 7.5 Hz, 3H)
814[Figure (not displayed)]
MS (ESI) m/z 600.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.43 (s, 1H), 7.60 (dd, J = 9.0, 2.6 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.0 Hz, 2H), 4.16 (q, J = 10.7 Hz, 2H), 1.83 (s, 3H)
815[Figure (not displayed)]
MS (ESI) m/z 644.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.37 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 4.20- 4.24 (m, 2H), 3.60-3.40 (m, 2H), 3.30 (d, J = 14.1 Hz, 2H), 2.81 (d, J = 4.7 Hz, 3H), 1.79 (s, 3H), 1.43 (s, 3H), 1.38 (s, 3H)
816[Figure (not displayed)]
MS (ESI) m/z 644.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.58 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (s, 1H), 7.46 (d, J = 2.2 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.45-4.38 (m, 2H), 4.37- 4.28 (m, 2H), 4.22 (t, J = 5.1 Hz, 2H), 3.29-3.08 (m, 4H), 2.96 (d, J = 3.9 Hz, 3H), 1.76 (s, 3H), 1.68 (s, 3H), 1.48 (s, 3H)
817[Figure (not displayed)]
MS (ESI) m/z 660.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.8 Hz, 1H), 8.47 (d, J = 9.3 Hz, 2H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 4.91 (bs, 2H), 4.78 (bs, 2H), 4.49-4.38 (m, 2H), 4.30- 4.14 (m, 2H), 3.55-2.82 (br, 4H), 1.79 (s, 3H), 1.32-0.83 (m, 4H)
818[Figure (not displayed)]
MS (ESI) m/z 678.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.8 Hz, 1H), 8.49 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.9 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 6.26 (tt, J = 55.6, 4.2 Hz, 1H), 4.49-4.35 (m, 2H), 4.29- 4.12 (m, 2H), 3.25-2.72 (m, 8H), 1.75 (s, 3H), 0.64-0.53 (m, 2H)
819[Figure (not displayed)]
MS (ESI) m/z 617.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.36 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.59-4.58 (m, 2H), 4.40 (t, J = 5.1 Hz, 2H), 4.20 (t, J = 5.1 Hz, 2H), 3.84-3.76 (m, 1H), 3.66-3.54 (m, 2H), 1.91-1.84 (m, 2H), 1.78 (s, 3H), 1.53-1.41 (m, 2H)
820[Figure (not displayed)]
MS (ESI) m/z 699.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (dd, J = 4.9, 0.9 Hz, 1H), 8.71 (s, 1H), 8.42 (d, J = 1.5 Hz, 1H), 7.60 (dd, J = 9.0, 2.7 Hz, 1H), 7.50 (dd, J = 4.9, 2.6 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 5.37-5.27 (m, 1H), 4.39 (t, J = 5.0 Hz, 2H), 4.22 (t, J = 5.0 Hz, 2H), 3.43-3.26 (m, 2H), 3.02-2.90 (m, 2H), 2.81-2.69 (m, 2H), 2.12-2.01 (m, 2H), 1.90-1.79 (m, 2H), 1.75 (s, 3H)
821[Figure (not displayed)]
MS (ESI) m/z 680.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.50 (d, J = 4.8 Hz, 1H), 7.46 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.29 (t, J = 5.0 Hz, 2H), 4.05 (br, 2H), 3.62-3.16 (br, 6H), 2.89 (s, 3H), 1.77 (s, 3H)
822[Figure (not displayed)]
MS (ESI) m/z 648.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.71 (m, 2H), 8.66 (s, 1H), 7.75 (dd, J = 8.0, 0.9 Hz, 1H), 7.71-7.64 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.59 (bd, J = 16.5 Hz, 4H), 4.41 (s, 4H), 3.08 (br, 1H), 2.09 (s, 3H), 0.81-0.76 (m, 4H)
823[Figure (not displayed)]
MS (ESI) m/z 706.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.22 (t, J = 53.9 Hz, 1H), 4.56 (br, 6H), 4.38 (t, J = 5.0 Hz, 2H), 4.25 (br, 2H), 4.20 (t, J = 5.0 Hz, 2H), 1.79 (s, 3H), 1.32 (s, 6H)
824[Figure (not displayed)]
MS (ESI) m/z 678.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 4.9 Hz, 1H), 8.60 (s, 1H), 8.50 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.51 (d, J = 4.9 Hz, 1H), 7.45 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 6.26 (tt, J = 55.5, 4.2 Hz, 1H), 4.44-4.37 (m, 2H), 4.26- 4.14 (m, 2H), 3.44 (dd, J = 7.8, 6.6, 4.1 Hz, 2H), 3.19-2.84 (m, 6H), 1.74 (s, 3H), 0.81 (q, J = 6.6 Hz, 1H), 0.69-0.63 (m, 1H)
825[Figure (not displayed)]
MS (ESI) m/z 686.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 4.8 Hz, 1H), 8.57 (s, 1H), 8.44 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 4.65 (d, J = 48.5 Hz, 2H), 4.45 (br, 4H), 4.35 (t, J = 5.2 Hz, 2H), 4.27 (br, 4H), 4.17 (t, J = 5.2 Hz, 2H), 1.76 (s, 3H), 1.29 (br, 2H), 0.97 (br, 2H)
826[Figure (not displayed)]
MS (ESI) m/z 688.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.9 Hz, 1H), 8.61 (s, 1H), 8.48 (s, 1H), 7.64-7.58 (dd, J = 8.9, 2.6 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 4.4 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.71-4.42 (m, 8H), 4.38 (t, J = 5.2 Hz, 2H), 4.28-4.16 (m, 4H), 1.80 (s, 3H), 1.26 (s, 6H)
827[Figure (not displayed)]
MS (ESI) m/z 718.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.66 (s, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.59-4.47 (m, 2H), 4.33- 3.54 (br, 8H), 3.14 (s, 3H), 2.63 (br, 1H), 2.06 (s, 3H)
828[Figure (not displayed)]
MS (ESI) m/z 710.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.65 (s, 1H), 7.78-7.74 (m, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.53-4.45 (m, 1H), 4.49 (d, J = 47.2 Hz, 2H), 4.42-4.36 (m, 1H), 4.31-4.24 (m, 1H), 4.15-4.07 (m, 1H), 3.99-3.92 (m, 1H), 3.15 (s, 3H), 2.79-2.40 (m, 4H), 2.06 (s, 3H), 1.24 (d, J = 1.9 Hz, 6H)
829[Figure (not displayed)]
MS (ESI) m/z 682.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.58 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.45 (s, 2H), 4.37 (t, J = 5.1 Hz, 2H), 4.34 (s, 2H), 4.19 (t, J = 5.1 Hz, 2H), 3.98-3.87 (m, 1H), 2.76 (s, 3H), 2.69-2.42 (m, 4H), 1.76 (s, 3H), 1.10- 0.99 (m, 1H), 0.93-0.72 (m, 4H)
830[Figure (not displayed)]
MS (ESI) m/z 676.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.66 (s, 1H), 7.77-7.74 (m, 1H), 7.71-7.66 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.80 (s, 2H), 4.48 (s, 2H), 4.36 (s, 2H), 3.99- 3.88 (m, 1H), 2.76 (s, 3H), 2.70-2.42 (m, 4H), 2.08 (s, 3H), 1.09-0.99 (m, 1H), 0.92-0.72 (m, 4H)
831[Figure (not displayed)]
MS (ESI) m/z = 586.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.89 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 9.0, 2.6, 1H), 7.43-7.41 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 5.2 Hz, 2H), 4.39 (t, J = 5.2 Hz, 2H), 2.71 (s, 3H), 1.86 (s, 3H), 1.47 (s, 3H), 1.12-1.07 (m, 2H), 0.92-0.88 (m, 2H)
837[Figure (not displayed)]
MS (ESI) m/z = 652.1 [M + 1]+; 1H;-NMR (400 MHz, d6-DMSO) δ/ppm = 8.79 (d, J = 4.8 Hz, 1H), 8.48 (s, 1H), 8.46 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 7.38 (d, J = 2.7 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 4.94-4.81 (m, 2H), 4.40 (t, J = 4.6 Hz, 2H), 4.28-4.19 (m, 4H), 3.88-3.77 (m, 2H), 1.80 (s, 3H) [remaining CH2-protons presumably obscured by water-peak]
838[Figure (not displayed)]
MS (ESI) m/z = 666.4 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.81 (d, J = 4.8 Hz, 1H), 8.53 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 8.8, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.38 (d, J = 8.8 Hz, 1H), 4.85 (bt, J = 12.4 Hz, 2H), 4.42 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 4.24-4.14 (b, 2H), 2.87-2.71 (b, 3H), 1.83 (s, 3H), remaining protons appear to be obscured by water peak
839[Figure (not displayed)]
MS (ESI) m/z = 640.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.00 (s, 1H), 8.38 (s, 1H), 7.59 (dd, J = 8.9, 2.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.41 (s, 1H), 7.35 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.26 (t, J = 4.9 Hz, 2H), 2.70 (s, 3H), 1.90 (s, 3H), 1.63-1.58 (m, 2H), 1.54-1.48 (m, 2H)
840[Figure (not displayed)]
MS (ESI) m/z = 696.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.78 (d, J = 4.8 Hz, 1H), 8.55 (s, 1H), 8.44 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1H), 4.44 (s, 4H), 4.34 (t, J = 5.0 Hz, 2H), 4.15 (t, J = 5.0 Hz, 2H), 3.89-3.51 (b), 3.12-2.76 (b), 1.73 (s, 3H)
842[Figure (not displayed)]
MS (ESI) m/z = 610.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.98-9.88 (b, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.71-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.36 (bd, J = 14 Hz, 2H), 3.36-3.24 (m, 2H), 2.91 (s, 3H), 2.13 (s, 3H); remaining signals are obscured by water peak
843[Figure (not displayed)]
MS (ESI) m/z = 712.5 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.98-9.79 (b, 1H), 8.81 (d, J = 4.9 Hz, 1H), 8.52 (s, 1H), 8.49 (s, 1H), 7.61 (dd, J = 8.9, 2.8 Hz, 1H), 7.48 (d, J = 4.9 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1H), 5.21-5.08 (m, 2H), 4.43 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 3.76-3.62 (m, partially obscured by water peak), 3.38- 3.14 (m, partially obscured by water peak), 2.49-2.36 (m, 2H), 2.03-1.93 (m, 2H), 1.83 (s, 3H)
844[Figure (not displayed)]
MS (ESI) m/z = 712.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.98-9.78 (b, 1H), 8.83 (d, J = 4.9 Hz, 1H), 8.70 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.9 Hz, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.38 (d, J = 8.9 Hz, 1H), 4.41 (t, J = 4.8 Hz, 2H), 4.38- 4.28 (m, 2H), 4.24 (t, J = 4.8 Hz, 2H), 3.32-3.21 (m, partially obscured by water peak), 2.47- 2.33 (m, 2H), 2.02-1.91 (m,2 H), 1.85 (s, 3H); remaining signals obscured by water peak
845[Figure (not displayed)]
MS (ESI) m/z = 726.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 10.29-9.70 (b, 1H), 8.83 (d, J = 4.7 Hz, 1H), 8.71 (s, 1H), 8.44 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.7 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.41 (t, J = 4.5 Hz, 2H), 4.24 (t, J = 4.5 Hz, 2H), 4.50-3.20 (broad signals, partially obscured by water peak), 2.99 (bq, J = 11 Hz, 2H), 1.85 (s, 3H), 1.52 (s, 6H)
846[Figure (not displayed)]
MS (ESI) m/z 631.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.31 (s, 1H), 9.85 (s, 1H), 8.73 (d,J = 8.1 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (s, 1H), 7.40-7.33 (m, 2H), 5.69 (d, J = 7.2 Hz, 1H), 5.60-5.42 (m, 1H), 4.78 (s, 1H), 4.59-4.46 (m, 2H), 4.41 (t, J = 5.2 Hz, 2H), 4.29 (q, J = 5.9, 5.4 Hz, 3H), 3.04-2.96 (m, 3H), 2.71 (s, 3H), 2.54 (d, J = 6.4 Hz, 3H), 2.11 (d, J = 22.1 Hz, 3H)
848[Figure (not displayed)]
MS (ESI) m/z 671.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 7.56 (dd,J = 8.9, 2.7 Hz, 1H), 7.38-7.29 (m, 4H), 4.61- 4.42 (m, 1H), 4.36 (t, J = 5.0 Hz, 2H), 4.20 (t, J = 5.0 Hz, 2H), 3.18-3.09 (m, 2H), 3.04 (s, 3H), 2.78 (d, J = 4.6 Hz, 3H), 2.67 (s, 4H), 2.17- 1.94 (m, 3H), 1.92 (s, 3H)
850[Figure (not displayed)]
LCMS: 574.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.40-7.28 (m, 3H), 4.39 (t, J = 5.1 Hz, 2H), 4.22 (t, J = 5.0 Hz, 2H), 3.00 (q, J = 7.6 Hz, 2H), 2.70 (s, 3H), 2.66 (s, 3H), 1.90 (s, 3H), 1.28 (t, J = 7.5 Hz, 3H)
851[Figure (not displayed)]
LCMS: 560.4 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 4.8 Hz, 1H), 8.46 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.33 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 5.0 Hz, 2H), 4.21 (t, J = 5.0 Hz, 2H), 3.01 (q, J = 7.5 Hz, 2H), 2.71 (s, 3H), 1.80 (s, 3H), 1.28 (t, J = 7.5 Hz, 3H)
854[Figure (not displayed)]
MS (ESI) m/z 644.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 5.0 Hz, 2H), 4.21 (s, 2H), 3.08 (s, 3H), 2.81 (d, J = 4.7 Hz, 3H), 2.07 (d, J = 8.4 Hz, 5H), 1.77 (s, 3H)
857[Figure (not displayed)]
LCMS: 642.7 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.46 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.34 (m, 3H), 4.43 (t, J = 5.0 Hz, 2H), 4.24 (d, J = 5.0 Hz, 2H), 3.35 (t, J = 10.8 Hz, 3H), 2.79 (d, J = 3.4 Hz, 3H), 2.23 (s, 2H), 2.08 (d, J = 8.1 Hz, 2H), 1.86 (s, 3H)
860[Figure (not displayed)]
LCMS: 678.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81-8.73 (m, 2H), 8.66 (s, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.69 (dd, J = 6.2, 2.3 Hz, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.69 (t, J = 4.7 Hz, 4H), 3.30 (q, J = 10.2 Hz, 2H), 2.84 (t, J = 4.8 Hz, 4H), 2.07 (s, 3H)
861[Figure (not displayed)]
LCMS: 712.7 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.50 (s, 1H), 8.37 (s, 1H), 7.60 (dd, J = 9.0, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.69 (s, 1H), 4.43 (t, J = 5.1 Hz, 2H), 4.22 (d, J = 5.1 Hz, 2H), 3.22 (s, 1H), 3.13 (s, 3H), 3.04 (d, J = 11.2 Hz, 2H), 2.00-1.81 (m, 1H), 1.78 (s, 3H)
862[Figure (not displayed)]
LCMS: 662.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.45 (d, J = 9.3 Hz, J = 8.9, 2.7 Hz, 1H), 7.48-7.41 (m, 2H), 7.39 (d, J = 9.0 Hz, 1H), 5.50 (s, 1H),J = 11.4 Hz, 1H), 5.02 (d, J = 12.3 Hz, 1H), 4.44 (q, J = 4.8 Hz, 2H), J = 5.1 Hz, 2H), 3.85 (d, J = 12.3 Hz, 1H), 3.26 (d, J = 1.6 Hz, 3H), 2.87 (d, J = 4.1. 12H), 7.61 (dd, 5.38 (s, 1H), 5.10 (d, 4.25 (t, Hz, 3H), 2.20-2.03 (m, 1H), 1.80 (s, 3H)
863[Figure (not displayed)]
LCMS: 670.2 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.64 (s, 1H), 9.51 (s, 1H), 8.82- 8.75 (m, 1H), 8.44-8.38J = 8.9, 2.6 Hz, 1H), 7.49 (t, J = 5.0 Hz, 1H), 7.44 (dd, J = 9.0, 2.7 Hz, 1H),J = 9.0 Hz, 1H), 5.18 (dq, J = 11.7, 5.8 Hz, 1H), 5.05 (s, 1H), 4.44 (q, J = 5.2 Hz, 2H), J = 5.0 Hz, 2H), 4.05-3.78 (m, 2H), 3.17 (d, J = 9.9 Hz, 1H), 3.07 (s, 3H), 2.72-J = 3.4 Hz, 5H)
864[Figure (not displayed)]
LCMS: 694.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.9 Hz, 1H), 8.40 (d, J = 2.3 Hz, 2H), 7.58 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 7.40-7.32 (m, 2H), 6.55 (t, J = 52.5 Hz, 2H), 4.89 (s, 1H), 4.48- 4.32 (m, 2H), 4.21 (t, J = 5.3 Hz, 2H), 3.10 (s, 3H), 2.91 (s, 4H), 2.33-2.08 (m, 4H), 2.05- 1.88 (m, 3H), 1.74 (s, 3H)
865[Figure (not displayed)]
LCMS: 712.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.38 (t, J = 5.0 Hz, 2H), 4.33-4.13 (m, 3H), 3.07 (s, 3H), 2.73-2.52 (m, 3H), 2.03-1.82 (m, 2H), 1.77 (d, J = 28.9 Hz, 5H), 1.25 (d, J = 16.2 Hz, 1H)
866[Figure (not displayed)]
LCMS: 694.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 8.42 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.49 (d, J = 52.7 Hz, 1H), 4.64 (d, J = 15.0 Hz, 1H), 4.39 (t, J = 5.0 Hz, 2H), 4.22 (t, J = 5.1 Hz, 2H), 3.09 (s, 3H), 2.94 (s, 3H), 1.76 (s, 3H)
868[Figure (not displayed)]
MS (ESI) m/z 670.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.50 (s, 1H), 8.64 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.38-7.30 (m, 3H), 4.90 (s, 2H), 4.36 (t, J = 5.1 Hz, 2H), 4.22 (t, J = 5.1 Hz, 2H), 3.56 (d, J = 12.1 Hz, 2H), 3.30 (t, J = 10.9 Hz, 2H), 2.80 (s, 2H), 2.67 (s, 3H), 2.02 (d, J = 2.5 Hz, 4H), 1.93 (s, 3H)
869[Figure (not displayed)]
LCMS: 1.54 Min, 617.5 [M + H]-; 1H NM:R (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 8.80 (s, 1H), 8.72 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.44-7.33 (m, 3H), 5.62 (p, J = 6.2 Hz, 1H), 4.58-4.45 (m, 2H), 4.41 (t, J = 5.1 Hz, 2H), 4.25 (dt, J = 20.4, 5.8 Hz, 4H), 2.71 (s, 3H), 2.54 (s, 3H), 2.11 (s, 3H)
871[Figure (not displayed)]
LCMS (ESI) m/z 654.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.51-7.39 (m, 3H), 7.34 (d, J = 9.0 Hz, 1H), 7.26-7.14 (m, 2H), 4.43 (td, J = 8.9, 7.7, 3.7 Hz, 1H), 4.37 (dd, J = 10.3, 4.5 Hz, 1H), 4.23 (t, J = 5.1 Hz, 2H), 2.75 (s, 3H), 2.68 (s, 3H), 2.12 (s, 3H), 1.83 (s, 3H)
872[Figure (not displayed)]
LCMS (ESI) m/z 650.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.45 (m, 2H), 7.38 (d, J = 9.0 Hz, 1H), 7.30 (dd, J = 8.2, 6.9 Hz, 1H), 7.21-7.16 (m, 2H), 4.45 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 2.77 (s, 3H), 2.72 (s, 3H), 2.00 (s, 6H), 1.84 (s, 3H)
873[Figure (not displayed)]
LCMS (ESI) m/z 637.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.43 (m, 2H), 7.38 (d, J = 9.0 Hz, 1H), 7.30 (dd, J = 8.2, 6.9 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 4.45 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 4.9 Hz, 2H), 2.77 (s, 3H), 2.72 (s, 3H), 2.00 (s, 6H)
874[Figure (not displayed)]
LCMS (ESI) m/z 656.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.54 (s, 1H), 8.30 (dd, J = 9.3, 5.7 Hz, 1H), 7.66-7.57 (m, 2H), 7.48-7.33 (m, 3H), 6.96 (ddd, J = 8.2, 5.8, 2.3 Hz, 1H), 4.43 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 2.72 (d, J = 4.6 Hz, 6H), 1.87 (s, 3H)
875[Figure (not displayed)]
LCMS (ESI) m/z 644.1 [M + 1]+; 1H NMR (400 MHz, Chloroform-d) δ 8.48 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42-7.37 (m, 2H), 4.42 (d, J = 5.3 Hz, 2H), 4.33 (s, 1H), 4.30 (s, 1H), 4.25 (d, J = 5.0 Hz, 2H), 3.61 (d, J = 12.2 Hz, 2H), 3.44 (d, J = 13.6 Hz, 4H), 3.24 (d, J = 11.0 Hz, 1H), 2.92 (d, J = 4.4 Hz, 3H), 2.73 (s, 3H), 2.66 (s, 4H), 1.98 (s, 3H)
878[Figure (not displayed)]
LCMS (ESI) m/z 630.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.44 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.41-7.31 (m, 2H), 4.39 (d, J = 10.4 Hz, 1H), 4.39 (s, 1H), 4.20 (s, 1H), 3.79 (t, J = 4.9 Hz, 2H), 3.28 (s, 2H), 2.68 (s, 2H), 2.62 (s, 2H), 1.94 (s, 2H)
882[Figure (not displayed)]
LCMS (ESI) m/z 634.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.35 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.47-7.38 (m, 2H), 7.32 (d, J = 9.0 Hz, 1H), 6.27 (s, 1H), 4.37 (t, J = 5.0 Hz, 2H), 4.21 (t, J = 4.9 Hz, 2H), 2.87-2.75 (m, 4H), 2.22 (dq, J = 14.1, 6.8 Hz, 2H), 1.75 (s, 3H).
883[Figure (not displayed)]
LCMS (ESI) m/z 617.1 [M + 1]+.; 1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.47 (d, J = 0.8 Hz, 1H), 7.55 (dd, J = 8.9, 2.7 Hz, 1H), 7.41- 7.34 (m, 2H), 7.39-7.28 (m, 2H), 7.44-4.40 (m, 2H), 4.34 (t, J = 5.1 Hz, 2H), 4.16 (t, J = 5.1 Hz, 2H), 3.86 (dd, J = 11.5, 4.8 Hz, 2H), 3.73 (ddd, J = 11.1, 8.1, 3.4 Hz, 1H), 3.54 (d, J = 11.6 Hz, 1H), 2.67 (s, 3H), 2.05-1.94 (m, 1H), 1.90 (s, 2H), 1.76 (s, 3H)
884[Figure (not displayed)]
LCMS (ESI) m/z 614.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.45 (s, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.39-7.29 (m, 3H), 4.36 (t, J = 5.1 Hz, 2H), 4.24 (s, 2H), 4.22 − 4.14 (m, 4H), 2.71 (t, J = 7.7 Hz, 2H), 2.68 (s, 3H), 1.86 (s, 3H)
885[Figure (not displayed)]
LCMS (ESI) m/z 662.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.46 (s, 1H), 7.57 (dd, J = 9.0, 2.6 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 7.39-7.32 (m, 2H), 4.98-4.74 (m, 2H), 4.40 (t, J = 5.1 Hz, 2H), 4.29 (s, 2H), 4.21 (t, J = 5.1 Hz, 2H), 3.64 (s, 2H), 3.56 (s, 2H), 3.47 (s, 2H), 3.31 (s, 2H), 2.66 (s, 3H), 1.86 (s, 3H)
886[Figure (not displayed)]
LCMS (ESI) m/z 698.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.9 Hz, 1H), 8.54 (s, 1H), 7.60 (dd, J = 8.8, 2.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.41 (s, 2H), 4.21 (s, 2H), 3.65 (s, 5H), 3.29 (q, J = 10.2 Hz, 2H), 2.82 (s, 4H), 2.64 (s, 3H), 1.80 (s, 3H)
888[Figure (not displayed)]
LCMS (ESI) m/z 613.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 8.98 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (dd, J = 13.2, 3.7 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 6.51 (s, 1H), 4.40 (d, J = 5.3 Hz, 2H), 4.27 (d, J = 5.0 Hz, 2H), 4.14 (d, J = 17.9 Hz, 1H), 3.91 (s, 1H), 3.69 (d, J = 11.9 Hz, 1H), 3.35 (s, 1H), 2.95 (d, J = 4.5 Hz, 6H), 1.81 (s, 3H)
889[Figure (not displayed)]
1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.37 (s, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 15.4 Hz, 2H), 7.32 (d, J = 9.0 Hz, 1H), 6.40 (s, 1H), 4.37 (s, 2H), 4.21 (s, 2H), 3.35 (d, J = 9.9 Hz, 1H), 2.91 (s, 3H), 2.66 (s, 1H), 1.75 (s, 3H)
890[Figure (not displayed)]
LCMS (ESI) m/z 469.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.76-7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.51 (t, J = 54 Hz, 1H), 5.43 (s, 1H), 4.84 (s, 2H), 2.28 (s, 2H), 2.18 (s, 1H), 2.12 (s, 3H)
891[Figure (not displayed)]
LCMS (ESI) m/z 528.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 7.76 (d, J = 9.1 Hz, 1H), 7.72- 7.64 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 4.78 (s, 2H), 1.92 (s, 3H)
892[Figure (not displayed)]
LCMS (ESI) m/z 654.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 610.05 (s, 1H), 8.73-8.67 (m, 2H), 8.63 (s, 1H), 7.72 (dd, J = 8.1, 0.8 Hz, 1H), 7.73-7.61 (m, 2H), 7.51 (d, J = 4.8 Hz, 1H), 4.78 (s, 2H), 4.74-4.67 (m, 1H), 4.64- 4.55 (m, 3H), 4.49 (s, 2H), 4.40 (t, J = 6.9 Hz, 4H), 3.59 (d, J = 4.6 Hz, 1H), 3.52 (s, 1H), 2.07 (s, 3H), 1.21 (s, 1H)
893[Figure (not displayed)]
LCMS (ESI) m/z 672.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75-8.67 (m, 2H), 8.63 (s, 1H), 7.72 (dd, J = 8.1, 0.8 Hz, 1H), 7.69-7.61 (m, 2H), 7.51 (d, J = 4.8 Hz, 1H), 6.34 (t, J = 52 Hz, 1 H), 4.78 (s, 2H), 4.50 (s, 5H), 4.45 (s, 3H), 3.81 (s, 1H), 2.94 (s, 2H), 2.35 (s, 6H), 2.07 (s, 3H)
894[Figure (not displayed)]
LCMS (ESI) m/z 720.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.05(s, 1H), 8.75-8.71 (m, 2H), 8.66 (s, 1H), 7.78-7.73 (m, 1H), 7.72- 7.64 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.65 (s, 2H), 4.52 (s, 2H), 4.44 (d, J = 3.7 Hz, 4H), 4.37-4.29 (m, 2H), 3.61 (s, 2H), 2.10 (s, 3H)
895[Figure (not displayed)]
MS (ESI) m/z 650.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 8.85 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (dd, J = 8.4, 2.2 Hz, 1H), 7.66 (d, J = 2.1 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.38 (d, J = 14.1 Hz, 2H), 3.75 (d, J = 12.0 Hz, 2H), 3.60-3.48 (m, 2H), 3.33-3.23 (m, 2H), 3.17-3.11 (m, 2H), 2.14 (s, 3H), 1.18-1.08 (m, 1H), 0.72-0.66 (m, 2H), 0.45-0.37 (m, 2H)
897[Figure (not displayed)]
MS (ESI) m/z 562.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 8.72 (s, 1H), 8.42 (s, 1H), 7.58 (dd, J = 2.56, 8.72 Hz, 1H), 7.40 (bs, 2H), 7.34 (d, J = 8.92 Hz, 1H), 4.39 (t, J = 4.00 Hz, 2H), 4.39 (t, J = 4.52 Hz, 2H), 4.11 (s, 3H), 2.70 (s, 3H), 1.85 (s, 3H)
898[Figure (not displayed)]
MS (ESI) m/z 586.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 8.49 (s, 1H), 7.60-7.57 (dd, J = 4.0, 8.8 Hz, 1H), 7.39 (m, 3H), 4.44 (t, J = 6.0 Hz, 2H), 4.25 (t, J = 3.6 Hz, 2H), 2.68 (s, 6H), 1.90 (s, 3H), 1.18-1.16 (m, 4H)
900[Figure (not displayed)]
MS (ESI) m/z 572.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.39 (bs, 1H), 8.91 (s, 1H), 8.35 (s, 1H), 8.07 (s, 1H), 7.60-7.57 (dd, J = 7.48, 2.56 Hz, 1H), 7.41 (d, J = 2.52 Hz, 1H), 7.33 (d, J = 8.92 Hz, 1H), 4.41-4.35 (m, 2H), 4.30-4.20 (m, 2H), 3.01 (s, 3H), 2.67-2.60 (m, 1H), 1.81 (s, 3H), 1.28-1.12 (m, 4H)
910[Figure (not displayed)]
MS (ESI) m/z 648.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.41 (bs, 1H), 8.64 (s, 1H), 8.08 (d, J = 3.32 Hz, 2H), 7.58 (dd, J = 2.48, 8.84 Hz, 1H), 7.53 (d, J = 2.48 Hz, 3H), 7.42- 7.35 (d, J = 2.48 Hz, 1H), 7.35-7.38 (m, 2H), 4.43 (t, J = 5.80 Hz, 2H), 4.28 (t, J = 4.52 Hz, 2H), 2.66-2.55 (m, 1H), 2.55 (s, 3H), 1.95 (s, 3H), 1.23 (d, J = 4.28 Hz, 4H)
911[Figure (not displayed)]
MS (ESI) m/z 637.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 5.2 Hz, 1H), 8.47 (s, 1H), 7.83 (s, 1H), 7.79 (d, J = 4.48 Hz, 1H), 7.60 (dd, J = 2.52, 8.84 Hz, 1H), 7.42-7.34 (m, 3H), 4.45 (t, J = 6.12 Hz, 2H), 4.30 (t, J = 5.72 Hz, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 2.65 (s, 3H), 2.01 (s, 3H)
912[Figure (not displayed)]
MS (ESI) m/z 586.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.54 (s, 1H), 7.58 (dd, J = 8.92, 2.44 Hz, 1H), 7.42 (d, J = 2.52 Hz, 1H), 7.40 (s, 1H), 7.35 (d, J = 8.92 Hz, 1H), 4.95 (t, J = 8.68, 1H), 4.41 (t, J = 5.8 Hz, 2H), 4.24 (t, J = 5.84, 2H), 2.68 (s, 3H), 2.37- 2.32 (m, 3H), 2.13-2.08 (m, 2H), 1.91 (s, 3H), 1.91 (bs, 2H)
913[Figure (not displayed)]
MS (ESI) m/z 596.04 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (bs, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 7.58 (d, J = 8.68 Hz, 1H), 7.41 (s, 2H), 7.35 (d, J = 8.88 Hz, 1H), 4.40 (t, J = 4.88 Hz, 2H), 4.27 (t, J = 5.4 Hz, 2H), 2.70 (s, 3H), 2.16 (t, J = 19.28 Hz, 3H), 1.89 (s, 3H)
914[Figure (not displayed)]
MS (ESI) m/z 582.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 8.8, 2.5 Hz, 1H), 7.43-7.16 (m, 4H), 4.40 (t, J = 6.0 Hz, 2H), 4.28 (t, J = 2.6 Hz, 2H), 2.70 (s, 2H), 1.84 (s, 3H)
915[Figure (not displayed)]
MS (ESI) m/z 617.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.53 (bs, 1H), 9.02 (s, 1H), 8.36 (s, 1H), 7.59 (dd, J = 8.88 Hz, 2.52 Hz, 1H), 7.41-7.39 (m, 2H), 7.34 (d, J = 8.96 Hz, 1H), 5.72 (d, J = 47.16 Hz, 2H), 4.40 (t, J = 7.44 Hz, 2H), 4.27 (t, J = 4.48 Hz, 2H), 2.69 (s, 3H), 1.88 (s, 3H)
916[Figure (not displayed)]
MS (ESI) m/z 585.97 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.39 (s, 1H), 7.61 (dd, J = 8.88Hz, J = 2.68 Hz, 1H), 7.45- 7.43 (m, 2H), 7.37 (d, J = 8.96 Hz, 1H), 4.42- 4.39 (m, 2H), 4.26- 4.23 (m, 2H), 3.02 (q, J = 7.56 Hz, J = 7.52 Hz, 2H), 2.67 (s, 1H), 1.83 (s, 3H), 1.35 (t, J = 7.52 Hz, 3H), 1.24-1.19 (m, 4H)
917[Figure (not displayed)]
MS (ESI) m/z 590.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (s, 1H), 8.86 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 2.48, 8.88 Hz, 1H), 7.51 (s, 1H), 7.43 (d, J = 2.52 Hz, 1H), 7.35 (d, J = 8.96, 1H), 5.69 (d, J = 46.8 Hz, 2H), 4.40 (t, J = 3.96 Hz, 2H), 4.23 (t, J = 4.40 Hz, 2H), 2.61-2.57 (m, 1H), 1.77 (s, 3H), 1.23-1.15 (m, 4H)
922[Figure (not displayed)]
MS (ESI) m/z 540.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 8.87 (s, 1H), 7.74 (s, 1H) 7.67 (d, J = 2.3 Hz, 1H), 7.62 (dd, J = 8.84, 2.40 Hz, 1H), 7.35 (d, J = 8.92 Hz, 1H), 4.44 (s, 4H), 2.68 (s, 3H), 2.58-2.57 (m, 1H), 1.20-1.14 (m, 4H)
923[Figure (not displayed)]
MS (ESI) m/z 560.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.35 (s, 1H), 7.59-7.56 (dd, J = 2.4, 8.4 Hz, 1H), 7.41-7.33 (m, 3H), 4.40 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 3.12 (m, 2H), 2.68 (s, 3H), 1.88 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H)
924[Figure (not displayed)]
MS (ESI) m/z 690 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.4 (s, 1H), 8.50 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.89 (t, J = 7.2 Hz, 1H), 7.81 (t, J = 8.4 Hz, 1H), 7.61 (dd, J = 2.4, 8.8 Hz, 1H), 7.43 (s, 2H), 7.38 (d, J = 8.82 Hz, 1H), 4.44 (bs, 2H), 4.27 (bs, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 1.92 (s, 3H)
925[Figure (not displayed)]
MS (ESI) m/z 690.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.24 (s, 1H), 8.19 (d, J = 7.76 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.60 (dd, J = 2.56, 8.8 Hz, 1H), 7.43 (s, 1H), 7.39 (d, J = 2.2 Hz, 2H), 4.46 (t, J = 3.6 Hz, 2H), 4.30 (t, J = 4.4 Hz, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 2.00 (s, 3H)
926[Figure (not displayed)]
MS (ESI) m/z 690.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.44 (bs, 1H), 8.49 (s, 1H), 8.10 (d, J = 8.08 Hz, 2H), 7.95 (d, J = 8.20 Hz, 2H), 7.60 (dd, J = 8.88, 2.60 Hz, 1H), 7.43 (s, 1H), 7.42-7.37 (m, 2H), 4.45 (t, J = 4.64 Hz, 2H), 4.30 (t, J = 4.36 Hz, 2H), 2.80 (s, 3H), 2.71 (s, 3H), 1.99 (s, 3H)
927[Figure (not displayed)]
MS (ESI) m/z 654.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 8.48 (s, 1H), 7.60 (dd, J = 2.4, 8.7 Hz, 1H), 7.43-7.37 (m, 5H), 7.30-7.26 (m, 1H), 4.44 (t, J = 5.2 Hz, 2H), 4.27 (t, J = 5.8 Hz, 2H), 2.77 (s, 3H), 2.71 (s, 3H), 2.13 (s, 3H), 1.93 (s, 3H)
928[Figure (not displayed)]
MS (ESI) m/z 622.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.35 (s, 1H), 7.58 (dd, J = 2.52, 8.8 Hz, 1H), 7.39 (t, J = 2.68 Hz, 2H), 7.35 (d, J = 9 Hz, 1H), 4.39 (t, J = 4.4 Hz, 2H), 4.26 (t, J = 4.28 Hz, 2H), 4.04-3.95 (m, 1H), 3.11-3.05 (m, 4H), 2.70 (s, 3H), 1.91 (s, 3H)
929[Figure (not displayed)]
MS (ESI) m/z 636.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.04 (s, 1H), 8.37 (s, 1H), 7.61-7.56 (m, 1H), 7.44-7.38 (m, 2H), 7.34 (d, J = 8.96 Hz, 1H), 4.40-4.36 (m, 2H), 4.27-4.15 (m, 3H), 2.68 (s, 3H), 2.59-2.56 (m, 1H), 2.32-2.17 (m, 3H), 2.07-2.03 (m, 1H), 1.93-1.83 (m, 4H)
930[Figure (not displayed)]
MS (ESI) m/z 636.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 8.99 (s, 1H), 8.38 (s, 1H), 7.59 (dd, J = 8.88, 2.52 Hz, 1H),7.40 (s, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.41-4.36 (m, 2H), 4.31-4.23 (m, 2H), 4.08-4.02 (m, 1H), 2.70 (s, 3H), 2.63-2.57 (m, 2H), 2.38- 2.32 (m, 1H), 2.29-2.26 (m, 2H), 2.09-2.05 (m, 1H), 1.91 (s, 3H)
931[Figure (not displayed)]
MS (ESI) m/z 650.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.35 (s, 1H), 7.59 (dd, J = 8.88, 2.56 Hz, 1H), 7.44-7.40 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.68 Hz, 2H), 4.25 (t, J = 4.68, 2H), 3.60-3.50 (bs, 1H), 2.70 (s, 3H), 2.40-2.21 (m, 2H), 2.20-2.09 (m, 1H), 2.00.1.80 (m, 6H), 1.68-1.63 (m, 2H)
940[Figure (not displayed)]
MS (ESI) m/z 534.16 [M + 1]+;1H NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 8.82 (s, 1H), 7.61-7.56 (m, 2H), 7.36-7.26 (m, 3H), 6.73 (d, J = 7.88 Hz, 1H), 4.46-4.30 (m, 4H), 2.60-2.59 (m, merged, 1H), 2.57 (s, 3H), 1.28-1.10 (m, 4H)
941[Figure (not displayed)]
MS (ESI) m/z 626.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.56 (bs, 1H), 9.09 (s, 1H), 8.48 (s, 1H), 7.74-7.71 (m, 1H), 7.65-7.58 (m, 2H), 7.45-7.34 (m, 4H), 7.35 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 4.60 Hz, 2H), 4.28 (t, J = 4.60 Hz, 2H), 2.70 (s, 3H),1.90 (s, 3H)
942[Figure (not displayed)]
MS (ESI) m/z 626.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (bs, 1H), 9.04 (s, 1H), 8.38 (s, 1H), 7.74 (t, J = 6.92 Hz, 2H), 7.67- 7.58 (m, 2H), 7.45-7.41 (m, 3H), 7.36 (d, J = 8.76 Hz, 1H), 4.42 (t, J = 4.68 Hz, 2H), 4.28 (t, J = 4.08, Hz, 2H), 2.66 (s, 3H), 1.98 (s, 3H)
943[Figure (not displayed)]
MS (ESI) m/z 626.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (bs, 1H), 9.03 (s, 1H), 8.41 (s, 1H), 7.99-7.95 (m, 2H), 7.59 (dd, J = 2.56, 8.88 Hz, 1H), 7.45-7.41 (m, 4H), 7.36 (d, J = 8.96 Hz, 1H), 4.42 (t, J = 4.76 Hz, 2H), 4.28 (t, J = 4.52 Hz, 2H), 2.70 (s, 3H), 1.90 (s, 3H)
944[Figure (not displayed)]
MS (ESI) m/z 622.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 8.92 Hz, 2.64 Hz, 1H), 7.47-7.35 (m, 7H), 4.42 (t, J = 5.64 Hz, 2H), 4.27 (t, J = 4.4 Hz, 2H), 2.73 (s, 3H), 2.19 (s, 3H), 1.86 (s, 3H)
945[Figure (not displayed)]
MS (ESI) m/z 622.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.41 (s, 1H), 7.90 (s, 1H), 7.68 (s, 1H), 7.58 (dd, J = 8.2, 2.12 Hz, 1H), 7.48-7.35 (m, 5H), 4.42 (t, J = 4.48, 2H), 4.27 (t, J = 5.68, 2H), 2.71 (s, 3H), 2.43 (s, 3H), 1.88 (s, 3H)
946[Figure (not displayed)]
MS (ESI) m/z 622.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.5 (s, 1H), 9.027 (s, 1H), 8.40 (s, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.58 (dd, J = 2.56 Hz, J = 2.52 Hz, 1H), 7.34- 7.42 (m, 5H), 4.40-4.42 (bs, 2H), 4.26- 4.28 (bs, 2H), 2.70 (s, 3H), 2.42 (s, 3H), 1.87 (s, 3H)
947[Figure (not displayed)]
MS (ESI) m/z 642.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (bs, 1H), 9.07 (s, 1H), 8.43 (s, 1H), 7.70-7.68 (m, 2H), 7.66-7.54 (m, 3H), 7.43-7.42 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 6.16 Hz, 2H), 4.27 (t, J = 4.48 Hz, 2H), 2.71 (s, 3H), 1.88 (s, 3H)
948[Figure (not displayed)]
MS (ESI) m/z 642.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 9.03 (s, 1H), 8.37 (s, 1H), 7.97 (t, J = 2.0 Hz 1H), 7.90-7.84 (m, 1H), 7.67-7.58 (m, 3H), 7.42-7.40 (m, 2H), 7.41 (d, J = 2.6 Hz, 1H), 4.42 (t, J = 5.48 Hz, 2H), 4.28 (t, J = 4.40 Hz, 2H), 2.71 (s, 3H), 1.91 (s, 3H)
949[Figure (not displayed)]
MS (ESI) m/z 642.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.40 (s, 1H), 7.94 (d, J = 8.5 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H), 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.45-7.40 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.42 (t, J = 8.3 Hz, 2H), 4.28 (t, J = 4.4 Hz, 2H), 2.70 (s, 3H), 1.90 (s, 3H)
950[Figure (not displayed)]
MS (ESI) m/z 676 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.41 (s, 1H), 7.97 (d, J = 7.6 Hz, 1H), 7.91 (t, J = 7.6 Hz, 1H), 7.83 (t, J = 8.0 Hz, 2H), 7.61 (dd, J = 2.8, 8.8 Hz, 1H), 7.44 (s, 1H), 7.36 (d, J = 9.2 Hz) 1H), 4.42 (bs, 1H), 4.27 (bs, 1H), 2.72 (s, 3H), 1.87 (s, 3H)
951[Figure (not displayed)]
MS (ESI) m/z 676.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.37 (s, 1H), 8.27 (s, 1H), 8.22 (d, J = 7.6 Hz ,1H), 7.96 (d, J = 7.4 Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.60 (dd, J = 2.52, 8.8 Hz, 1H), 7.43 (s, 1H), 7.41 (d, J = 2.5 Hz ,1H), 7.37 (d, J = 8.9 Hz, 1H), 4.43 (t, J = 5.4 Hz, 2H), 4.29 (t, J = 4.96 Hz, 2H), 2.75 (s, 3H), 1.92 (s, 1H)
952[Figure (not displayed)]
MS (ESI) m/z 676.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.49 (bs, 1H), 9.07 (s, 1H), 8.41 (s, 1H), 8.13 (d, J = 8.16 Hz, 2H), 7.98 (d, J = 8.28 Hz, 2H), 7.60 (dd, J = 8.92, 2.60 Hz 1H), 7.43-7.40 (m, 2H), 7.36 (d, J = 8.96 Hz 1H), 4.42 (t, J = 6.48 Hz 2H), 4.29 (t, J = 4.48 Hz 2H), 2.71 (s, 3H), 1.92 (s, 3H)
953[Figure (not displayed)]
MS (ESI) m/z 655.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 6, 9.03(s, 1H), 8.33 (s, 1H), 7.62-7.58 ( m, 2H), 7.52 (dd, J = 2.16, 8.24 Hz, 1H), 7.47-7.42 (m, 3H), 7.37 (d, J = 8.92 Hz, 1H), 4.43 (t, J = 4.96 Hz, 2H), 4.29 (t, J = 3.88 Hz, 2H), 2.72 (s, 3H), 2.15 (s, 3H), 1.85 (s, 3H)
954[Figure (not displayed)]
MS (ESI) m/z 675.95 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.36 (s, 1H), 7.90 (s, 1H), 7.74-7.68 (m, 2H), 7.59 (d, J = 6.6 Hz, 1H), 7.42 (s, 2H), 7.35 (d, J = 8.8 Hz, 1H), 4.42 (s, 2H), 4.28 (s, 2H), 2.72 (s, 3H), 1.89 (s, 3H)
970[Figure (not displayed)]
MS (ESI) m/z 521.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (bs, 1H), 8.96 (s, 1H), 7.70 (s, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.17 (s, 1H), 7.10 (d, J = 8.8 Hz, 1H), 6.83 (s, 1H), 4.53 (t, J = 6.4 Hz, 2H), 4.39 (t, J = 4.8 Hz, 2H), 3.99 (s, 2H), 2.65 (s, 3H), 2.57 (bs, 1H), 1.20 (d, J = 7.6 Hz, 2H), 0.93 (d, J = 6.4 Hz, 2H)
971[Figure (not displayed)]
MS (ESI) m/z 643.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.38 (bs, 1H), 8.63 (s, 1H), 8.46 (s, 1H), 7.59 (dd, J = 2.5, 8.9 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (s, 1H), 7.34 (s, 1H), 4.76-4.69 (m, 2H), 4.38 (t, J = 4.3 Hz, 2H), 4.21 (t, J = 6.2 Hz, 2H), 3.43 (s, 3H), 2.69 (s, 3H), 1.81 (s, 3H)
972[Figure (not displayed)]
MS (ESI) m/z 629.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.43 (s, 1H), 7.77 (t, J = 6.0 Hz, 1H), 7.57 (d, J = 9.0 Hz, 1H), 7.41 (s, 1H), 7.35 (t, J = 5.3 Hz, 2H), 4.37- 4.30 (m, 4H), 4.20 (bs, 2H), 2.68 (s, 3H), 1.78 (s, 3H)
973[Figure (not displayed)]
MS (ESI) m/z 625.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.44 (s, 1H), 7.59 (dd, J = 2.56, 6.28 Hz, 1H), 7.40 (bs, 2H), 7.35 (d, J = 8.96 Hz, 1H), 6.38 (tt, J = 4.08, 59.88 Hz, 1H), 4.38 (t, J = 6.20 Hz, 2H), 4.21 (t, J = 4.48 Hz, 2H), 4.16-4.12 (m, 2H), 3.39 (s, 3H), 2.71 (s, 3H), 1.84 (s, 3H)
974[Figure (not displayed)]
MS (ESI) m/z 611.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.47 (s, 1H), 7.60-7.55 (m, 2H), 7.40 (s, 2H), 7.34 (d, J = 8.96 Hz 1H), 6.21 (tt, J = 5.28, 57.68 Hz, 1H), 4.36 (t, J = 4.60 Hz, 2H), 4.20 (t, J = 4.60 Hz, 2H), 3.93-3.86 (m, 2H), 2.70 (s, 3H), 1.80 (s, 3H)
975[Figure (not displayed)]
MS (ESI) m/z 560.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.61 (s, 1H), 7.62-7.59 (dd, J = 2.4, 8.4 Hz, 1H), 7.46 (s, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.88 (t, J = 9.6 Hz, 2H), 4.40 (t, J = 4.4 Hz, 2H), 4.23 (t, J = 4.8 Hz, 2H), 4.17 (t, J = 9.6 Hz, 2H), 3.52 (s, 1H), 2.66 (s, 3H), 1.86 (s, 3H)
976[Figure (not displayed)]
MS (ESI) m/z 591.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.23 (bs, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.38 (s, 1H), 7.33 (m, 2H), 4.37 (t, J = 5.2 Hz, 2H), 4.22 (t, J = 4.0 Hz, 2H), 3.84 (s, 3H), 3.26 (s, 3H), 2.66 (s, 3H), 1.63 (s, 3H)
977[Figure (not displayed)]
MS (ESI) m/z 615.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.44 (s, 1H), 7.59 (dd, J1 = 2.5 Hz, J2 = 8.8 Hz, 1H), 7.41- 7.40 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 8.8 Hz, 2H), 4.25 (t, J = 9.1 Hz, 2H), 4.08, (t, J = 13.6 Hz, 2H), 2.70 (s, 3H), 2.60-2.58 (m, 2H), 2.20 (t, J = 14.3 Hz, 2H), 1.87 (s, 3H)
978[Figure (not displayed)]
MS (ESI) m/z 604.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.48 (s, 1H), 7.59 (dd, J = 8.8 Hz, 2.48 Hz, 1H), 7.42-7.39 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.37 (d, J = 4.48 Hz, 2H), 4.19 (d, J = 4.8 Hz, 2H), 3.05 (s, 3H), 2.70 (s, 3H), 2.53 (s, 6H), 1.78 (s, 3H)
979[Figure (not displayed)]
MS (ESI) m/z 590.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.69 (bs, 1H), 8.57 (s, 1H), 8.46 (s, 1H), 7.59 (dd, J = 8.88 Hz, 2.44 Hz, 1H), 7.43-7.41 (m, 2H), 7.34 (d, J = 8.96 Hz, 1H), 4.36 (t, J = 4.28 Hz, 2H), 4.18 (t, J = 4.6 Hz, 2H), 2.70 (s, 9H), 1.71 (s, 3H)
980[Figure (not displayed)]
MS (ESI) m/z 716.23 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 3.60 Hz, 1H), 8.68 (s, 1H), 8.59 (s, 1H), 7.74 (d, J = 8.40 Hz, 1H), 7.67-7.64 (m, 2H), 7.43 (d, J = 3.60 Hz, 1H), 4.80 (s, 2H), 4.25 (bs, 1H), 3.83 (s, 3H), 3.10 (s, 3H), 3.02 (d, J = 9.6 Hz, 2H), 2.78-2.71 (m, 2H), 2.39-2.34 (m, 2H), 2.03 (s, 3H), 1.93- 1.91 (m, 2H), 1.76-1.05 (m, 5H)
981[Figure (not displayed)]
MS (ESI) m/z 554.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 9.19 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 7.61 (dd, J = 2.64, 8.88, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 2.68 Hz, 1H), 7.37 (d, J = 8.96 Hz, 1H), 6.72-6.46 (t, J = 51.6 Hz, 1H), 4.41 (d, J = 4.64 Hz, 2H), 4.36 (d, J = 4.52 Hz, 2H)
982[Figure (not displayed)]
MS (ESI) m/z 649.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 8.69 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 2.56 Hz, J = 8.88 Hz, 1H), 7.42-7.35 (m, 4H), 7.29 (d, J = 7.25 Hz, 1H), 7.12 (t, J = 7.52 Hz, 1H), 6.96 (t J = 7.24 Hz, 1H), 4.41 (t, J = 5.04 Hz, 2H), 4.34 (t, J = 8.04 Hz, 2H), 4.24 (t, J = 4.76 Hz, 2H), 3.22 (t, J = 7.88 Hz, 2H), 2.71 (s, 3H), 1.83 (s, 3H)
983[Figure (not displayed)]
MS (ESI) m/z 647.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.43 (s, 1H), 7.92 (d, J = 3.36 Hz, 1H), 7.74 (d, J = 8.12 Hz 1H), 7.69 (s, J = 7.60 Hz 1H), 7.61 (dd, J = 8.88, 2.48 Hz 1H), 7.45 (s, 1H), 7.43 (d, J = 2.48 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 7.29- 7.20 (m, 2H), 6.84 (d, J = 3.28 Hz, 1H), 4.44 (d, J = 4.48 Hz, 2H), 4.29 (d, J = 4.48 Hz, 2H), 2.70 (s, 3H), 1.87 (s, 3H)
984[Figure (not displayed)]
MS (ESI) m/z 598.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.58 (s, 1H), 8.44 (s, 1H), 7.96 (s, 1H), 7.59 (d, J = 8.76 Hz, 1H), 7.42 (s, 2H), 7.35 (d, J = 8.88 Hz, 1H), 6.70 (s, 1H), 4.41 (t, J = 4.12 Hz, 2H), 4.27 (t, J = 4.00 Hz, 2H), 2.71 (s, 3H), 1.83 (s, 3H)
985[Figure (not displayed)]
MS (ESI) m/z 561.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.52 (bs, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 7.58 (dd, J = 8.8, 2.12 Hz, 1H), 7.41 (s, 1H), 7.381H), 7.33 (d, J = 8.96 Hz, 1H), 7.28-7.20 (m, 1H), 4.36 (t, J = 5.68 Hz, 2H), 4.18 (t, J = 6.16 Hz, 2H), 2.97 (d, J = 4.24 Hz, 3H), 2.69 (s, 3H), 1.75 (s, 3H)
986[Figure (not displayed)]
MS (ESI) m/z 637.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 8.76 (s, 1H), 8.52 (s, 1H), 7.58 (dd, J = 8.84, 2.48 Hz, 1H), 7.43-7.32 (m, 5H), 7.18 (d, J = 8.00 Hz, 2H), 7.12 (t, J = 7.20 Hz, 1H), 4.35 (t, J = 5.48 Hz, 2H), 4.18 (t, J = 3.64 Hz, 2H), 3.53 (s, 3H), 2.72 (s, 3H), 1.78 (s, 3H)
987[Figure (not displayed)]
MS (ESI) m/z 651.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.45 (bs, 1H), 8.69 (s, 1H), 8.62 (s, 1H), 8.13 (t, J = 3.36 Hz, 2H), 7.58 (dd, J = 2.52, 8.84 Hz, 1H), 7.53-7.51 (m, 3H), 7.42 (d, J = 2.52 Hz, 1H), 7.39-7.36 (m, 2H), 4.41 (t, J = 4.60 Hz, 2H), 4.25 (t, J = 4.4 Hz, 2H), 3.31 (s, 6H), 2.56 (s, 3 H) 1.88 (s, 3H)
988[Figure (not displayed)]
MS (ESI) m/z 590.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.43-7.42 (m, 2H), 7.35 (d, J = 8.9 Hz, 1H), 4.95-4.90 (m, 1H), 4.39 (s, 2H), 4.23-4.20 (m, 2H), 3.22 (s, 3H), 2.70 (s, 3H), 1.84 (s, 3H), 1.50 (s, 3H)
989[Figure (not displayed)]
MS (ESI) m/z 626.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D2O) 6 9.14 (s, 1H), 7.79 (s, 1H), 7.50 (dd, J = 8.64 Hz, 1.96 Hz, 1H), 7.31 (d, J = 2.56 Hz, 1H), 7.25 (d, J = 8.68 Hz, 1H), 7.04 (s, 1H), 6.63 (s, 1H), 6.41 (s, 1H), 4.33 (s, 2H), 4.25 (s, 2H), 2.66 (s, 3H), 1.82 (s, 3H)
993[Figure (not displayed)]
MS (ESI) m/z 665.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.53 (bs, 1H), 9.56 (s, 1H), 9.11 (s, 1H), 8.72 (s, 1H), 8.32 (bs, 1H), 8.28 (d, J = 8.56 Hz, 1H), 8.06 (d, J = 8.48 Hz,1H), 7.59 (dd, J = 8.92Hz, 2.36 Hz, 1H), 7.41 (d, J = 2.28 Hz, 1H), 7.37-7.35 (m, 2H), 4.42 (t, J = 6.24 Hz, 2H), 4.30 (t, J = 4.56 Hz, 2H), 2.70 (s, 3H), 1.90 (s, 3H)
994[Figure (not displayed)]
MS (ESI) m/z 640.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.88, 2.62 Hz, 1H), 7.41 (t, J = 2.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 1H), 4.40 (t, J 5.2 Hz, 2H), 4.27 (t, J = 5.2 Hz, 2H), 2.94 (d, 4.4 Hz, 1H), 2.70 (s, 3H), 2.66- 2.60 (m, 1H), 1.91 (s, 3H), 1.68 (t, J = 7.2 Hz, 2H)
997[Figure (not displayed)]
MS (ESI) m/z 673.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 8.50 (s, 1H), 7.86 (dd, J = 2.56, 6.08 Hz, 1H), 7.70 (dd, J = 4.60, 8.60 Hz, 1H), 7.58 (dd, J = 2.52, 8.92 Hz, 1H), 7.49 (t, J = 9.28 Hz, 2H), 7.42-7.36 (m, 2H), 4.44 (t, J = 4.40 Hz, 2H), 4.29 (t, J = 4.40 Hz, 2H), 2.79 (s, 3H), 2.70 (s, 3H), 2.00 (s, 3H)
998[Figure (not displayed)]
MS (ESI) m/z 658.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 8.52 (s, 1H), 7.64-7.61 (m, 1H), 7.60 (dd, J = 2.4, 8.92 Hz, 1H), 7.50-7.47 (m, 2H), 7.42 (bs, 1H), 7.40 (d, J = 2.56 Hz, 1H), 7.37 (d, J = 9.00 Hz, 1H), 4.44 (t, J = 4.72 Hz, 2H), 4.29 (t, J = 4.52 Hz, 2H) 2.79 (s, 3H), 2.70 (s, 3H), 2.06 (s, 3H)
999[Figure (not displayed)]
MS (ESI) m/z 674.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 8.50 (s, 1H), 7.72-7.68 (m, 2H), 7.59 (dd, J = 2.56, 8.92 Hz, 1H), 7.53-7.45 (m, 1H), 7.43-7.41 (m, 2H), 7.34 (d, J = 9.2 Hz, 1H), 4.45 (t, J = 4.96 Hz, 2H), 4.29 (bs, 2H), 2.78 (s, 3H), 2.70 (s, 3H), 1.98 (s, 3H)
1004[Figure (not displayed)]
MS (ESI) m/z 548.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 2H), 8.51 (s, 1H), 8.30 (bs, 1H), 7.59 (dd, J = 8.88, 2.52 Hz, 1H), 7.42 (s, 2H), 7.34 (d, J = 9.00 Hz 1H), 4.35 (t, J = 5.48 Hz, 2H), 4.15 (t, J = 3.64 Hz, 2H), 2.71 (s, 3H), 1.65 (s, 3H)
1008[Figure (not displayed)]
MS (ESI) m/z 663.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.10-8.08 (m, 2H), 7.60 (dd, J = 2.4, 6.8 Hz, 2H), 7.51-7.50 (m, 3H), 7.41-7.36 (m, 3H), 4.42 (t, J = 4.8 Hz, 6H), 4.24 (t, J = 4.4 Hz, 2H), 2.57 (s, 3H), 2.42- 2.32 (m, 2H), 1.97 (s, 3H)
1010[Figure (not displayed)]
MS (ESI) m/z 617.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (s, 1H), 8.55 (s, 1H), 8.47 (s, 1H), 7.58 (d, J = 8.72 Hz ,1H), 7.40- 7.38 (m, 2H), 7.34 (d, J = 8.76 Hz, 1H), 4.55 (t, J = 6.76 Hz, 2H), 4.36 (m, 3H), 4.18-4.13 (m, 4H), 3.28 (s, 3H), 2.70 (s, 3H), 1.80 (s, 3H)
1011[Figure (not displayed)]
MS (ESI) m/z 603.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.48 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.39 (s, 1H ), 7.35 (d, J = 9.2 Hz 1H), 5.79 (d, J = 5.2 Hz, 1H), 4.58 (m, 3H), 4.36 (bs, 2H), 4.19 (bs, 2H), 4.07 (d, J = 6.8 Hz, 2H), 2.70 (s, 3H), 1.78 (s, 3H)
1015[Figure (not displayed)]
MS (ESI) m/z 636.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.67 (bs, 1H), 8.50 (s, 1H), 7.87 (m, 2H), 7.61-7.55 (m, 4H), 7.46 (s, 1H), 7.42 (d, J = 2.5 Hz, 1H), 7.37 (s, 1H), 4.45 (t, J = 5.3 Hz, 2H), 4.27 (t, J = 4.6 Hz, 2H), 3.04- 2.98 (m, 2H), 2.78 (s, 3H), 1.35 (s, 3H), 1.08 (t, J = 7.5 Hz, 3H)
1016[Figure (not displayed)]
MS (ESI) m/z 622.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.73 (bs, 1H), 9.02 (s, 1H), 8.39 (s, 1H) 7.94-7.87 (m, 2H), 7.61-7.58 (m, 4H), 7.46-7.43 (m, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.42 (t, J = 5.6 Hz, 2H), 4.27 (t, J = 4.32 Hz, 2H), 3.02 (q, J = 7.52 Hz, 2H), 1.83 (s, 3H) 1.35 (t, J = 7.56 Hz, 3H)
1037[Figure (not displayed)]
MS (ESI) m/z 688.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.86 (bs, 1H), 8.87 (s, 1H), 8.11 (s, 1H), 7.54 (d, J = 8.72 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J = 8.88 Hz, 1H), 7.23 (s, 1H), 4.48 (t, J = 4.4 Hz, 1H), 4.35 (t, J = 4.08, 2H), 4.22 (t, J = 3.24, 2H), 2.66 (s, 3H), 1.80 (s, 3H), 0.86 (d, J = 5.56 Hz, 2H), 0.81 (s, 2H)
1038[Figure (not displayed)]
MS (ESI) m/z 624.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.57 (bs, 1H), 8.62 (s, 1H), 8.44 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz 1H), 7.54-7.46 (m, 2H), 7.45-7.40 (m, 2H), 7.36 (d, J = 8.8 Hz, 1H), 7.35-7.28 m, 3H), 4.41 (t, J = 4.4 Hz, 2H), 4.26 (t, J = 5.2 Hz, 2H), 2.71 (s, 3H), 1.82 (s, 3H)
1039[Figure (not displayed)]
MS (ESI) m/z 639.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 1H), 8.71 (s, 1H), 8.59 (d, J = 4 Hz, 1H), 8.43 (s, 1H), 7.89 (t, J = 7.08 Hz, 1H), 7.60-7.57 (m, 2H), 7.40 (s, 2H), 7.39-7.34 (m, 2H), 5.68 (s, 2H), 4.40 (t, J = 5.36 Hz, 2H), 4.24 (t, J = 4.36 Hz,2H), 2.70 (s, 3H), 1.85 (s, 3H)
1041[Figure (not displayed)]
MS (ESI) m/z 653.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) ) 68.58 (s, 1H), 8.46 (s, 1H), 7.58 (dd, J = 2.4, 8.8 Hz, 1H), 7.40 (t, J = 2.4 Hz, 2H), 7.35 (d, J = 8.8 Hz, 1H), 7.03-6.65 (m, 1H), 5.12 (t, J = 3.6 Hz, 1H), 4.72 (m, 2H), 4.38 (t, J = 5.2 Hz, 2H), 4.32 (m, 2H), 4.21 (t, J = 4.4 Hz, 2H), 3.40 (s, 1H), 2.71 (s, 3H), 1.83 (s, 3H)
1042[Figure (not displayed)]
MS (ESI) m/z 671.16 [M + 1]-; 1H NMR (400 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 2.8, 8.8 Hz, 1H), 7.41-7.40 (m, 2H), 7.36 (d, J = 8.8 Hz, 1H), 5.36-5.33 (m, 1H), 4.79-4.75 (m, 2H), 4.43 (t, J = 3.2 Hz, 2H), 4.40 (t, J = 7.6 Hz, 2H), 4.21 (d, J = 4.4 Hz, 2H), 2.17 (s, 3H), 1.85 (s, 3H)
1043[Figure (not displayed)]
MS (ESI) m/z 667.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.47 (s, 1H), 7.57 (dd, J = 2.52, 8.8 Hz ,1H), 7.40 (t, J = 2.4 Hz, 2H), 7.34 (d, J = 8.84 Hz, 1H), 6.35-6.06 (m, 1H), 4.59 (t, J = 6.24 Hz, 2H), 4.36 (t, J = 4.8 Hz, 2H), 4.18 (d, J = 6.8 Hz, 4H), 3.84-3.75 (m, 2H), 2.70 (s, 3H), 1.80 (s, 3H)
1044[Figure (not displayed)]
MS (ESI) m/z 685.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.58 (bs, 1H), 8.57 (s, 1H), 8.47 (s, 1H), 7.58 (dd, J = 2.48, 8.88 Hz ,1H), 7.40 (d, J = 2.56 Hz, 1H), 7.39 (s, 1H), 7.34 (d, J = 9.00 Hz, 1H), 4.65-4.58 (m, 3H), 4.37 (t, J = 6.08 Hz, 2H), 4.25-4.19 (m, 6H), 2.70 (s, 3H), 1.81 (s, 3H)
1045[Figure (not displayed)]
MS (ESI) m/z 659.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 8.55 (s, 1H), 8.47 (s, 1H), 7.59 (dd, J = 2.48, 8.84 Hz, 1H), 7.41 (d, J = 2.52 Hz, 1H), 7.39 (s, 1H), 7.34 (d, J = 8.96 Hz, 1H), 4.68-4.65 (m, 1H), 4.61-4.57 (m, 2H), 4.34 (t, J = 4.68 Hz, 2H), 4.16 (t, J = 3.72 Hz, 2H), 4.06-4.03 (m, 2H), 2.67 (s, 3H), 1.82 (s, 3H), 1.15 (s, 9H)
1051[Figure (not displayed)]
MS (ESI) m/z 641.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.52 (s, 1H), 9.06 (s, 1H), 8.67 (d, J = 2.76 Hz, 1H), 8.36 (s, 1H), 8.06 (dd, J = 2.64, 9.0 Hz, 1H), 7.60 (dd, J = 2.52, 8.8 Hz ,1H), 7.43 (s, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.43 (t, J = 5.0 Hz, 2H), 4.29 (t, J = 5.5 Hz, 2H), 2.72 (s, 3H), 2.36 (s, 3H), 1.91 (s, 3H)
1052[Figure (not displayed)]
MS (ESI) m/z, 640.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.51 (bs, 1H), 9.03 (s, 1H), 8.37 (s, 1H), 7.60 (dd, J = 2.40, 8.84 Hz, 1H), 7.43 (bs, 4H), 7.34 (d, J = 8.92 Hz, 1H), 7.32- 7.28 (m, 1H), 4.42 (t, J = 4.72 Hz, 2H), 4.27 (t, J = 4.76 Hz, 2H), 2.72 (s, 3H), 2.14 (s, 3H), 1.86 (s, 3H)
1053[Figure (not displayed)]
MS (ESI) m/z 603.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.38 (s, 1H), 7.59 (d, J = 8.72 Hz, 1H), 7.42 (s, J = 2.76, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.41 (s, 2H), 4.26 (s, 2H), 3.34 (s, 3H), 2.71 (s, 3H), 2.00 (bs, 3H), 1.84 (s, 3H)
1056[Figure (not displayed)]
MS (ESI) m/z 617.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.50 (s, 1H), 7.59 (dd, J = 8.8 Hz, 2.44 Hz, 1H), 7.42-7.40 (m, 2H), 7.35 (d, J = 9 Hz, 1H), 4.38 (bs, 1H), 4.36 (m, 2H), 4.21-4.18 (m, 2H), 3.93-3.87 (m, 3H), 3.78-3.73 (m,1H), 3.56 (d, J = 11.68 Hz, 1H), 2.70 (s, 3H), 2.04-2.02 (m, 1H), 1.94-1.92 (m, 1H), 1.79 (s, 3H)
1057[Figure (not displayed)]
MS (ESI) m/z 617.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 8.56 (s, 1H), 8.47 (s, 1H), 7.58 (d, J = 8.64 Hz, 1H), 7.40 (d, J = 8.84 Hz, 2H), 7.34 (d, J = 8.88 Hz, 1H), 5.70 (bs, 1H) 4.36 (t, J = 6.56 Hz, 2H), 4.20 (m, 6H), 2.70 (s, 3H), 1.77 (s, 3H), 1.47 (s, 3H)
1062[Figure (not displayed)]
MS (ESI) m/z 574.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.7 (bs, 1H), 8.92 (s, 1H), 8.35 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.44-7.43 (m, 2H), 7.36 (d, J = 8.8 Hz, 1H), 4.40 (t, J = 4.4 Hz, 2H), 4.25 (t, J = 4.0 Hz, 2H), 3.12- 3.07(m, 2H), 3.03-2.97 (m, 2H), 1.83 (s, 3H), 1.36 (t, J = 7.2 Hz, 6H)
1063[Figure (not displayed)]
MS (ESI) m/z 573.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.30 (s, 1H), 7.55 (dd, J = 8.88 Hz, 2.32 Hz, 1H), 7.35-7.30 (m, 3H), 4.36 (t, J = 6.6 Hz, 2H), 4.22 (t, J = 5.12 Hz, 2H), 3.02 (t, J = 7.36 Hz, 2H), 2.71 (s, 3H), 1.90 (s, 3H), 1.80-1.74 (m, 2H),0.93 (t, J = 14.6Hz, 3H)
1064[Figure (not displayed)]
MS (ESI) m/z 578.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 8.88 Hz, 2.62 Hz, 1H), 7.41 (s, 2H), 7.35 (d, J = 8.89 Hz, 1H), 4.94 (dt, J = 48 Hz, 6.0 Hz, 2H), 4.40 (t, J = 5.2 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 3.49 (dt, J = 25 Hz, 6.0 Hz, 2H), 2.70 (s, 3H), 1.89 (s, 3H)
1065[Figure (not displayed)]
MS (ESI) m/z 578.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 9.03 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.8, 2.2 Hz 1H), 7.45-7.38 (m, 2H), 7.35 (d, J = 8.92 Hz, 1H), 6.24-6.15 (dq, J = 47.20, 6.80 Hz, 1H), 4.47- 4.35 (m, 2H), 4.35-4.29 (m, 2H), 2.69 (s, 3H), 1.87 (s, 3H), 1.78 (dd, J = 24.4, 6.32 Hz, 3H)
1066[Figure (not displayed)]
MS (ESI) m/z 576.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.58 (s, 1H), 8.98 (s, 1H), 8.35 (s, 1H), 7.58 (s, 1H), 7.41-7.35 (m, 3H), 4.74 (s, 2H), 4.39 (s, 2H), 4.26 (s, 2H), 3.38 (s, 3H) 2.69 (s, 3H), 1.85 (s, 3H)
1067[Figure (not displayed)]
MS (ESI) m/z 576.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.42 (s, 1H), 7.57 (dd, J = 2.52, 8.8 Hz, 1H), 7.41 (s, 2H), 7.35 (d, J = 8.92 Hz, 1H), 4.59-4.54 (m, 2H), 4.39 (t, J = 4.4 Hz, 2H), 4.23 (t, J = 4.3 Hz, 2H), 2.71 (s, 3H), 1.84 (s, 3H)
1068[Figure (not displayed)]
MS (ESI) m/z 602.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 8.69 (s, 1H), 8.37 (s, 1H), 7.59 (dd, J = 8.88, 2.64 Hz, 1H), 7.40 (d, J = 2.60 Hz, 1H), 7.38 (s, 1H), 7.34 (d, J = 8.96 Hz, 1H), 4.41-4.31 (m, 4H), 4.23 (t, J = 4.60 Hz, 2H), 2.70 (s, 3H), 1.83 (s, 3H), 1.40- 1.40 (m, 1H), 0.65-0.58 (m, 2H), 0.46-0.39 (m, 2H)
1068[Figure (not displayed)]
MS (ESI) m/z 561.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 8.55 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.40-7.34 (m, 3H), 7.03 (s, 2H), 4.38 (t, J = 5.9 Hz, 2H), 4.17 (t, J = 4.0 Hz, 2H), 2.69 (s, 3H), 2.56 (s, 3H), 1.72 (s, 3H)
1070[Figure (not displayed)]
MS (ESI) m/z 575.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 7.60 (dd, J = 2.0, 8.8 Hz, 1H), 7.44 (t, J = 3.6 Hz, 2H), 7.36 (d, J = 9.2 Hz, 1H), 7.03 (bs, 2H), 4.40 (bs, 2H), 4.17 (bs, 2H), 3.03 (m, 2H), 2.55 (s, 3H), 1.69 (s, 3H), 2.96 (t, J = 7.6 Hz, 3H)
1071[Figure (not displayed)]
MS (ESI) m/z 561.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 8.47 (s, 1H), 8.44 (s, 1H) 7.59 (d, J = 9.20 Hz, 1H), 7.44 (s, 2H), 7.33 (d, J = 9.0 Hz, 1H), 7.21 (bs, 2H), 4.35 (t, J = 5.48 Hz, 2H), 4.16 (t, J = 6.28 Hz, 2H), 3.01 (q, J = 7.52 Hz, 2H), 1.64 (s, 3H), 1.34 (t, J = 7.48 Hz, 3H)
1072[Figure (not displayed)]
MS (ESI) m/z 547.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.47 (s, 1H) 7.59 (dd, J = 8.92, 2.44 Hz, 1H), 7.45-7.39 (m, 2H), 7.33 (d, J = 8.92 Hz 1H), 7.21 (bs, 2H), 4.36 (t, J = 6.0 Hz, 2H), 4.17 (t, J = 6.04 Hz, 2H), 2.70 (s, 3H), 1.68 (s, 3H)
1076[Figure (not displayed)]
MS (ESI) m/z 600.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H), 8.81 (s, 1H), 8.35 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.43 (s, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.41 (t, J = 4.8 Hz, 2H), 4.24 (t, J = 4.4 Hz, 2H), 2.96 (t, J = 7.2 Hz, 2H), 2.66 (m, 1H), 1.85-1.75 (m, 5H), 1.23-1.18 (m, 2H), 1.10-1.06 (m, 2H), 1.00 (t, J = 7.2 Hz, 3H)
1086[Figure (not displayed)]
MS (ESI) m/z 644.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 9.90 (bs, 1H), 8.66 (s, 1H), 8.38 (s, 1H) 7.60 (dd, J = 8.88, 2.36 Hz, 1H), 7.46 (s, 1H), 7.41 (d, J = 2.36 Hz 1H), 7.37 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.88 Hz, 2H), 4.31 (d, J = 13.92 Hz, 2H), 4.22 (t, J = 5.84 Hz, 2H), 3.61 (d, J = 11.36 Hz, 2H), 3.44 (t, J = 11.92 Hz, 2H), 3.30-3.28 (m, 2H), 3.02 (q, J = 7.44 Hz, 2H), 2.91 (s, 3H), 1.84 (s, 3H), 1.37 (t, J = 7.52 Hz, 3H)
1089[Figure (not displayed)]
MS (ESI) m/z 586.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 8.75 (s, 1H), 7.68 (s, 1H), 7.52 (d, J = 7.0 Hz, 1H), 7.34-7.28 (m, 3H), 7.09 (s, 1H), 4.34(5, 2H), 4.20 (s, 2H), 3.65 (s, 4H), 2.58 (s, 4H), 2.49 (s, 3H), 2.24 (s, 3H), 1.8 (s, 3H)
1091[Figure (not displayed)]
MS (ESI) m/z 644.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.39 (bs, 1H), 8.62 (s, 1H), 7.59 (dd, J = 2.48, 8.88 Hz ,1H), 7.40-7.38 (m, 2H), 7.35 (d, J = 8.92 Hz, 1H), 4.63-4.59 (m, 2H), 4.47 (bs, 2H), 4.39 (t, J = 4.64 Hz, 2H), 4.23 (t, J = 4.64 Hz, 3H), 2.82 (bs, 6H), 2.70 (s, 3H), 2.54 (s, 3H), 1.94 (s, 3H)
1092[Figure (not displayed)]
MS (ESI) m/z 670.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.33-7.30 (m, 3H), 4.88 (s, 2H), 4.35 (s, 2H), 4.22 (s, 2H), 3.53 (d, J = 12 Hz, 2H), 3.31 (d, J = 11.6 Hz, 2H), 2.79 (s, 3H), 2.66 (s, 3H), 2.46 (s, 3H), 2.05 (s, 7H)
1097[Figure (not displayed)]
MS (ESI) m/z 651.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.42 (s, 1H), 7.59 (dd, J = 8.8, 2.56 Hz, 1H), 7.41 (s, 2H), 7.36 (d, J = 8.95 Hz, 1H), 4.39 (t, J = 6.9 Hz, 2H), 4.22 (t, J = 4.56 Hz, 2H), 3.87-3.75 (m, 4H), 2.71 (s, 3H), 2.21-2.15 (m, 4H) 1.87 (s, 3H)
1099[Figure (not displayed)]
MS (ESI) m/z 325.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 7.39-7.28 (m, 5H), 7.19 (d, J = 7.9 Hz, 1H), 4.99 (s, 2H), 3.50 (t, J = 12.4 Hz, 4H), 3.29-3.17 (m, 1H), 2.04 (t, J = 10.8 Hz, 2H), 1.77 (d, J = 12.4 Hz, 2H), 1.70 (d, J = 12.8 Hz, 2H), 1.15 (dq, J = 12.9, 3.2 Hz, 2H), 0.99 (q, J = 13.3 Hz, 2H)
1100[Figure (not displayed)]
MS (ESI) m/z 714.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.7 Hz, 1H), 8.71 (s, 1H), 8.66 (s, 1H), 7.78-7.74 (m, 1H), 7.69 (dd, J = 6.4, 2.2 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.92 (br, 4H), 4.82 (s, 2H), 4.33 (br, 2H), 3.13 (s, 3H), 2.07 (s, 3H), 2.03-1.61 (m, 8H)
1101[Figure (not displayed)]
MS (ESI) m/z 670.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.77 (s, 1H), 8.36 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (br, 2H), 4.23 (br, 2H), 3.81-3.03 (br, 6H), 1.79 (s, 3H), 1.62 (br, 3H), 1.31 (br, 4H), 0.96-0.75 (m, 4H)
1102[Figure (not displayed)]
MS (ESI) m/z 664.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 7.78-7.73 (m, 1H), 7.69 (dd, J = 6.6, 2.2 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.85 (d, J = 7.1 Hz, 2H), 3.83-2.97 (br, 6H), 2.12 (s, 3H), 1.63 (br 3H), 1.34 (br, 3H), 1.23-0.78 (m, 5H)
1103[Figure (not displayed)]
MS (ESI) m/z 738.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.66 (s, 1H), 7.78-7.73 (m, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.79-6.41 (m, 1H), 4.82 (s, 2H), 4.36 (br, 1H), 3.11 (s, 3H), 2.07 (s, 3H), 2.05-1.82 (br, 2H). Protons on piperidine were not seen
1104[Figure (not displayed)]
MS (ESI) m/z 722.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.74 (d, J = 4.7 Hz, 1H), 8.62 (s, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.71-7.61 (m, 2H), 7.43 (d, J = 4.7 Hz, 1H), 4.82 (s, 2H), 4.54 (bs, 2H), 3.86 (s, 3H), 3.68- 3.23 (br, 2H), 2.15 (s, 3H). Some aliphatic protons were not seen
1105[Figure (not displayed)]
MS (ESI) m/z 829.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.9 Hz, 1H), 8.82 (s, 1H), 8.75 (s, 1H), 7.78 (d, J = 9.1 Hz, 1H), 7.71 (dd, J = 6.6, 2.2 Hz, 2H), 7.64 (d, J = 4.9 Hz, 1H), 7.26-6.94 (m, 1H), 6.59 (tt, J = 54.1, 4.3 Hz, 2H), 4.84 (s, 2H), 4.56 (br, 1H), 4.48 (td, J = 14.7, 4.3 Hz, 2H), 3.12 (s, 3H), 2.34-1.97 (br, 8H), 1.95 (s, 3H), 1.76 (t, J = 19.4 Hz, 3H)
1106[Figure (not displayed)]
MS (ESI) m/z 710.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 8.66 (s, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 5.00-4.86 (m, 1H), 4.83 (s, 2H), 4.81-4.68 (m, 1H), 3.78-3.29 (m, 2H), 3.19 (s, 3H), 2.87 (s, 3H), 2.44-2.11 (m, 5H), 2.08 (s, 3H), 2.06-1.77 (m, 5H)
1107[Figure (not displayed)]
MS (ESI) m/z 752.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 8.66 (s, 1H), 7.78-7.74 (m, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.9 Hz, 1H), 4.82 (s, 2H), 4.38 (br, 1H), 3.11 (s, 3H), 2.08 (s, 3H), 2.07-1.92 (br, 2H), 1.84 (t, J = 20.0 Hz, 3H). Piperidine protons were not seen
1108[Figure (not displayed)]
MS (ESI) m/z 791.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.82-8.78 (m, 2H), 8.76 (s, 1H), 7.77 (dd, J = 8.3, 0.6 Hz, 1H), 7.73-7.66 (m, 2H), 7.62 (d, J = 4.9 Hz, 1H), 4.83 (s, 2H), 4.78 (br, 4H), 4.36-4.22 (m, 2H), 3.54 (s, 3H), 3.09 (s, 3H), 2.12-2.02 (m, 2H), 1.98 (s, 3H), 1.80-1.67 (m, 3H), 1.46-1.32 (m, 3H)
1109[Figure (not displayed)]
MS (ESI) m/z 854.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (s, 1H), 8.89 (d, J = 4.8 Hz, 1H), 8.72 (ddd, J = 4.6, 1.7, 0.9 Hz, 1H), 8.66 (s, 1H), 8.59 (s, 1H), 8.27 (dt, J = 8.0, 1.1 Hz, 1H), 8.25-8.18 (m, 1H), 7.79-7.72 (m, 2H), 7.72-7.68 (m, 2H), 7.66 (d, J = 4.9 Hz, 1H), 4.82 (s, 2H), 4.76 (br, 4H), 4.34-4.23 (m, 1H), 3.24 (br, 1H), 3.07 (s, 3H), 2.13-2.01 (m, 2H), 1.97 (br, 2H), 1.94 (s, 3H), 1.71 (q, J = 12.1 Hz, 2H), 1.38 (q, J = 12.0 Hz, 2H)
1110[Figure (not displayed)]
MS (ESI) m/z 854.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.29 (dd, J = 2.4, 0.8 Hz, 1H), 8.92 (dd, J = 4.8, 1.6 Hz, 1H), 8.83 (d, J = 4.9 Hz, 1H), 8.69 (s, 1H), 8.54 (ddd, J = 8.2, 2.4, 1.6 Hz, 1H), 8.47 (s, 1H), 7.77-7.67 (m, 3H), 7.66 (dd, J = 2.2, 0.5 Hz, 1H), 7.62 (dd, J = 4.8, 0.4 Hz, 1H), 4.84 (br, 4H), 4.80 (s, 2H), 4.39-4.27 (m, 1H), 3.28 (br, 1H), 3.09 (s, 3H), 2.14-2.05 (m, 2H), 2.02-1.94 (m, 2H), 1.91 (s, 3H), 1.74 (q, J = 12.2 Hz, 2H), 1.42 (q, J = 11.9 Hz, 2H)
1111[Figure (not displayed)]
MS (ESI) m/z 854.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.98-8.93 (m, 2H), 8.84 (d, J = 4.9 Hz, 1H), 8.70 (s, 1H), 8.48 (s, 1H), 8.11- 7.70 (dd, J = 8.4, 2.2 Hz, 1H), 7.66 (dd, J = 2.2, 0.5 Hz, 1H), 7.64 (dd, J = 4.9, 0.4 Hz, 1H), 4.84 (br, 4H), 4.81 (s, 2H), 4.38-4.25 (m, 1H), 3.28 (br, 1H), 3.08 (s, 3H), 2.15-2.06 (m, 2H), 2.01-1.94 (m, 2H), 1.92 (s, 3H), 1.73 (q, J = 12.1 Hz, 2H), 1.41 (q, J = 11.8 Hz, 2H)
1112[Figure (not displayed)]
MS (ESI) m/z 688.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.77-7.74 (m, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.52 (t, J = 53.4 Hz, 1H), 4.83 (s, 2H), 4.50 (bs, 1H), 3.11 (s, 3H), 2.25-1.98 (m, 7H)
1113[Figure (not displayed)]
MS (ESI) m/z 702.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.7 Hz, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 7.74 (dd, J = 8.1, 0.8 Hz, 1H), 7.68-7.64 (m, 2H), 7.44 (d, J = 4.7 Hz, 1H), 6.15 (tt, J = 55.8, 4.4 Hz, 1H), 4.81 (s, 2H), 4.26 (ddt, J = 11.6, 7.7, 4.0 Hz, 1H), 3.84 (s, 3H), 3.10 (s, 3H), 3.03 (d, J = 11.2 Hz, 2H), 2.76 (td, J = 15.7, 4.3 Hz, 2H), 2.33 (t, J = 11.5 Hz, 2H), 2.03 (s, 3H), 1.92 (qd, J = 12.1, 3.9 Hz, 2H), 1.79 (d, J = 11.7 Hz, 2H); 19F NMR (377 MHz, DMSO-d6) 6-118.73 (dt, J = 55.8, 15.7 Hz, 2F)
1115[Figure (not displayed)]
MS (ESI) m/z 683.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 2.7 Hz, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.82- 3.70 (m, 1H), 3.20-3.09 (m, 2H), 2.78-2.67 (m, 2H), 1.92-1.79 (m, 7H)
1116[Figure (not displayed)]
MS (ESI) m/z 677.1 [M + 1]+; 1H NMR (400 MHz, Chloroform-d) δ 9.16 (s, 1H), 8.78 (d, J = 4.9 Hz, 1H), 8.56 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.51 (dd, J = 8.4, 2.1 Hz, 1H), 7.46-7.41 (m, 2H), 4.81 (s, 2H), 3.66-3.38 (m, 5H), 3.01 I (t, J = 11.8 Hz, 2H), 2.50-2.31 (m, 5H), 2.13 (d, J = 14.0 Hz, 2H)
1117[Figure (not displayed)]
MS (ESI) m/z 683.3 [M + 1]+; 1H NMR (400 MHz, Chloroform-d) δ 9.12 (s, 1H), 8.78 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 7.48 (dd, J = 8.9, 2.6 Hz, 1H), 7.32-7.27 (m, 2H), 7.03 (d, J = 8.9 Hz, 1H), 4.41 (t, J = 4.9 Hz, 2H), 4.29 (t, J = 4.9 Hz, 2H), 3.64-3.48 (m, 6H), 3.13-3.01 (m, 2H), 2.46-2.32 (m, 2H), 1.89 (s, 3H)
1118[Figure (not displayed)]
MS (ESI) m/z 694.3 [M + 1]+; 1H NMR (400 MHz, Chloroform-d) δ 8.75 (s, 1H), 8.71 (d, J = 4.8 Hz, 1H), 8.49 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.52 (dd, J = 8.4, 2.1 Hz, 1H), 7.40 (d, J = 2.1 Hz, 1H), 7.38 (d, J = 4.9 Hz, 1H), 5.36 (d, J = 7.0 Hz, 2H), 4.77-4.64 (m, 3H), 4.34 (d, J = 7.0 Hz, 2H), 3.37 (d, J = 11.5 Hz, 2H), 3.28 (t, J = 12.1 Hz, 2H), 3.19 (s, 3H), 2.84-2.70 (m, 2H), 2.44 (s, 3H), 2.34 (d, J = 13.5 Hz, 2H), 1.85 (s, 3H)
1119[Figure (not displayed)]
MS (ESI) m/z 756.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.66 (s, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.35-4.24 (m, 1H), 3.38- 3.22 (m, 2H), 3.12-3.00 (m, 5H), 2.63-2.52 (m, 2H), 2.06 (s, 3H), 2.00-1.86 (m, 2H), 1.85- 1.75 (m, 2H)
1120[Figure (not displayed)]
MS (ESI) m/z 623.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80-8.58 (m, 3H), 7.78- 7.63 (m, 3H), 7.53 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.27 (t, J = 11.8 Hz, 1H), 3.09 (s, 3H), 2.04 (s, 3H), 1.89-1.75 (m, 4H), 1.71-1.56 (m, 3H), 1.38 (q, J = 12.8, 12.2 Hz, 2H), 1.16 (q, J = 13.1 Hz, 1H)
1121[Figure (not displayed)]
LCMS (ESI) m/z 677.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.44 (s, 1H), 7.42 4.41 (t, J = 4.9 Hz, 2H), 4.33-4.09 (m, 4H), 2.08 (d, J = 4.4 Hz, 3H), 1.80 (s, 3H)
1122[Figure (not displayed)]
LCMS (ESI) m/z 631.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.37 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 2H), 7.05 (dt, J = 14.5, 6.8 Hz, 1H), 5.46 (d, J = 57.5 Hz, 1H), 4.56 (s, 2H), 4.46-4.32 (m, 4H), 4.26 (t, J = 5.0 Hz, 4H), 1.79 (s, 3H)
1123[Figure (not displayed)]
LCMS (ESI) m/z 627.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.38 (s, 1H), 7.67-7.58 (m, 2H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.1 Hz, 1H), 7.04 (d, J = 15.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.0 Hz, 2H), 2.98 (s, 6H), 1.86 (s, 3H), 1.53 (s, 2H), 1.35 (s, 2H)
1124[Figure (not displayed)]
LCMS (ESI) m/z 677.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.84 (dd, J = 4.8, 1.4 Hz, 1H), 8.38 (d, J = 2.2 Hz, 1H), 7.60 (ddd, J = 9.0, 2.7, 0.8 Hz, 1H), 7.50 (s, 1H), 7.51-7.41 (m, 1H), 7.35 (d, J = 9.0 Hz, 1H), 7.11 (d, J = 15.4 Hz, 1H), 6.93 (d, J = 15.4 Hz, 1H), 6.06 (tt, J = 56.0, 4.2 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.24 (t, J = 4.9 Hz, 2H), 3.19 (td, J = 15.5, 4.2 Hz, 2H), 2.61 (s, 3H), 1.73 (d, J = 1.3 Hz, 3H), 1.16-1.13 (m, 2H), 1.12-1.01 (m, 2H)
1125[Figure (not displayed)]
LCMS (ESI) m/z 728.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78-8.71 (m, 2H), 8.64 (s, 1H), 7.75 (dd, J = 7.9, 1.0 Hz, 1H), 7.71-7.64 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 2.09 (s, 3H), 0.70 (s, 2H), 0.65 (s, 2H)
1126[Figure (not displayed)]
LCMS (ESI) m/z 734.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.58 (s, 1H), 8.38 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.47-7.37 (m, 2H), 7.33 (d, J = 9.0 Hz, 1H), 4.49 (bs, 1H), 4.36 (t, J = 4.9 Hz, 2H), 4.18 (t, J = 4.9 Hz, 2H), 2.99 (s, 3 H), 1.73 (s, 3H), 1.51 (ddd, J = 13.2, 8.1, 4.9 Hz, 1H), 0.71- 0.60 (m, 4H)
1127[Figure (not displayed)]
LCMS (ESI) m/z 714.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.54 (s, 1H), 8.34 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 7.39-7.29 (m, 2H), 4.51 (s, 1H), 4.46-4.30 (m, 4H), 4.19 (t, J = 5.1 Hz, 2H), 3.50 (d, J = 11.8 Hz, 2H), 3.26-3.11 (m, 2H), 3.08 (s, 3H), 2.75-2.66 (m, 1H), 2.25 (d, J = 12.7 Hz, 2H), 2.03 (d, J = 12.8 Hz, 2H), 1.79 (s, 3H), 1.07 (d, J = 6.9 Hz, 6H)
1128[Figure (not displayed)]
LCMS (ESI) m/z 712.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.53 (s, 1H), 8.33 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (d, J = 4.9 Hz, 1H), 7.38-7.30 (m, 2H), 4.58-4.43 (m, 3H), 4.36 (t, J = 5.1 Hz, 2H), 4.19 (t, J = 5.0 Hz, 2H), 3.52 (d, J = 11.8 Hz, 3H), 3.18 (t, J = 12.7 Hz, 2H), 3.07 (s, 3H), 2.24 (d, J = 12.7 Hz, 2H), 2.17-1.95 (m, 3H), 1.80 (s, 3H), 1.06 (dd, J = 23.8, 2.3 Hz, 4H)
1129[Figure (not displayed)]
LCMS (ESI) m/z 730.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81-8.71 (m, 2H), 8.65 (s, 1H), 7.76 (dd, J = 7.9, 1.0 Hz, 1H), 7.72-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 3.11 (s, 3H), 2.40-2.18 (m, 2H), 2.11 (s, 4H), 1.03 (d, J = 6.9 Hz, 6H)
1130[Figure (not displayed)]
LCMS (ESI) m/z 469.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.69 (m, 4H), 8.62 (s, 2H), 7.76-7.61 (m, 7H), 7.52 (d, J = 4.8 Hz, 2H), 4.79 (s, 5H), 4.51 (s, 1H), 3.71 (s, 1H), 3.34 (s, 1H), 2.07 (s, 8H), 2.01 (s, 1H), 1.22 (s, 14H)
1131[Figure (not displayed)]
LCMS (ESI) m/z 744.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.68 (d, J = 14.8 Hz, 2H), 7.76 (d, J = 9.0 Hz, 1H), 7.73-7.66 (m, 2H), 7.55 (d, J = 4.7 Hz, 1H), 4.82 (s, 2H), 4.21 (d, J = 6.9 Hz, 1H), 3.75 (s, 1H), 3.07 (s, 3H), 3.00 (s, 2H), 2.05 (s, 3H), 1.77 (s, 4H), 0.85 (s, 4H)
1132[Figure (not displayed)]
LCMS (ESI) m/z 718.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.61 (s, 1H), 7.72 (d, J = 8.9 Hz, 1H), 7.68-7.63 (m, 2H), 7.51 (d, J = 4.8 Hz, 1H), 4.79 (s, 2H), 4.50 (s, 1H), 3.71 (t, J = 13.7 Hz, 7H), 3.08 (s, 3H), 2.22 (s, 2H), 2.06 (s, 3H), 2.03-1.91 (m, 2H)
1133[Figure (not displayed)]
LCMS (ESI) m/z 732.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79-8.71 (m, 2H), 8.65 (s, 1H), 7.79-7.72 (m, 1H), 7.72-7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.76 (s, 2H), 3.11 (s, 3H), 2.08 (s, 3H)
1134[Figure (not displayed)]
LCMS (ESI) m/z 720.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.68 (m, 2H), 8.62 (s, 1H), 7.76-7.69 (m, 1H), 7.69-7.62 (m, 2H), 7.52 (d, J = 4.8 Hz, 1H), 4.86-4.58 (m, 2H), 4.79 (s, 3H), 4.42 (s, 1H), 2.05 (s, 3H), 1.92 (bs, 3H)
1135[Figure (not displayed)]
LCMS (ESI) m/z 744.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 1.8 Hz, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.69 (d, J = 8.9 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.72 (t, J = 75.2 Hz, 1H), 4.83 (s, 2H), 4.78 (s, 1H), 4.56 (s, 1H), 3.94 (d, J = 8.4 Hz, 1H), 3.57 (d, J = 11.9 Hz, 2H), 3.12 (s, 3H), 3.06 (d, J = 10.5 Hz, 2H), 2.77-2.64 (m, 2H), 2.54 (s, 1H), 2.11 (s, 7H). 19F NMR (377 MHz, DMSO-d6) 6- 73.82-82.25 (d, J = 75.1 Hz)
1136[Figure (not displayed)]
LCMS: 1.77 Min, 700.2. [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 610.73 (s, 1H), 8.78-8.72 (m, 2H), 8.64 (s, 1H), 7.81-7.73 (m, 1H), 7.72 J = 53.2 Hz, 1H), 4.82 (s, 2H), 4.12 (s, 4H), 3.92 (t, J = 16.0 Hz, 2H), 3.64 (d, J = 31.4 Hz, 4H), 2.06 (s, 3H)
1137[Figure (not displayed)]
LCMS: 1.71 Min, 714.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.81-8.72 (m, 2H), 8.64 (s, 1H), 7.79-7.72 (m, 1H), 7.71 (s, 2H), 4.32-3.89 (m, 6H), 3.64 (m, 4H), 2.07 (d, J = 1.6 Hz, 6H), 2.00 (s, 3H), 1.74 (t, J = 19.6 Hz, 3H)
1139[Figure (not displayed)]
MS (ESI) m/z 708.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.39 (t, J = 5.0 Hz, 2H), 4.21 (t, J = 5.0 Hz, 2H), 3.75- 3.30 (m, 10H), 3.09 (s, 3H), 1.75 (s, 6H)
1140[Figure (not displayed)]
MS (ESI) m/z 706.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.69 (d, J = 22.6 Hz, 2H), 7.76 (d, J = 9.0 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.31 (s, 1H), 3.34 (s, 1H), 3.10 (s, 5H), 2.61 (s, 2H), 2.06 (s, 3H), 1.96 (q, J = 11.8 Hz, 2H), 1.82 (d, J = 12.1 Hz, 2H)
1141[Figure (not displayed)]
MS (ESI) m/z 702.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.78-7.74 (m, 1H), 7.71-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 3.11 (s, 3H), 2.09 (s, 3H), 1.78 (t, J = 19.5 Hz, 3H)
1142[Figure (not displayed)]
MS (ESI) m/z 698.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78-8.73 (m, 2H), 8.65 (s, 1H), 7.76 (dd, J = 8.1, 0.8 Hz, 1H), 7.72-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.57 (d, J = 12.1 Hz, 1H), 3.67 (d, J = 12.6 Hz, 2H), 3.48 (dd, J = 22.6, 5.0 Hz, 2H), 3.33 (d, J = 11.5 Hz, 1H), 3.12 (s, 3H), 2.40-2.26 (m, 2H), 2.15-1.98 (m, 5H), 1.50 (d, J = 21.4 Hz, 6H)
1143[Figure (not displayed)]
MS (ESI) m/z 842.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 1H NMR (400 MHz, DMSO- d6) 613.21 (bs, 1H), 9.97 (s, 1H), 8.97-8.93 (m, 2H), 8.85 (d, J = 4.9 Hz, 1H), 8.69 (s, 1H), 8.50 (s, 1H), 8.10-8.05 (m, 2H), 7.77 (dd, J = 8.4, 0.5 Hz, 1H), 7.70 (dd, J = 8.4, 2.2 Hz, 1H), 7.66 (dd, J = 2.2, 0.5 Hz, 1H), 7.64 (dd, J = 4.9, 0.4 Hz, 1H), 4.82 (s, 2H), 4.57 (s, 1H), 3.96- 3.26 (m, 4H), 3.11 (s, 3H), 2.26 (s, 2H), 2.04 (dd, J = 20.6, 10.2 Hz, 2H), 1.92 (s, 3H), 1.78 (t, J = 19.5 Hz, 3H)
1144[Figure (not displayed)]
MS (ESI) m/z 842.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 9.28 (d, J = 2.3 Hz, 1H), 8.92 (d, J = 4.6 Hz, 1H), 8.84 (d, J = 4.9 Hz, 1H), 8.67 (s, 1H), 8.56-8.51 (m, 1H), 8.48 (s, 1H), 7.73 (ddd, J = 16.1, 10.9, 8.4 Hz, 3H), 7.66 (d, J = 2.2 Hz, 1H), 7.63 (d, J = 4.9 Hz, 1H), 4.81 (s, 2H), 3.11 (s, 3H), 1.90 (s, 3H)
1145[Figure (not displayed)]
MS (ESI) m/z 630.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 8.69 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (s, 1H), 7.40 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.1 Hz, 2H), 4.31 (d, J = 14.2 Hz, 2H), 4.24 (t, J = 5.1 Hz, 2H), 3.61 (d, J = 12.0 Hz, 2H), 3.45 (t, J = 13.1 Hz, 2H), 3.24 (q, J = 10.2 Hz, 2H), 2.91 (d, J = 3.4 Hz, 3H), 2.72 (s, 3H), 1.90 (s, 3H)
1146[Figure (not displayed)]
MS (ESI) m/z 842.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 1H NMR (400 MHz, DMSO- d6) δ 13.03 (s, 1H), 8.90 (d, J = 4.9 Hz, 1H), 8.72 (ddd, J = 4.6, 1.7, 0.9 Hz, 1H), 8.65 (s, 1H), 8.60 (s, 1H), 8.30-8.25 (m, 1H), 8.21 (td, J = 7.7, 1.7 Hz, 1H), 7.80-7.72 (m, 2H), 7.72- 7.68 (m, 2H), 7.66 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 3.09 (s, 3H), 1.94 (s, 3H), 1.77 (t, J = 18.9 Hz, 2H)
1148[Figure (not displayed)]
MS (ESI) m/z 676.21. [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.22 (bs, 1H), 8.83 (d, J = 4.6 Hz, 1H), 8.49 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.87 (t, J = 7.4 Hz, 1H), 7.77 (m, 2H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.7 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.44 (s, 2H), 4.27 (s, 2H), 2.77 (s, 3H), 1.85 (s, 3H)
1149[Figure (not displayed)]
MS (ESI) m/z 631.26 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.60 (bs, 1H), 8.56 (s, 1H), 7.58 (dd, J = 8.8, 2.4 Hz, 1H), 7.40-7.35 (m, 3H), 5.02 (bs, 1H), 4.39 (s, 2H), 4.19 (s, 2H), 3.90-3.82 (m, 2H), 3.74 (t, J = 8.0 Hz, 1H), 3.54 (d, J = 11.6 Hz 1H), 2.70 (s, 3H), 2.59 (s, 3H), 2.05-1.85 (m, 2H), 1.84 (s, 3H)
1152[Figure (not displayed)]
MS (ESI) m/z 616.24 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.56 (bs, 1H), 9.01 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 2.8, 9.2 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.39 (s 1H), 7.34 (d, J = 8.8 Hz, 1H), 4.38 (s, 2H) 4.24 (s, 2H), 4.0-3.9 (m, 1H), 3.67-3.61 (m, 1H), 3.19 (s, 3H), 2.69 (bs, 5H), 2.35-2.31 (m, 2H), 1.86 (s, 3H)
1157[Figure (not displayed)]
MS (ESI) m/z 789.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.66 (s, 1H), 8.87 (d, J = 4.8 Hz, 1H), 8.60 (m, 1H), 8.58 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.54 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.38 (d, J = 9.2 Hz, 1H), 4.39 (t, J = 6.0 Hz, 2H), 4.35-4.25 (m, 1H), 4.19 (t, J = 6.0 Hz, 2H), 3.58 (s, 3H), 3.40- 3.20 (m, 2H), 3.07 (s, 5H), 2.65-2.55 (m, 2H), 1.99-1.90 (m, 2H), 1.85-1.79 (m, 2H), 1.74 (s,
1160[Figure (not displayed)]
MS (ESI) m/z 692.45 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.83 (s, 1H), 8.75 (d, J = 4.6 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.69 (s, 1H), 7.66 (s, 1H), 7.52 (d, J = 4.5 Hz, 1H), 4.83 (s, 2H), 4.31 (bs, 1H), 3.43 (bs, 7H), 2.85 (s, 4H), 2.11 (s, 3H)
1161[Figure (not displayed)]
MS (ESI) m/z 708.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.76 (dd, J = 8.3, 0.5 Hz, 1H), 7.71-7.65 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.53 (s, 2H), 4.06-2.83 (m, 8H), 2.13 (s, 3H)
1162[Figure (not displayed)]
MS (ESI) m/z 636.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.18 (bs, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.38 (m, 2H), 3.79 (m, 2H,), 3.49 (m, 4H), 3.03 (m, 1H), 2.14 (s, 3H), 0.93 (m, 4H)
1163[Figure (not displayed)]
MS (ESI) m/z 686.0 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 8.83 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 1H), 7.53 (d, J = 4.8 Hz, 1H), 4.72 (s, 2H), 3.80 (bs, 4H), 3.39 (bs, 4H), 3.05-3.02 (m, 5H), 2.16 (s, 3H)
1164[Figure (not displayed)]
MS (ESI) m/z 694.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.72- 4.54 (m, 2H), 4.39 (bs, 2H), 4.22 (bs, 2H), 3.25- 2.78 (m, 10H), 1.81 (s, 3H), 1.45 (bs, 3H)
1165[Figure (not displayed)]
MS (ESI) m/z, 714.50 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 9.80 (bs, 1H), 8.76 (s, 1H), 8.75 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.56 (bs, 1H), 3.56 (bs, 4H), 3.11 (bs, 1H), 3.06 (s, 3H), 3.05 (bs, 4H), 2.13 (bs, 4H), 2.11 (s, 3H)
1166[Figure (not displayed)]
MS (ESI) m/z 714.58 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76-8.74 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.58-4.38 (m, 2H), 3.11 (s, 3H), 2.90-2.88 (m, 2H), 2.50-2.32 (m, 4H), 2.20-2.15 (m, 5H), 2.12-2.10 (m, 2H)
1167[Figure (not displayed)]
MS (ESI) m/z 668.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 10.22 (bs, 1H), 8.85 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69-7.66 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.39 (d, J = 11.6 Hz, 2H), 3.76 (bs, 6H), 3.43 (bs, 2H), 2.14 (s, 3H), 1.29 (d, J = 18.8 Hz, 2H), 0.99 (d, J = 7.6 Hz, 2H)
1168[Figure (not displayed)]
MS (ESI) m/z 722.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.52 (bs, 1H), 4.39 (s, 2H), 4.21 (s, 2H), 3.90-3.82 (m, 1H), 3.36-3.31 (m, 6H), 3.09 (s, 3H), 2.33- 2.27 (m, 1H), 2.02-2.07 (m, 4H), 1.79 (s, 3H), 0.99 (t, J = 7.2 Hz, 3H)
1169[Figure (not displayed)]
MS (ESI) m/z 696.24 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76-8.75 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.54 (s, 1H), 3.74-3.72 (m, 4H), 3.31-3.29 (m, 2H), 3.12 (s, 3H), 2.28-2.22 (m, 2H), 2.13-2.10 (m, 5H), 1.25 (d, J = 19.6 Hz, 2H), 0.96 (d, J = 8.0 Hz, 2H)
1170[Figure (not displayed)]
MS (ESI) m/z 736.43 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76-.8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.56-4.52 (m, 3H), 3.67-3.55 (m, 4H), 3.25-3.19 (m, 2H), 3.11 (s, 3H), 2.23-2.20 (m, 2H), 2.17- 2.10 (m, 5H)
1171[Figure (not displayed)]
MS (ESI) m/z 664.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 6.0 Hz, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.60-4.59 (m, 1H), 3.66 (d, J = 11.6 Hz, 2H), 3.43-3.22 (m, 2H), 3.09 (s, 3H), 2.85 (bs, 1H), 2.10 (s, 7H), 0.95-0.85 (m, 4H)
1172[Figure (not displayed)]
MS (ESI) m/z 744.02 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.89-6.52 (m, 1H), 4.82 (s, 2H), 4.58-4.45 (m, 2H), 3.48-3.38 (m, 5H), 3.10 (s, 3H), 3.08-3.06 (m, 2H), 2.40.2.38 (m, 2H), 2.20-2.10 (m, 5H)
1173a[Figure (not displayed)]
MS (ESI) m/z 762.47 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.77-8.75 (m, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.56 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.73 (quin, J = 7.2 Hz, 1H), 4.59 (bs, 1H), 3.62 (bs, 4H), 3.41 (bs, 1H), 3.12 (bs, 5H), 2.89 (bs, 2H), 2.11 (bs, 7H)
1173b[Figure (not displayed)]
MS (ESI) m/z 671.41 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.68 (d, J = 1.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 3H), 3.38-3.28 (m, 4H), 3.11 (s, 9H), 2.02 (s, 3H), 1.97-1.91 (m, 2H), 1.89-1.83 (m, 2H)
1174[Figure (not displayed)]
MS (ESI) m/z 710.42 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 9.40 (bs, 1H), 8.76-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.56-4.53 (m, 1H), 3.94-3.80 (m, 4H), 3.66-3.59 (m, 4H), 3.11 (s, 3H), 2.40-2.34 (m, 3H), 2.27-2.24 (m, 1H), 2.10-2.01 (m, 5H), 1.91-1.88(m, 1H), 1.70-1.63(m, 1H)
1175[Figure (not displayed)]
MS (ESI) m/z 732.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77-8.74 (m, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 1.6 Hz, 1H), 7.68 (s, 1H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.48 (bs, 1H), 3.65 (m, 4H), 3.10 (s, 3H), 2.50-2.39 (m, 2H), 2.09 (s, 3H), 2.04 (bs, 4H), 1.44-1.33 (m, 2H)
1176[Figure (not displayed)]
MS (ESI) m/z 720.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.4 Hz, 1H), 8.74 (s, 1H), 8.67 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.69-7.67 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.18-4.15 (m, 1H), 3.67-3.64 (m, 2H), 3.29 (bs, 2H), 3.07 (d, J = 9.2 Hz, 2H), 2.60-2.55 (m, 2H), 2.06 (s, 3H), 1.96-1.94 (m, 2H), 1.85-1.82 (m, 2H), 1.11 (t, J = 6.8 Hz, 3H)
1177[Figure (not displayed)]
MS (ESI) m/z 716.60 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.14 (bs, 1H), 8.77 (d, J = 4.4 Hz, 2H), 8.66 (s, 1H), 7.77-7.74 (m, 1H), 7.69-7.68 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.39 (bs, 1H), 3.63 (bs, 4H), 3.30 (bs, 4H), 2.34 (bs, 2H), 2.08 (s, 5H), 1.75 (t, J = 18.0 Hz, 3H), 1.13 (t, J = 6.8 Hz, 3H)
1180[Figure (not displayed)]
MS (ESI) m/z 713.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.62 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.68 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.41-4.39 (d, J = 12.8 Hz, 2H), 3.83-3.69 (m, 4H), 3.23-3.14 (m, 4H), 2.43 (m, 2H), 2.33-2.25 (m, 3H), 2.10 (s, 3H), 1.91-1.88 (m, 2H)
1181[Figure (not displayed)]
MS (ESI) m/z 696.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.74 (bs, 1H), 8.78-8.72 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.70-7.62 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 5.35-5.18 (m, 1H), 4.82 (s, 2H), 4.60-4.52 (m, 1H), 4.04-3.98 (m, 1H), 3.60-3.50 (m, 2H), 3.15-2.95 (m, 5H), 2.80-2.45 (m, 4H), 2.20-2.00 (m, 7H)
1182[Figure (not displayed)]
MS (ESI) m/z 730.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz 1H), 8.71 (s, 1H), 8.65 (s, 1H), 7.76-7.74 (m, 1H), 7.69-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.46 (t, J = 54.4 Hz, 1H), 4.81 (s, 2H), 4.50 (d, J = 6.8 Hz, 2H), 4.44 (d, J = 6.4 Hz, 2H), 4.32- 4.28 (m, 1H), 3.16 (s, 3H), 2.91-2.89 (m, 2H), 2.59-2.53 (m, 2H), 2.05 (s, 3H), 1.89-1.86 (m, 4H)
1183[Figure (not displayed)]
MS (ESI) m/z 821.52 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.75 (d, J = 2.4 Hz, 2H), 7.77 (d, J = 8.8 Hz, 1H), 7.71-7.68 (m, 2H), 7.62 (d, J = 4.8 Hz, 1H), 5.21 (quin, J = 7.6 Hz, 1H), 4.97- 4.90 (m, 4H), 4.82 (s, 2H), 4.59 (m, 1H), 3.69- 3.49 (m, 4H), 3.11 (bs, 5H), 2.32 (m, 2H), 1.98 (m, 2H), 1.93 (s, 3H), 1.76 (t, J = 19.6 Hz, 3H)
1184[Figure (not displayed)]
MS (ESI) m/z 728.48 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) 613.11 (bs, 1H), 8.78-8.76 (m, 2H), 8.65 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.70-7.68 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.37 (bs, 1H), 3.75- 3.59 (m, 5H), 3.05 (bs, 6H), 2.15 (bs, 4H), 2.10 (s, 3H), 1.16 (t, J = 6.4 Hz, 3H)
1185[Figure (not displayed)]
MS (ESI) m/z 712.32 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.09 (bs, 1H), 8.76-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82-4.75 (m, 6H), 4.55 (bs, 1H), 3.91-3.85 (m, 2H), 3.52-3.35 (m, 4H), 3.10 (s, 3H), 2.32-2.21 (m, 2H), 2.09 (bs, 5H)
1186[Figure (not displayed)]
MS (ESI) m/z 694.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 2.8 Hz, 1H), 8.76 (s, 1H), 8.65 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.69 (d, J = 6.8 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.75 (bs, 4H), 4.38 (bs, 2H), 3.61 (d, J = 6.8 Hz, 2H), 3.52 (bs, 2H), 3.16 (bs, 2H), 2.16-2.10 (m, 7H), 1.15 (t, J = 6.8 Hz, 3H)
1187[Figure (not displayed)]
MS (ESI) m/z 715.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 8.63 (s, 1H), 7.75 (d, J = 8.8, 1H), 7.68-7.68 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 6.69 (t, J = 75.2 Hz, 1H), 4.81 (s, 2H), 4.70 (t, J = 5.6 Hz, 1H), 4.04 (d, J = 13.2 Hz, 2H), 3.60 (t, J = 6.4 Hz, 2H), 3.32-3.27 (m, 2H), 3.00 (t, J = 6.8 Hz, 2H), 2.37 (bs, 1H), 2.05 (s, 3H), 1.80 (d, J = 10.4 Hz, 2H), 1.39-1.32 (m, 2H)
1188[Figure (not displayed)]
MS (ESI) m/z 791.62 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.81-8.78 (m, 3H), 7.77 (d, J = 8.40 Hz, 1H), 7.71-7.67 (m, 2H), 7.62 (d, J = 4.80 Hz, 1H), 4.83 (s, 2H), 4.59 (bs, 1H), 3.74-3.54 (m, 6H), 3.08 (s, 3H), 2.98-2.88 (m, 6H), 2.11-2.05 (m, 4H), 2.00 (s, 3H)
1189[Figure (not displayed)]
MS (ESI) m/z 758.56 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.74 (m, 2H), 8.64 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.65 (t, J = 74.4 Hz, 1H), 4.82 (s, 2H), 4.57-4.47 (m, 2H), 3.53 (d, J = 11.6 Hz, 2H), 3.23-3.10 (m, 7H), 2.54- 2.49 (m, 2H), 2.32-2.28 (m, 1H), 2.16-2.09 (m, 7H), 2.06-1.91 (m, 2H)
1190[Figure (not displayed)]
MS (ESI) m/z 716.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.09 (bs, 1H), 9.32 (bs, 1H), 8.76-8.74 (m, J = 7.8 Hz, 2H), 8.64 (s, 1H) 7.75 (d, J = 8.2 Hz, 1H), 7.71-7.65 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.60-4.50 (m, 1H), 3.69 (d, J = 10.4 Hz, 2H), 3.30-311 (m, 4H), 3.10 (s, 3H), 2.50-2.32 (merged, 2H), 2.20-2.05 (m, 7H), 1.70 (t, J = 19.2 Hz, 3H)
1191[Figure (not displayed)]
MS (ESI) m/z 752.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.77-8.741 (m, 2H), 8.66 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.68 (d, J = 6.0 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.57 (t, J = 52.0 Hz, 1H), 4.81 (s, 2H), 4.29 (bs, 1H), 3.64 (d, J = 6.8 Hz, 2H), 3.03 (bs, 4H), 2.50 (s, 2H), 2.06 (s, 3H), 1.98-1.84 (m, 4H), 1.13-1.08 (m, 3H)
1194[Figure (not displayed)]
MS (ESI) m/z 602.22 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 1H), 9.01 (s, 1H), 8.41 (s, 1H), 7.62-7.57 (m, 2H), 7.41 (d, J = 2.4 Hz, 1H), 7.39 (s, 1H), 7.34 (d, J = 8.0 Hz, 1H), 4.38 (s, 2H), 4.24 (s, 2H), 4.19-4.15 (m, 1H), 3.56 (bs, 1H), 2.68-2.62 (m, 5H), 2.32- 2.27 (m, 2H), 1.84 (s, 3H)
1195[Figure (not displayed)]
MS (ESI) m/z 720.41 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.56 Hz, 1H), 8.68 (s, 1H), 8.59 (s, 1H), 7.74 (d, J = 8.12 Hz, 1H), 7.67-7.64 (m, 2H), 7.43 (d, J = 4.64 Hz, 1H), 4.80 (s, 2H), 4.29-4.23 (m, 1H), 3.83 (s, 3H), 3.21 (q, J = 10.08 Hz, 2H), 3.10 (s, 3H), 3.04 (d, J = 11.4 Hz, 2H), 2.54 (bs, 2H), 2.03 (s, 3H), 1.98-1.89 (m, 2H), 1.78 (d, J = 10.52 Hz, 2H)
1196[Figure (not displayed)]
MS (ESI) m/z 644.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.39 (bs, 1H), 8.62 (s, 1H), 7.59 (dd, J = 2.48, 8.88 Hz ,1H), 7.40-7.38 (m, 2H), 7.35 (d, J = 8.92 Hz, 1H), 4.63-4.59 (m, 2H), 4.47 (bs, 2H), 4.39 (t, J = 4.64 Hz, 2H), 4.23 (t, J = 4.64 Hz, 3H), 2.82 (bs, 6H), 2.70 (s, 3H), 2.54 (s, 3H), 1.94 (s, 3H)
1198[Figure (not displayed)]
MS (ESI) m/z 620.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.63 (bs, 1H) 8.55 (s, 1H), 7.59 (dd, J = 8.88, 2.62 Hz, 1H), 7.42 (t, J = 6.0 Hz, 2H), 7.35 (d, J = 8.8 Hz, 1H), 4.40 (d, J = 4.4 Hz, 2H), 4.26 (s, 2H), 4.26 (t, J = 4.8 Hz, 2H), 2.98- 3.04 (m, 2H), 2.55 (d, J = 4.0 Hz, 1H), 1.93 (s, 3H), 1.13-1.36 (m, 7H)
1199[Figure (not displayed)]
MS (ESI) m/z 629.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.69 (bs, 1H), 8.49 (s, 1H), 7.59 (dd, J = 8.88, 2.62 Hz, 1H), 7.36- 7.43 (m, 3H), 4.41 (t, J = 6.0 Hz, 2H), 4.20 (t, J = 6.0 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 3.34 (s, 6H), 2.96- 3.01 (m, 2H), 2.40 (d, J = 4.0 Hz, 1H), 1.81 (s, 3H), 1.31 (t, J = 12.8 Hz, 3H), 1.03- 1.12 (m, 4H)
1202[Figure (not displayed)]
MS (ESI) m/z 656.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 14.39 (bs, 1H), 10.23 (bs, 1H), 8.68 (s, 1H), 7.59 (d, J = 8.0, 2.4 Hz, 1H), 7.45-7.38 (m, 2H), 7.39 (d, J = 8.8 Hz, 1H), 4.87 (d, J = 4.8 Hz, 2H), 4.39 (bs, 2H), 4.23 (bs, 2H), 3.91-3.82 (m, 2H), 3.60-3.49 (m, 2H), 3.00-2.88 (m, 2H), 2.75 (s, 3H), 2.70 (s, 3H), 2.53 (s, 3H), 1.86 (s, 3H)
1203[Figure (not displayed)]
MS (ESI) m/z 656.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 14.39 (bs, 1H), 10.23 (bs, 1H), 8.68 (s, 1H), 7.59 (d, J = 8.0, 2.4 Hz, 1H), 7.45-7.38 (m, 2H), 7.39 (d, J = 8.8 Hz, 1H), 4.87 (d, J = 4.8 Hz, 2H), 4.39 (bs, 2H), 4.23 (bs, 2H), 3.91-3.82 (m, 2H), 3.60-3.49 (m, 2H), 3.00-2.88 (m, 2H), 2.75 (s, 3H), 2.70 (s, 3H), 2.53 (s, 3H), 1.86 (s, 3H)
1204[Figure (not displayed)]
MS (ESI) m/z 554.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.99 (s, 1H), 7.37 (s, 1H), 7.31-7.28 (m, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.14 (d, J = 9.2 Hz, 1H), 6.92 (s, 1H), 6.38 (bs 1H), 4.33 (bs, 2H), 4.30 (bs, 2H), 3.80 (s, 2H), 2.60 (t, J = 3.6 Hz, 1H), 2.18 (s, 3H), 1.21 (d, J = 7.6 Hz, 2H), 1.12 (bs, 2H)
1216[Figure (not displayed)]
MS (ESI) m/z 641.37 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.75 (bs, 1H), 8.84 (s, 1H), 8.31 (s, 1H), 7.60 (dd, J = 2.52, 8.88 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 2.48 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.39 (t, J = 4.40 Hz, 2H), 4.26 (t, J = 4.44 Hz, 2H), 3.84 (bs, 2H), 3.52 (bs, 2H), 3.31 (s, 3H), 3.01 (q, J = 7.48 Hz, 2H), 2.97 (bs, 1H), 2.91 (bs, 2H), 1.97 (s, 3H), 1.36 (t, J = 7.56 Hz, 3H)
1217[Figure (not displayed)]
MS (ESI) m/z 706.31 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.43 (bs, 1H), 8.59 (s, 1H), 8.16 (d, J = 3.6 Hz, 2H), 7.59 (dd, J = 2.0, 7.2 Hz, 1H), 7.54 (bs, 3H), 7.41 (bs, 3H), 4.45 (bs, 4H), 4.27 (bs, 2H), 3.60 (bs, 2H), 3.48 (bs, 2H), 3.33 (bs, 2H), 2.90 (s, 3H), 2.66 (bs, 3H), 2.008 (s, 3H)
1219[Figure (not displayed)]
MS (ESI) m/z 656.26 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.41 (s, 1H), 7.58 (dd, J = 2.48, 8.92 Hz, 1H), 7.42 (m, 2H), 7.35 (d, J = 8.9 Hz, 1H), 4.39-4.37 (m, 2H), 4.20-4.19 (m, 2H), 3.36-3.33 (m, 1H), 3.13-3.07 (m, 1H), 3.01 (q, J 7.5 Hz, 2H), 2.75-2.72 (m, 2H), 2.32 (s, 3 H), 2.20-2.15 (m, 1H), 1.75 (s, 3H), 1.34 (t, J = 7.5 Hz, 3H), 0.70-0.65 (m, 2H), 0.55-0.70 (m, 2H)
1220[Figure (not displayed)]
MS (ESI) m/z 642.25 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.76 (bs, 1H), 9.42 (bs, 2H), 8.62 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (s, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.44-4.40 (m, 3H), 4.22 (s, 2H), 3.51-3.38 (m, 1H), 3.41- 319 (m, 2H), 3.04 (m, 3H), 1.83 (s, 3H), 1.36 (m, 4H), 0.84 (m, 1H)
1227[Figure (not displayed)]
MS (ESI) m/z 638.14 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.56 (bs, 1H), 9.65 (bs, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 2H), 7.36-7.32 (m, 2H), 7.28-7.23 (m, 2H), 4.41 (bs, 2H), 4.26 (bs, 2H), 2.70 (s, 3H), 2.16 (s, 3H), 1.38 (s, 3H)
1229[Figure (not displayed)]
MS (ESI) m/z 698.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.59 (bs, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.70-7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.90-4.79 (m, 4H), 4.40-4.29 (m, 1H), 3.65-3.35 (m, 3H), 3.09 (s, 3H), 2.85-2.80 (m, 3H), 2.18-1.65 (m, 11H)
1231[Figure (not displayed)]
MS (ESI) m/z 592.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79-8.77 (m, 2H), 8.15 (s, 1H), 7.57 (dd, J = 2.60, 8.84 Hz, 1H), 7.34-7.32 (m, 3H), 4.38 (t, J = 4.60 Hz, 2H), 4.26 (t, J = 4.56 Hz, 2H), 1.77 (s, 3H), 1.63 (s, 9H)
1232[Figure (not displayed)]
MS (ESI) m/z 615.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.34 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.47 (s, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.40-3.79 (m, 10H), 3.05-3.00 (m, 2H), 2.95 (s, 3H). 1.83 (s, 3H), 1.38-1.34 (t, J = 7.6 Hz, 3H)
1233[Figure (not displayed)]
MS (ESI) m/z 586.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.68 (d, J = 4.80 Hz, 1H), 8.51 (s, 1H), 7.74 (d, J = 8.40 Hz, 1H), 7.67-7.63 (m, 3H), 7.40 (d, J = 4.80 Hz, 1H), 4.88 (s, 2H), 2.18 (s, 3H), 1.59 (s, 9H)
1234[Figure (not displayed)]
MS (ESI) m/z 631.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.49 (s, 1H), 7.59 (dd, J = 8.88, 2.50 Hz, 1H), 7.41 (d, J = 2.60 Hz, 1H), 7.40 (s, 1H), 7.35 (d, J = 8.96 Hz, 1H), 4.37 (t, J = 5.00 Hz, 2H), 4.19 (t, J = 5.00 Hz, 2H), 4.11 (bs, 1H), 3.92-3.70 (m, 4H), 3.29 (s, 3H), 2.70 (s, 3H), 2.11-2.04 (m, 2H), 1.81 (s, 3H)
1235[Figure (not displayed)]
MS (ESI) m/z 631.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.76 (s, 1H), 8.54 (s, 1H), 8.48 (s, 1H), 7.59 (dd, J = 8.8 Hz, 2.4 Hz, 1H) 7.43 (s, 2H), 7.35 (d, J = 8.8 Hz, 1H), 5.07 (d, J = 2.8 Hz, 1H), 4.41 (bs, 1H), 4.37-4.36 (m, 2H), 4.42 (m, 2H), 3.93-3.87 (m, 2H), 3.79-3.75 (m, 1H), 3.59 (d, J = 11.2 Hz, 1H), 3.01 (q, J = 7.6 Hz, 2H), 2.04-2.01 (m, 1H), 1.93 (bs, 1H), 1.75 (s, 3H),1.35 (t, J = 7.6 Hz, 3H)
1236[Figure (not displayed)]
MS (ESI) m/z 631.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.35 (bs, 1H), 8.53 (s, 1H), 7.58 (dd, J = 8.96, 2.36 Hz, 1H), 7.39-7.34 (m, 3H), 4.45-4.36 (m, 3H), 4.21 (t, J = 4.24 Hz, 2H), 3.92-3.86 (m, 2H), 3.78-3.68 (m, 2H), 3.56 (d, J = 12.04 Hz, 1H), 2.70 (s, 3H), 2.53 (s, 3H), 2.22-1.86 (m, 5H)
1257[Figure (not displayed)]
MS (ESI) m/z 572.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.65 (d, J = 4.8 Hz, 1H), 7.71 (d, J = 5.2 Hz, 1H), 7.55 (dd, J = 8.8, 2.8 Hz, 1H), 7.44 (d, J = 5.2 Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.21 (d, J = 4.4 Hz, 1H), 4.36-4.23 (m, 6H), 3.60 (d, J = 12.0 Hz, 2H), 3.41 (t, J = 11.6 Hz, 2H), 3.29-3.16 (m, 2H), 2.90 (s, 3H), 1.81 (s, 3H)
1258[Figure (not displayed)]
MS (ESI) m/z 559.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.65 (d, J = 3.8, 1H), 7.75 (d, J = 4.76, 1H), 7.55-7.53 (m, 1H), 7.47 (d, J = 5.0 Hz, 1H), 7.39 (s, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.21 (d, J = 3.6 Hz, 1H), 5.07 (s, 1H), 4.41 (s, 1H), 4.35 (t, J = 3.6 Hz, 2H), 4.19 (t, J = 5.6 Hz, 2H), 3.89 (t, J = 5.9 Hz, 2H), 3.77-3.73 (m, 1H), 3.58 (d, J = 11.4 Hz, 1H), 2.00-1.98 (m, 1H), 1.93 (bs, 1H), 1.74 (s, 3H)
1264[Figure (not displayed)]
MS (ESI) m/z 633.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.37 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.44 (s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 5.2 Hz, 2H), 4.27 (t, J = 4.0 Hz, 2H), 3.52 (bs, 6H), 3.77-3.25 (m, 2H), 2.92 ( d, J = 3.2 Hz, 3H), 1.82 (s, 3H)
1265[Figure (not displayed)]
MS (ESI) m/z 642.16 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 9.54 (s, 1H), 8.80 (d, J = 4.8 Hz,1H), 8.55 (s, 1H), 7.57 (dd, J = 2.4, 8.8 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.40-7.36 (m, 2H), 4.55 (s, 2H), 4.48 (d, J = 14 Hz, 4H), 4.40 (s, 2H), 4.22 (d, J = 14.4 Hz, 4H), 2.85 (d, J = 4 Hz, 3H), 2.60 (s, 3H), 1.86 (s, 3H)
1266[Figure (not displayed)]
MS (ESI) m/z 629.0 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (d, J = 4.8 Hz, 1H), 8.55 (s, 1H), 8.49 (bs, 2H), 7.57 (dd, J = 2.4, 8.8 Hz ,1H), 7.45 (d, J = 4.8 Hz, 1H), 7.40-7.36 (m, 2H), 4.52 (s, 4H), 4.39 (d, J = 4.8 Hz, 2H), 4.22 (d, J = 5.2 Hz, 6H), 2.60 (s, 3H), 1.85 (s, 3H)
1268[Figure (not displayed)]
MS (ESI) m/z 678.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.82 (bs, 1H), 8.74 (d, J = 4.8 Hz, 1H), 8.48 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.76 (s, 1H), 7.56 (dd, J = 8.8, 2.4 Hz, 1H), 7.41 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.9 Hz, 1H), 7.28 (d, J = 4.4 Hz, 1H), 7.10 (d, J = 8.8 Hz, 2H), 4.43-4.36 (m, 2H), 4.27-4.17 (m, 4H), 3.86 (s, 3H), 3.62-3.53 (m, 2H), 3.41-3.29 (m, 2H), 3.21-3.10 (m, 2H), 2.90 (s, 3H), 1.78 (s, 3H)
1273[Figure (not displayed)]
MS (ESI) m/z 624.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 8.76 (d, J = 4.80 Hz, 1H), 8.66 (s, 1H), 7.76-7.64 (m, 3H), 7.53 (d, J = 4.80 Hz, 1H), 4.82 (s, 2H), 4.38- 4.35 (m, 2H), 3.63-3.60 (m, 2H), 3.48-3.25 (m, 4H), 2.91 (s, 3H), 2.73 (s, 3H), 2.14 (s, 3H)
1274[Figure (not displayed)]
MS (ESI) m/z 680.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.72 Hz, 1H), 8.52 (s, 1H), 7.59 (dd, J = 8.88, 2.44 Hz, 1H), 7.44 (d, J = 4.68, 1H), 7.40 (d, J = 2.4 Hz, 1H), 7.36 (d J = 9.0 Hz, 1H), 6.35-6.05 (m, 1H), 4.40 (t, J = 4.48 Hz, 2H), 4.20 (t, J = 4.72 Hz, 2H), 3.64 (s, 4H), 2.87-2.878 (m, 2H), 2.71 (s, 4H), 2.63 (s, 3H), 1.78 (s, 3H)
1279[Figure (not displayed)]
MS (ESI) m/z 622.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.45-4.36 (m, 2H), 4.30-4.20 (m, 2H), 4.15-4.00 (m, 1H), 2.70-2.50 (m, 2H), 2.44-2.20 (m, 3H), 2.14-2.01 (m, 1H), 1.84 (s, 3H)
1281[Figure (not displayed)]
MS (ESI) m/z 687.47 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 10.05 (bs, 1H), 8.87 (d, J = 3.2 Hz, 1H), 8.74 (s, 1H), 8.72 (d, J = 4.8 Hz, 1H), 8.47 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 2.0 Hz, 2H), 7.66 (s, 1H), 7.49 (d, J = 4.4 Hz, 1H), 6.53 (tt, J = 5.2, 51.2 Hz, 1H), 4.82 (s, 2H), 4.49 (bs, 1H), 3.64 (bs, 4H), 3.38 (bs, 2H), 3.16 (s, 3H), 2.17 (bs, 2H), 2.04 (bs, 5H)
1282[Figure (not displayed)]
MS (ESI) m/z 630.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.09 (bs, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.39 (s, 2H), 4.21 (s, 2H), 3.64 (s, 4H), 2.55-2.35 (m, 7H), 2.23 (s, 3H), 1.83 (s, 3H)
1297[Figure (not displayed)]
MS (ESI) m/z 644.30 [M + 1]+; 1 H NMR (400 MHz, DMSO-d6) δ 13.46 (bs, 1H), 8.66 (d, J = 4.8 Hz, 1H), 7.55 (dd, J = 8.8, 2.4 Hz, 1H), 7.37-7.28 (m, 3H), 4.42-4.34 (m, 2H), 4.21 (s, 2H), 3.63 (bs, 4H), 2.64 (s, 3H), 2.49-2.35 (m, 7H), 2.22 (s, 3H), 1.84 (s, 3H)
1301[Figure (not displayed)]
MS (ESI) m/z 628.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.82 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.48- 4.40 (m, 3H), 4.29-4.19 (m, 2H), 3.45-3.19 (m, 3H), 3.10-2.89 (m, 5H), 1.80 (s, 3H), 1.48-1.27 (m, 2H)
1302[Figure (not displayed)]
MS (ESI) m/z 648.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.15 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.43 (s, 1H), 7.57 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41-7.36 (m, 2H), 4.95 (s, 1H), 4.84 (s, 1H), 4.39 (d, J = 4.4 Hz, 2H), 4.30 (d, J = 7.6 Hz, 2H), 4.23 (s, 2H), 3.83-3.59 (m, 4H), 3.53- 3.34 (m, 4H), 1.83 (s, 3H)
1303[Figure (not displayed)]
MS (ESI) m/z 666.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37-7.35 (m, 1H), 6.46 (t, J = 54.8 Hz, 1H), 4.41-4.38 (m, 2H), 4.28-4.22 (m, 2H), 3.87-3.83 (m, 4H), 3.38-3.32 (m, 2H), 3.24-3.11 (m, 4H), 1.80 (s, 3H)
1304[Figure (not displayed)]
MS (ESI) m/z 684.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 11.77 (bs, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 8.40 (s, 1H), 7.58 (dd, J = 9.2, 6.8 Hz, 1H), 7.45-7.40 (m, 2H), 7.34 (d, J = 8.8 Hz, 1H), 4.37 (s, 2H), 4.20 (s, 2H), 3.65 (s, 4H), 3.35-3.20 (m, 2H), 2.81 (s, 4H), 1.75 (s, 3H)
1305[Figure (not displayed)]
MS (ESI) m/z 666 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz , 1H), 8.70 (s, 1H), 8.43 (s, 1H), 7.61 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 6.73-6.46 (m, 1H), 4.39 (s, 2H), 4.34 (s, 1H), 4.23 (s, 2H), 4.18 (s, 1H), 3.56-3.15 (m, 5H), 2.83 (s, 3H), 1.82 (s, 3H)
1306[Figure (not displayed)]
MS (ESI) m/z 642.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.43 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.44 (s, 1H), 7.61 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.41-7.38 (m, 2H), 4.41-4.40 (m, 4H), 4.31 (t, J = 2.4 Hz, 2H), 3.47 (bs, 6H), 3.01 (bs, 1H), 1.85 (s, 3H), 1.00-0.88 (bs, 2H)
1307[Figure (not displayed)]
MS (ESI) m/z 692.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.31 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.43 (s, 1H), 7.59 (dd, J = 2.40, 8.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.39 (s, 2H), 4.22 (s, 2H), 3.76 (m, 4H), 3.19-2.93 (m, 8H), 2.32 (m, 1H), 1.80 (s, 3H)
1308[Figure (not displayed)]
MS (ESI) m/z 698.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.33 (bs, 1H), 8.82 (d, J = 4.76 Hz, 1H), 8.69 (s, 1H), 8.43 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.7 Hz, 1H), 7.41 (d, J = 2.5 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H) , 4.39 (t, J = 4.8 Hz, 2H), 4.22 (t, J = 4.4 Hz, 2H), 3.38 (bs, 8H), 2.82 (s, 4H), 1.81 (s, 3H)
1309[Figure (not displayed)]
MS (ESI) m/z 694.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.45 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 6.22 (m, 1H), 4.39 (s, 2H), 4.21 (s, 2H), 3.72 (m, 4H), 2.96 (s, 4H), 1.79 (s, 3H), 1.23 (s, 6H)
1310[Figure (not displayed)]
MS (ESI) m/z 692.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.48 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.49 (d, J = 4.80, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 6.04 (t, J = 55.6 Hz, 1H), 4.38 (s, 2H), 4.20 (s, 2H), 3.55 (s, 4H), 3.01 (s, 4H), 1.75 (s, 3H), 0.90-078 (m, 4H)
1311[Figure (not displayed)]
MS (ESI) m/z 678.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 8.45 (s, 1H) 7.60 (dd, J = 9.2 Hz, 2.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.39 (bs, 2H), 4.32 (d, J = 12.8 Hz, 2H), 4.22 (bs, 4H), 3.64 (bs, 1H), 3.38 (bs, 1H), 3.19 (bs, 2H), 2.93 (bs, 2H), 2.15 (bs, 1H), 1.759 (s, 3H)
1312[Figure (not displayed)]
MS (ESI) m/z 680.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.22 (bs, 1H), 8.82 (d, J = 4.8 Hz 1H), 8.66 (s, 1H), 8.44 (s, 1H), 7.598 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 6.25 (m, 1H), 4.38 (s, 2H), 4.21 (s, 2H), 3.64 (m, 4H), 2.97 (m, 4H), 2.63 (s, 1H), 1.77 (s, 3H), 1.16 (s, 3H)
1313[Figure (not displayed)]
MS (ESI) m/z 658.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.43 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.41-7.36 (m, 2H), 4.42-4.39 (m, 4H), 4.24 (s, 2H), 3.72 (d, J = 12 Hz, 2H), 3.51 (t, J = 12.4 Hz, 2H), 3.19 (d, J = 9.6 Hz, 2H), 1.86 (s, 3H), 1.39 (s, 9H)
1314[Figure (not displayed)]
MS (ESI) m/z 654.34 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.22 (bs, 1H), 8.82 (d, J = 4.7 Hz, 1H), 8.57 (s, 1H), 8.46 (s, 1H), 7.59 (dd, J = 8.8, 2.5 Hz, 1H), 7.45 (d, J = 4.7 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 4.41 (s, 4H), 4.36 (s, 2H), 4.18 (s, 2H), 3.49 (bs, 4H), 1.90 (bs, 1H), 1.73 (s, 3H), 0.42- 0.20 (m, 4H)
1315[Figure (not displayed)]
MS (ESI) m/z 698.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.4 Hz, 1H), 8.65 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.42-4.34 (m, 2H), 4.20 (s, 2H), 3.63-3.57 (m, 5H), 2.90- 2.80 (m, 4H), 1.76 (s, 3H), 1.21 (d, J = 6.8 Hz, 3H)
1316[Figure (not displayed)]
MS (ESI) m/z 712.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 8.47 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.41-4.35 (m, 2H), 4.23-4.16 (m, 2H), 3.61 (s, 4H), 2.93 (s, 4H), 1.75 (s, 3H), 1.32 (s, 6H)
1317[Figure (not displayed)]
MS (ESI) m/z 676.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.45 (s, 1H), 7.59- 7.57 (m, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.38 (s, 2H), 4.20 (s, 2H), 3.65 (s, 4H), 2.67 (s, 4H), 2.60-2.48 (m, 2H), 1.74 (s, 3H), 1.35 (J = 21.6 Hz, 6H)
1318[Figure (not displayed)]
MS (ESI) m/z 7694.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 4.8 Hz, 1H), 8.51 (s, 1H), 8.31 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 6.54 (t, J = 57.2 Hz, 1H), 4.49 (bs, 2H), 4.39 (bs, 2H), 4.21 (bs, 2H), 3.60 (bs, 4H), 3.08 (t, J = 12.0 Hz, 2H), 3.08 (s, 3H), 2.17 (bs, 1H), 2.03 (bs, 4H) 1.76 (s, 3H)
1319[Figure (not displayed)]
MS (ESI) m/z 670.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.76 Hz, 1H), 8.62 (s, 1H), 8.41 (s, 1H), 7.60 (dd, J = 8.9 Hz, 2.4 Hz, 1H), 7.47 (d, J = 4.7 Hz, 1H), 7.42 (d, J = 2.5 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.57- 4.52 (m, 1H), 4.39 (d, J = 5.6 Hz, 2H), 4.17 (d, J = 5.28, 2H), 3.65 (d, J = 11.44, 2H), 3.95 (bs, 2H), 3.07 (s, 3H), 2.83 (bs, 1H), 2.07 (s, 4H), 1.76 (s, 3H), 0.94-0.85 (m, 4H)
1320[Figure (not displayed)]
MS (ESI) m/z 686.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1H), 8.82 (d, J = 4.8, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.77-4.76 (m, 4H), 4.55 (bs, 1H), 4.39 (s, 3H), 4.21 (s, 2H), 3.26-3.15 (m, 2H), 3.09-2.97 (m, 5H), 2.21-2.08 (m, 4H), 1.77 (s, 3H)
1321[Figure (not displayed)]
MS (ESI) m/z 652.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 6 8.74 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.66 (m, 2H), 7.53 (d, J = 4.4 Hz, 1H), 4.83 (s, 2H), 4.76 (s, 4H), 4.37 (bs, 4H), 4.04 (bs, 1H), 3.34-2.82 (m, 4H), 2.12 (s, 3H)
1322[Figure (not displayed)]
MS (ESI) m/z 664.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.64 (s, 1H), 7.76-7.73 (m, 1H), 7.69-7.66 (m, 2H), 7.52 (d, J = 4.8 Hz, 1H), 4.80 (s, 2H), 4.54 (t, J = 6.4 Hz, 2H), 4.47 (s, 4H), 4.35 (t, J = 6 Hz, 2H), 3.69 (t, J = 5.6 Hz, 1H), 3.42 (s, 4H), 2.0 (s, 3H)
1323[Figure (not displayed)]
MS (ESI) m/z 630.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.50 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 7.19 (s, 1H), 4.41 (t, J = 4.8 Hz, 2H), 4.24 (t, J = 4.8 Hz, 2H), 3.64 (s, 2H), 2.96 (m, 5H), 2.5 (m, 3H), 2.10 (m, 2H), 1.85 (s, 3H)
1324[Figure (not displayed)]
MS (ESI) m/z 652.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.85 (d, J = 4.81 Hz, 1H), 8.36 (s, 1H), 7.62-7.59 (m, 2H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.06 (bs, 1H), 4.44 (s, 2H), 4.33 (s, 2H), 3.29 (s, 6H), 2.60 (s, 3H), 1.92 (s, 3H)
1325[Figure (not displayed)]
MS (ESI) m/z 652.36 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 9.09 (s, 1H), 9.00 (s, 1H), 8.85 (d, J = 4.4 Hz, 1H), 8.38 (s, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.60 ( dd, J = 8.8, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.42 (s, 2H), 4.28 (s, 2H), 3.66 (s, 2H), 2.26 (s, 6H), 1.83 (s, 3H)
1326[Figure (not displayed)]
MS (ESI) m/z 631.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 8.97 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), 7.60 (dd, J = 9.2, 2.0 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.81 (d, J = 46.4 Hz, 2H), 4.47-4.38 (m, 4H), 4.26 (s, 2H), 3.65-3.30 (m, 2H), 2.86 (s, 3H), 1.77 (s, 3H)
1327[Figure (not displayed)]
MS (ESI) m/z 667.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.94 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.38 (s, 1H), 7.59 (dd, J = 9.2, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 4.39 (s, 2H), 4.25 (s, 2H), 3.88 (s, 2H), (q, J = 10.0 Hz, 2H), 2.54 (s, 3H), 1.73 (s, 3H)
1328[Figure (not displayed)]
MS (ESI) m/z 633.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.40 (bs, 1H), 10.08 (bs, 1H), (9.01 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), 7.60 (dd, J = 8.9, 2.5 Hz, 1H), 7.48 (d, J = 4.7 Hz, 1H), 7.45-7.33 (m, 3H), 7.21-7.18 (m, 1H), 4.88 (d, J = 47.2 Hz, 2H), 4.41 (t, J = 4.9 Hz, 2H), 4.27-4.13 (m, 4H), 3.70-3.55 (m, merged, 2H), 2.90 (s, 3H), 1.81 (s, 3H)
1329[Figure (not displayed)]
MS (ESI) m/z 625.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.34 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.4 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.40 (bs, 2H), 4.25 (bs, 2H), 2.74 (bs, 6H), 1.75 (s, 3H), 1.36 (bs, 4H)
1330[Figure (not displayed)]
MS (ESI) m/z 617.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.38 (bs, 1H), 10.15 (bs, 1H), 9.02 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.34 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 5.27 (d, J = 8.0 Hz, 1H), 4.40 (bs, 2H), 4.32-4.23 (m, 2H), 3.94 (t, J = 12.4 Hz, 1H), 3.78 (bs, 2H), 3.49 (bs, 2H), 3.24 (bs, 1H), 2.99 (s, 3H), 1.81 (s, 3H)
1332[Figure (not displayed)]
MS (ESI) m/z 655.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.61 (dd, J = 9.2, 2.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.42 (bs, 2H), 4.30 (bs, 2H), 2.82 (bs, 2H), 2.72 (s, 6H), 2.61 (bs, 2H) 1.30 (s, 9H)
1333[Figure (not displayed)]
MS (ESI) m/z 676.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.33 (bs, 1H), 9.75 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.38 (s, 1H), 7.61-7.58 (dd, J = 2.8, 9.2 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.97-4.79 (m, 2H), 4.39 (bs, 2H), 4.22 (bs, 2H), 3.88-3.48 (m, 6H), 1.79 (s, 3H), 1.45 (s, 3H), 1.40 (s, 3H)
1334[Figure (not displayed)]
MS (ESI) m/z 684.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.43 (s, 1H), 7.59 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.43 (s, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.38 (s, 2H), 4.21 (s, 2H), 4.08 (d, J = 11.2 Hz, 1H), 3.82- 3.05 (m, 5H), 2.67 (s, 1H), 2.50 (s, 3H), 1.76 (s, 3H)
1335[Figure (not displayed)]
MS (ESI) m/z 630.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.85 (s, 1H), 8.85 (d, J = 8.4 Hz, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.41 (m, 2H), 4.74 (bs, 1H), 4.42 (m, 2H), 4.23 (m, 4H), 3.52 (m, 2H), 3.32 (m, 2H). 2.91 (s, 3H), 1.78 (s, 3H), 1.49 (d, J = 6.8 Hz, 3H), 1.04 (d, J = 5.6 Hz, 1H)
1336[Figure (not displayed)]
MS (ESI) m/z 674.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.62 (d, J = 49.6 Hz, 2H), 4.40-4.35 (m, 2H), 4.25-4.15 (m, 2H), 3.75-3.55 (m, 4H), 3.30-3.00 (m, 4H), 1.79 (s, 3H), 1.15-.0.80 (m, 4H)
1337[Figure (not displayed)]
MS (ESI) m/z 642.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.37 (bs, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.70 (s, 1H), 8.38 (s, 1H), 7.60 (t, J = 6.8 Hz, 1H), 7.47-7.21 (m, 3H), 4.39 (s, 2H), 4.23 (s, 2H), 4.05 (bs, 2H), 3.93 (bs, 2H), 3.52 (bs, 2H), 2.99 (s, 3H), 1.79 (s, 3H), 1.26- 1.07 (m, 4H)
1338[Figure (not displayed)]
MS (ESI) m/z 674.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.39 (s, 1H), 7.60 (dd, J = 8.8, 2.0 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.83-4.72 (m, 2H), 4.39 (s, 2H), 4.23 (s, 2H), 3.98-3.53 (m, 8H), 1.77 (s, 3H), 1.03 (bs, 4H)
1339[Figure (not displayed)]
MS (ESI) m/z 708.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.27 (bs, 1H), 8.82 (d, J = 8.0 Hz, 1H), 8.67 (s, 1H), 8.43 (s, 1H), 7.59 (d, J = 6.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.42 (s, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.39 (s, 2H), 4.22 (s, 2H), 3.59-3.30 (m, 12H), 3.10 (s, 3H), 1.79 (s, 3H)
1340[Figure (not displayed)]
MS (ESI) m/z 692.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.57 (t, J = 8.0 Hz, 2H), 4.38 (bs, 4H), 4.20 (bs, 2H), 3.94 (bs, 1H), 3.07 (bs, 4H), 2.20 (bs, 4H), 1.76 (s, 3H)
1341[Figure (not displayed)]
MS (ESI) m/z 664.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.58 (s, 1H), 8.47 (s, 1H), 8.48 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.47-4.42 (m, 2H), 4.37 (bs, 2H), 4.18 (bs, 2H), 4.13-4.10 (m, 2H), 3.95-3.74 (m, 5H), 1.74 (s, 3H)
1342[Figure (not displayed)]
MS (ESI) m/z 655.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.27 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.46 (d, J = 4.0 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.43-4.35 (m, 2H), 4.25-4.15 (m, 2H), 4.13- 4.00 (m, 2H), 3.16- 3.10 (m, 1H), 2.97- 2.83 (m, 4H), 2.48-2.33 (m, 2H), 2.30 (s, 3H), 1.74 (s, 3H)
1343[Figure (not displayed)]
MS (ESI) m/z 683.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.40 (s, 2H), 4.23 (s, 2H), 3.95 (s, 2H), 3.57-3.40 (m, 4H), 3.30-3.15 (m, 4H), 1.83 (s, 3H), 1.46 (s, 6H)
1344[Figure (not displayed)]
MS (ESI) m/z 651.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.83 (d, J = 4.4 Hz, 1H), 8.36 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.48 (d, J = 4.4 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.80-4.60 (m, 1H), 4.40 (s, 2H), 4.25 (s, 2H), 3.55-3.30 (m, merged, 2H), 2.50-2.30 (m, 1H), 2.22-1.91 (m, 4H), 1.75 (s, 3H), 1.04-0.61 (m, 4H)
1345[Figure (not displayed)]
MS (ESI) m/z 635.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.40 (bs. 1H), 9.67 (bs, 1H), 8.96 (s, 1H), 8.82 (d, J = 4.7 Hz, 1H), 8.32 (s, 1H), 7.60 (dd, J = 8.92, 2.36 Hz, 1H), 7.47 (d, J = 4.7 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.9 Hz, 1H), 4.92-4.76 (m, 1H), 4.40 (t, J = 4.4 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 3.62-3.52 (m, 2H), 3.40-3.20 (m, 2H), 3.18 (t, J = 7.24 Hz, 2H), 2.88 (s, 3H), 2.31-2.17 (m, 2H), 1.82 (s, 3H)
1346[Figure (not displayed)]
MS (ESI) m/z 639.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.97 (s, 1H), 8.83 (d, J = 4.7 Hz, 1H), 8.37 (s, 1H), 7.59 (dd, J = 8.9, 2.4 Hz, 1H), 7.47 (d, J = 4.7 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H ), 7.34 (d, J = 9.0 Hz, 1H), 4.65-4.35 (m, 4H), 4.25 (t, J = 3.8 Hz, 2H), 2.85 (bs, 3H), 1.75 (s, 3H), 1.36 (s, 3H), 1.03 (bs, 2H), 0.72 (bs, 2H)
1347[Figure (not displayed)]
MS (ESI) m/z 624.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 8.86 (s, 1H), 8.79 (d, J = 4.4 Hz, 1H), 8.66 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.52 (s, 1H), 7.42 (d, J = 4.8 Hz, 1H), 6.52-6.38 (m, 1H), 5.89 (d, J = 16.0 Hz, 1H), 4.68 (d, J = 4.0 Hz, 2H), 4.39 (d, J = 13.2 Hz, 1H), 3.11 (t, J = 12.4 Hz, 2H), 2.82-2.65 (m, 1H), 2.40-2.10 (m, 8H), 0.72-0.45 (m, 2H)
1348[Figure (not displayed)]
MS (ESI) m/z 628.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6), 68.81 (d, J = 4.8 Hz, 1H), 6 8.62 (s, 1H), 8.43 (s, 1H), 7.59 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.45-7.42 (m, 2H), 7.35 (d, J = 8.8 Hz, 1H), 4.78 (bs, 1H), 4.37 (t, J = 5.1 Hz, 2H), 4.27 (t, J = 4.5 Hz, 2H), 3.45-3.43 (m, 2H), 3.32-2.8 (m, 4H), 2.75-2.56 (m, 2H), 1.93-1.90 (m, 2H), 1.74 (s, 3H)
1349[Figure (not displayed)]
MS (ESI) m/z 715.66 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.41 (s, 1H), 7.58 (dd, J = 8.8 Hz, 2.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 4.38 (s, 2H), 4.22 (s, 2H), 4.05 (s, 1H), 3.40-3.32 (m, 2H), 2.93 (s, 2H), 2.66-2.61 (m, 2H), 2.11-2.09 (m, 2H), 1.74 (s, 5H)
1350[Figure (not displayed)]
MS (ESI) m/z 694.59 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 8.41 (s, 1H), 7.59 (dd, J = 2.0, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.15 (bs, 1H), 4.39 (s, 2H), 4.21-4.16 (m, 2H), 4.14 (bs, 2H), 3.01 (bs, 6H), 1.77 (s, 3H), 1.21 (s, 6H)
1351[Figure (not displayed)]
MS (ESI) m/z 658.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 2.36 Hz, 1H), 8.74 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.9, 2.5 Hz, 1H), 7.47 (d, J = 4.7 Hz, 1H), 7.42 (d, J = 2.5 Hz, 2H), 7.37 (d, J = 9.0 Hz, 2H), 4.66 (d, J = 7.5 Hz, 2H), 4.40 (s, 2H), 4.24 (s, 2H), 4.14 (bs, 4H), 3.40 (s, 2H), 3.06 (s, 3H), 1.82 (s, 3H)
1352[Figure (not displayed)]
MS (ESI) m/z 652.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 6 8.74 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.66 (m, 2H), 7.53 (d, J = 4.4 Hz, 1H), 4.83 (s, 2H), 4.76 (s, 4H), 4.37 (bs, 4H), 4.04 (bs, 1H), 3.34-2.82 (m, 4H), 2.12 (s, 3H)
1353[Figure (not displayed)]
MS (ESI) m/z 692.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.83 (s, 1H), 8.75 (d, J = 4.6 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.69 (s, 1H), 7.66 (s, 1H), 7.52 (d, J = 4.6 Hz, 1H), 4.83 (s, 2H), 4.31 (bs, 1H), 3.43 (bs, 7H), 2.85 (s, 4H), 2.11 (s, 3H)
1354[Figure (not displayed)]
MS (ESI) m/z 636.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.18 (bs, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.38 (m, 2H), 3.79 (m, 2H,), 3.49 (m, 4H), 3.03 (m, 1H), 2.14 (s, 3H), 0.93 (m, 4H)
1355[Figure (not displayed)]
MS (ESI) m/z 686.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 8.83 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 1H), 7.53 (d, J = 4.8 Hz, 1H), 4.72 (s, 2H), 3.80 (bs, 4H), 3.39 (bs, 4H), 3.05-3.02 (m, 5H), 2.16 (s, 3H)
1356[Figure (not displayed)]
MS (ESI) m/z 660.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.6 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.68 (m, 2H), 7.53 (d, J = 4.6 Hz, 1H), 6.34 (m, 1H), 4.82 (s, 2H), 3.76-2.66 (m, 10H), 2.09 (s, 1H)
1357[Figure (not displayed)]
MS (ESI) m/z 658.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.33 (t, J = 53.6 Hz, 1H), 5.09 (s, 1H), 4.38 (t, J = 4.3 Hz, 2H), 4.21 (t, J = 5.7, 2H), 4.15-3.80 (m, 7H), 2.21 (bs, 2H), 1.76 (s, 3H)
1358[Figure (not displayed)]
MS (ESI) m/z 716.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.37-7.33 (m, 2H), 5.77 (d, J = 46 Hz, 1H), 4.39 (s, 2H), 4.22 (s, 2H), 3.24 (bs, 2H), 3.29-3.15 (m, 8H), 1.79 (s, 3H)
1359[Figure (not displayed)]
MS (ESI) m/z 766.56 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4 Hz, 1H), 8.66 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.39 (bs, 2H), 4.21 (bs, 2H), 3.68 (bs, 4H), 2.96 (bs, 2H), 2.78 (bs, 4H), 2.46 (s, 1H) 1.77 (s, 3H)
1360[Figure (not displayed)]
MS (ESI) m/z 726.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.53 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.49 (bs, 1H), 4.52 (bs, 1H), 4.21 (bs, 2H), 3.69 (d, J = 10.4 Hz, 2H), 3.50 (bs, 2H), 3.40 (bs, 2H), 3.21 (s, 3H), 2.89-2.85 (m, 2H), 2.11 (bs, 4H), 1.78 (s, 3H)
1361[Figure (not displayed)]
MS (ESI) m/z 724.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.8, 2.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.37 (s, 2H), 4.20 (s, 2H), 3.63 (bs, 4H), 2.84 (bs, 4H), 2.70-2.50 (m, 2H), 1.77 (s, 3H), 0.84-0.74 (m, 4H)
1362[Figure (not displayed)]
MS (ESI) m/z 755.45 [M + 1]+; 1H NMR (400 MHz, DMSO- d6) δ 12.44 (s, 1H), 8.83-8.79 (m, 3H), 7.76 (d, J = 8.4 Hz, 1H), 7.71- 7.67 (m, 2H), 7.61 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.75- 3.60 (m, 4H), 3.56 (s, 3H), 3.31 (q, J = 10.0 Hz, 2H), 2.90-2.80 (m, 4H), 2.00 (s, 3H)
1363[Figure (not displayed)]
MS (ESI) m/z 668.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 9.37 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.37 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.38 (s, 2H), 4.21 (s, 2H), 3.80-3.50 (m, 2H), 3.20-2.90 (m, 2H), 2.61 (s, 3H), 1.78 (s, 3H), 1.40-0.80 (m, 8H)
1364[Figure (not displayed)]
MS (ESI) m/z 642.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.87-4.75 (m, 4H), 4.39 (bs, 2H), 4.22 (bs, 2H), 3.56-3.14 (m, 8H), 2.41 (s, 1H), 1.78 (s, 3H)
1365[Figure (not displayed)]
MS (ESI) m/z 656.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.30 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 8.41 (s, 1H), 7.62- 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.41-7.36 (m, 2H), 4.40 (bs, 4H), 4.24 (bs, 2H), 3.48 (bs, 6H), 1.85 (s, 3H), 1.39 (s, 3H), 1.19 (bs, 2H), 0.82 (bs, 2H)
1366[Figure (not displayed)]
MS (ESI) m/z 686.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79-8.73 (m, 2H), 8.66 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.72-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.04 (t, J = 55.6 Hz, 1H), 4.82 (s, 2H), 3.59 (s, 4H), 3.02 (s, 4H), 2.06 (s, 3H), 0.90-0.78 (m, 4H)
1367[Figure (not displayed)]
MS (ESI) m/z 677.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 9.99 (bs, 1H), 8.82 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.71-7.66 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.45 (bs, 2H), 3.62 (bs, 4H), 3.27 (bs, 4H), 2.13 (s, 3H), 1.46 (bs, 6H)
1368[Figure (not displayed)]
MS (ESI) m/z 661.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.77 (d, J = 3.2 Hz, 1H), 8.67 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.71-7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.67 (s, 4H), 2.82 (s, 4H) 2.07 (s, 3H), 1.32-1.27 (m, 2H), 1.17-1.09 (m, 2H)
1369[Figure (not displayed)]
MS (ESI) m/z 682.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.4 Hz, 1H), 8.60 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 9.2, 2.4 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.60 (s, 2H), 4.52 (s, 2H), 4.43-4.38 (m, 4H), 4.33-4.28 (m, 2H), 4.20 (bs, 2H), 3.79 (bs, 1H), 1.89 (t, J = 6.8 Hz, 2H), 1.80 (s, 3H), 1.67-1.58 (m, 4H), 1.47 (t, J = 6.4 Hz, 2H)
1370[Figure (not displayed)]
MS (ESI) m/z 684.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.9 Hz, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.51 (bs, 1H), 4.39 (s, 2H), 4.21 (s, 2H), 3.68 (d, J = 10.4 Hz, 2H), 3.21-3.16 (m, 2H), 3.09 (s, 3H), 3.01 (t, J = 5.6 Hz, 2H), 2.21-2.15 (m, 2H), 2.12-2.06 (m, 2H), 1.77 (s, 3H), 1.10 (bs, 1H), 0.67 (d, J = 7.2 Hz , 2H), 0.44-0.38 (m, 2H)
1371[Figure (not displayed)]
MS (ESI) m/z 654.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.48 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.44 (s, 1H), 7.60 (dd, J = 9.2, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 5.25-4.89 (m, 2H), 4.63 (d, J = 10.4 Hz, 2H), 4.38 (s, 2H), 4.21 (s, 2H), 3.98 (bs, 2H), 3.18 (bs, 1H), 2.75 (bs, 2H), 1.78 (s, 3H), 0.86 (bs, 4H)
1378[Figure (not displayed)]
MS (ESI) m/z 608.1
1382[Figure (not displayed)]
MS (ESI) m/z 608.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 1H NMR (400 MHz, DMSO- d6) δ 9.05 (s, 1H), 8.44 (s, 1H), 7.94-7.86 (m, 2H), 7.64-7.54 (m, 4H), 7.46-7.40 (m, 2H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (d, J = 4.9 Hz, 2H), 4.29 (d, J = 4.9 Hz, 2H), 2.71 (s, 3H), 1.89 (s, 3H)
1390[Figure (not displayed)]
MS (ESI) m/z 650.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (d, J = 2.8 Hz, 2H), 7.35 (d, J = 9.0 Hz, 1H), 6.29 (s, 1H), 4.39 (d, J = 5.0 Hz, 2H), 4.26 (d, J = 4.9 Hz, 2H), 2.91-2.78 (m, 4H), 2.71 (s, 3H), 2.35- 2.15 (m, 2H), 1.85 (s, 3H)
1395[Figure (not displayed)]
MS (ESI) m/z 714.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.8 Hz, 1H), 8.54 (s, 1H), 8.48 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.39 (d, J = 9.0 Hz, 1H), 4.54 (s, 2H), 4.43 (t, J = 5.1 Hz, 2H), 4.24 (t, J = 5.1 Hz, 2H), 3.82-3.40 (m, 10H), 1.83 (s, 3H)
1396[Figure (not displayed)]
MS (ESI) m/z 708.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.76 (dd, J = 8.3, 0.5 Hz, 1H), 7.71-7.65 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.53 (s, 2H), 4.06-2.83 (m, 8H), 2.13 (s, 3H)
1397[Figure (not displayed)]
MS (ESI) m/z 708.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.51-7.47 (m, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.46 (t, J = 54.6 Hz, 1H), 4.54 (s, 4H), 4.41 (t, J = 4.9 Hz, 2H), 4.21 (t, J = 4.8 Hz, 2H), 4.10 (s, 4H), 2.75 (t, J = 4.7 Hz, 4H), 1.75 (s, 3H)
1398[Figure (not displayed)]
MS (ESI) m/z 650.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (d, J = 2.8 Hz, 2H), 7.35 (d, J = 9.0 Hz, 1H), 6.29 (s, 1H), 4.39 (d, J = 5.0 Hz, 2H), 4.26 (d, J = 4.9 Hz, 2H), 2.91-2.78 (m, 4H), 2.71 (s, 3H), 2.35- 2.15 (m, 2H), 1.85 (s, 3H)
1399[Figure (not displayed)]
MS (ESI) m/z 842.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 8.90 (d, J = 4.9 Hz, 1H), 8.72 (ddd, J = 4.6, 1.7, 0.9 Hz, 1H), 8.65 (s, 1H), 8.60 (s, 1H), 8.30-8.25 (m, 1H), 8.21 (td, J = 7.7, 1.7 Hz, 1H), 7.80-7.72 (m, 2H), 7.72-7.68 (m, 2H), 7.66 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 3.09 (s, 3H), 1.94 (s, 3H), 1.77 (t, J = 18.9 Hz, 2H)
1400[Figure (not displayed)]
MS (ESI) m/z = 740.3 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 9.59-9.49 (b, 1H), 8.83 (d, J = 4.6 Hz, 1H), 8.70 (s, 1H), 8.42 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.38 (d, J = 8.9 Hz, 1H), 4.43-4.36 (m, 2H), 4.24 (t, J = 4.8 Hz, 2H), 3.61-3.49 (m, 2H), 3.34-3.20 (m, 2H), 2.49-2.39 (m, 2H), 2.00-1.92 (m, 2H), 1.85 (s, 3H), 1.39 (s, 6H). Remaining protons partially obscured by water peak
1401[Figure (not displayed)]
MS (ESI) m/z = 738.3 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 8.83 (d, J = 4.9 Hz, 1H), 8.67 (s, 1H), 8.42 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.7 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.23 (t, J = 4.9 Hz, 2H), 2.39- 2.25 (m, 2H), 1.82 (s, 3H), 1.40-0.45 (b, 4H). Remaining protons appear as very broad signals and/or are partially obscured by water peak
1402[Figure (not displayed)]
MS (ESI) m/z = 627.3 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 10.20-10.10 ppm (b, 1H), 9.15 (s, 1H), 8.74 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.78-7.75 (m, 1H), 7.71-7.68 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 15 Hz, 1H), 7.19 (dt, J = 7.3, 15 Hz, 1H), 4.97-4.79 (m, 2H), 4.88 (s, 2H), 4.35-4.13 (m, 2H), 3.75-3.53 (m, 2H), 2.91 (s, 3H), 2.15 (s, 3H)
1403[Figure (not displayed)]
MS (ESI) m/z = 686.2 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 68.77 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.65 (s, 1H), 7.77-7.73 (m, 1H), 7.71-7.66 (m, 2H), 7.53 (d, J = 4.8 HZ, 1H), 6.37 (bt, J = 55 Hz, 1H), 4.81 (s, 2H), 3.25 (s, 3H), 2.37-2.18 (b, 2H), 2.11 (s, 3H). Remaining protons are (partially) obscured by water peak
1404[Figure (not displayed)]
MS (ESI) m/z = 674.4 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 68.75 (s, 1H), 8.75 (d, J = 4.7 Hz, 1H), 8.59 (s, 1H), 7.74 (dd, J = 8.1, 0.5 Hz, 1H), 7.69-7.64 (m, 2H), 7.43 (dd, J = 4.7, 0.3 Hz, 1H), 6.22 (tt, J = 55.7, 4.4 Hz, 1H), 4.81 (s, 2H), 3.85 (s, 3H), 3.71-3.67 (m, 4H), 2.84 (dt, J = 15.7, 4.2 Hz, 2H), 2.78-2.72 (m, 4H), 2.06 (s, 3H)
1405[Figure (not displayed)]
MS (ESI) m/z = 722.5 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 68.82 (s, 1H), 8.74 (d, J = 4.7 Hz, 1H), 8.62 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.67 (dd, J = 8.4, 2.2 Hz, 1H), 7.61 (dd, J = 2.2, 0.4, 1H), 7.43 (d, J = 4.7 Hz, 1H), 4.82 (s, 2H), 4.59-4.53 (m, 2H), 3.86 (s, 3H), 3.69-3.62 (m, 2H), 2.16 (s, 3H). Remaining protons appear as very broad signals and/or are partially obscured by water peak
1406[Figure (not displayed)]
MS (ESI) m/z = 714.5 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 10.38-10.18 (b, 1H), 8.76 (d, J = 4.7 Hz, 1H), 8.75 (s, 1H), 8.66 (s, 1H), 7.78-7.66 (m, 3H), 7.55 (d, J = 4.7 Hz, 1H), 6.59 (t, J = 52.6 Hz, 1H), 4.82 (s, 2H), 4.78- 4.68 (m, 1H), 4.24-4.14 (m, overlapping with water peak), 3.76-3.58 (m, overlapping with water peak), 3.12 (s, 3H), 2.47-2.37 (m, 2H), 2.37-2.26 (m, 2H), 2.21-2.13 (m, 2H), 2.10-2.01 (m, 2H)
1407[Figure (not displayed)]
MS (ESI) m/z = 686.1 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 68.79 (b, 1H), 8.77 (d, J = 4.7 Hz, 1H), 8.67 (s, 1H), 7.79-7.74 (m, 1H), 7.71- 7.67 (m, 2H), 7.54 (d, J = 4.7 Hz, 1H), 6.58- 5.69 (b, 1H), 4.84 (s, 2H), 3.33 (t, J = 6.6 Hz, 1H), 3.28 (s, 3H), 2.08 (s, 3H). Remaining protons appear as broad signals and/or are (partially) obscured by water peak
1408[Figure (not displayed)]
MS (ESI) m/z = 819.2 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 12.98 (bs, 1H), 10.80-10.54 (b, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.79 (s, 1H), 8.75 (s, 1H), 7.77 (dd, J = 8.3, 0.5 Hz, 1H), 7.72-7.66 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 6.40 (tt, J = 53.6, 2.8 Hz, 1H), 5.27-5.17 (m, 1H), 5.00-4.90 (m, 4H), 4.82 (s, 2H), 4.12 (bs, 2H), 3.99-3.85 (m, 2H), 3.76-3.55 (m, 4H), 2.11-1.93 (m, 4H), 1.96 (s, 3H)
1409[Figure (not displayed)]
MS (ESI) m/z = 840.5 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 13.15-12.95 (b, 1H), 10.75- 10.55 (b, 1H), 9.26 (dd, J = 2.4, 0.7 Hz, 1H), 8.89 (dd, J = 4.8, 1.6 Hz, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.52 (ddd, J = 8.1, 2.4, 1.6 Hz, 1H), 8.46 (s, 1H), 7.74-7.64 (m, 3H), 7.62 (dd, J = 2.2, 0.5 Hz, 1H), 7.59 (d, J = 4.8 Hz, 1H), 6.37 (tt, J = 53.7, 3.1 Hz, 1H), 4.77 (s, 2H), 4.10 (bs, 4H), 3.97-3.82 (m, 2H), 3.72- 3.50 (m, 4H), 2.07-1.94 (m, 4H), 1.87 (s, 3H)
1410[Figure (not displayed)]
MS (ESI) m/z = 791.4 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 12.44 (s, 1H), 10.60-10.50 (b, 1H), 8.80 (s, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.78 (s, 1H), 7.77 (dd, J = 8.3, 0.5 Hz, 1H), 7.70 (dd, J = 8.3, 2.1 Hz, 1H), 7.67 (dd, J = 2.1, 0.5 Hz, 1H), 7.62 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.27-3.90 (m, 6H), 3.79-3.56 (m, 4H expected; partially obscured by water peak), 3.55 (s, 3H expected; partially obscured by water peak), 2.12-1.95 (m, 4H), 2.00 (s, 3H), 1.73 (t, J = 19 Hz, 3H)
1411[Figure (not displayed)]
MS (ESI) m/z = 833.3 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) 6 12.65 (bs, 1H), 10.59 (bs, 1H), 8.78 (d, J = 4.8 Hz, 1H), 8.75 (s, 1H), 8.71 (s, 1H), 7.74 (dd, J = 8.3, 0.5 Hz, 1H), 7.67 (dd, J = 8.3, 2.1, 1H), 7.64 (dd, J = 2.1, 0.5 Hz, 1H), 7.59 (d, J = 4.8 Hz, 1H), 5.24-5.15 (m, 1H), 4.98-4.85 (m, 4H), 4.79 (s, 2H), 4.21-3.87 (m, 4H), 3.74-3.54 (m, 4H), 2.10-1.91 (m, 4H), 1.92 (s, 3H), 1.70 (t, J = 19.3 Hz, 3H)
1412[Figure (not displayed)]
MS (ESI) m/z = 854.4 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) d/ppm = 13.13-13.93 (b, 1H), 10.65-10.49 (b, 1H), 9.26 (dd, J = 2.4, 0.8 Hz, 1H), 8.89 (dd, J = 4.9, 1.6 Hz, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.52 (ddd, J = 8.1, 2.4, 1.6 Hz, 1H), 8.46 (s, 1H), 7.73 (dd, J = 8.4, 0.4 Hz, 1H), 7.69 (ddd, J = 8.1, 3.3, 0.8 Hz, 1H), 7.66 (dd, J = 8.4, 2.2 Hz, 1H), 7.62 (dd, J = 2.2, 0.4 Hz, 1H), 7.59 (d, J = 4.8 Hz, 1H), 4.77 (s, 2H), 4.24-3.90 (m, 6H expected, overlapping with water peak), 3.71-3.51 (m, 4H), 2.08-1.93 (m, 4H), 1.87 (s, 3H), 1.70 (t, J = 19.4 Hz, 3H)
1413[Figure (not displayed)]
MS (ESI) m/z 702.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.81-8.72 (m, 2H), 8.64 (s, 1H), 7.79-7.72 (m, 1H), 7.71 −7.64 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.32-3.89 (m, 6H), 3.64 (m, 4H), 2.07 (d, J = 1.6 Hz, 6H), 2.00 (s, 3H), 1.74 (t, J = 19.6 Hz, 3H)
1414[Figure (not displayed)]
LCMS (ESI) m/z 702.5 [M + 1]+
1415[Figure (not displayed)]
MS (ESI) m/z 629.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 22.2 Hz, 1H), 8.78 (m, 1H), 8.44 (d, J = 17.1 Hz, 1H), 8.11 (d, J = 57.3 Hz, 1H), 7.57 (m, 1H), 7.48-7.40 (m, 2H), 7.34 (dd, J = 12.2, 9.0 Hz, 1H), 4.39 (m, 2H), 4.26 (d, J = 5.4 Hz, 2H), 3.47-3.31 (m, 2H), 3.25 (dd, J = 13.1, 9.7 Hz, 1H), 2.29 (m, 1H), 2.22-2.11 (m, 1H), 2.11-2.01 (m, 1H), 1.99 (d, J = 2.0 Hz, 3H), 1.82 (d, J = 14.3 Hz, 1H), 1.46 (s, 1H), 1.26 (s, 3H)
1418[Figure (not displayed)]
MS (ESI) m/z 644.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.71 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.40 (s, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.1 Hz, 2H), 4.31-4.22 (m, 4H), 3.62 (d, J = 12.1 Hz, 2H), 3.40 (t, J = 13.0 Hz, 2H), 3.20 (q, J = 11.4 Hz, 2H), 2.90 (s, 3H), 2.70 (s, 3H), 2.53 (s, 3H), 2.00 (s, 3H)
1419[Figure (not displayed)]
MS (ESI) m/z 588.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.63 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.41 (s, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.33 (q, J = 1.6 Hz, 1H), 5.97 (q, J = 1.9 Hz, 1H), 4.54-4.48 (m, 2H), 4.42 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.1 Hz, 2H), 2.67 (s, 3H), 1.99 (s, 3H)
1421[Figure (not displayed)]
MS (ESI) m/z 619.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.17 (bs, 1H), 7.92 (bs, 1H), 7.52 (d, J = 5.2 Hz, 1H), 7.34-7.27 (m, 2H), 7.14 (bs, 1H), 4.35 (bs, 2H), 4.26 (bs, 2H), 4.04-3.97 (m, 2H), 3.74-3.67 (m, 2H), 2.34 (s, 3H), 1.82 (s, 3H), 1.78 (s, 3H)
1422[Figure (not displayed)]
MS (ESI) m/z 676.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.45 (s, 1H), 7.59- 7.57 (m, 1H), 7.45 (d, J = 4.80, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.38 (s, 2H), 4.20 (s, 2H), 3.65 (s, 4H), 2.67 (s, 4H), 2.60-2.48 (m, 2H), 1.74 (s, 3H), 1.35 (J = 21.6 Hz, 6H)
1423[Figure (not displayed)]
MS (ESI) m/z 660.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.64 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.12 Hz, 1H), 7.68 (m, 2H), 7.53 (d, J = 4.64 Hz, 1H), 6.34 (m, 1H), 4.82 (s, 2H), 3.76- 2.66 (m, 10H), 2.09 (s, 1H)
1424[Figure (not displayed)]
MS (ESI) m/z 662.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.42 (s, 1H), 7.61 (dd, J = 8.8 Hz, 2.8 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.41 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.96- 4.67 (m, 2H), 4.40-4.21 (m, 5H), 3.57-3.36 (m, 8H), 1.84 (s, 3H), 1.37 (d, J = 6.0 Hz, 3H)
1425[Figure (not displayed)]
MS (ESI) m/z 688.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz,1H), 8.67 (s, 1H), 8.44 (s, 1H), 7.60 (dd, J = 2.8, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.58-4.48 (m, 1H), 4.44-4.41 (m, 2H), 4.39-4.36 (m, 2H), 3.56-3.53 (m, 4H), 3.30-3.28 (m, 1H), 3.17-2.95 (m, 4H), 2.22-2.19 (m, 2H), 1.84 (s, 3H), 1.14- 0.77 (m, 4H)
1427[Figure (not displayed)]
MS (ESI) m/z 697.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.41 (s, 1H), 7.59 (dd, J = 8.8, 2.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.39 (t, J = 4.4 Hz, 2H), 4.24 (t, J = 4.4 Hz, 2H), 3.81-3.75 (m, 1H), 3.31 (bs, 3H), 2.45 (s, 3H), 2.32-2.23 (m, 1H), 2.11-1.93 (m, 3H), 1.92-1.66 (m, 5H)
1428[Figure (not displayed)]
MS (ESI) m/z 702.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.42 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H) 7.36 (d, J = 9.2 Hz, 1H), 4.52 (s, 2H), 4.37-4.40 (m, 2H), 4.23-4.26 (m, 1H), 4.18-4.21 (m, 2H), 3.03 (s, 3H), 2.94-2.97 (m, 2H), 2.66-2.72 (m, 2H), 1.71-1.75 (m, 7H), 0.64-0.68 (m, 4H)
1426[Figure (not displayed)]
MS (ESI) m/z 724.56 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.8 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.74 (s, 1H), 4.63 (s, 1H), 4.39 (t, J = 4.4 Hz, 2H), 4.21 (t, J = 4.4 Hz, 2H), 3.69 (bs, 4H), 2.88 (bs, 4H), 2.72 (bs, 4H), 1.7(s, 3H)
1430[Figure (not displayed)]
MS (ESI) m/z 720.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.60 (dd, J = 2.4, 6.4 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 6.08 (t, J = 55.6 Hz, 1H), 4.38 (d, J = 4.4 Hz, 2H), 4.25 (bs, 1H), 4.19 (bs, 2H), 3.08 (bs, 2H), 3.03 (s, 3H), 2.92 (bs, 2H), 1.77 (bs, 7H), 0.48-0.78 (m, 4H)
1431[Figure (not displayed)]
MS (ESI) m/z 722.55 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.39 (s, 1H) 7.61 (dd, J = 2.4, 9.2 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42-7.35 (m, 2H), 6.52 (t, J = 52 Hz, 1H), 4.62-4.56 (m, 1H), 4.39 (bs, 2H), 4.21 (bs, 2H,), 3.38-3.34 (m, 4H), 3.09 (s, 3H), 2.32-2.26 (m, 2H), 2.12-2.09 (m, 2H), 1.76 (s, 3H), 1.44 (s, 6H)
1429[Figure (not displayed)]
MS (ESI) m/z 704.54 [M − F1]; 1H NMR (400 MHz, DMSO-d6) 613.2 (bs, 1H), 9.11 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.38 (s, 1H), 7.60 (dd, J = 2.8, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H) 7.36 (d, J = 8.8 Hz, 1H), 4.74-4.62 (d, J = 46.8 Hz, 2H), 4.60-4.57 (m, 1H), 4.39 (bs, 2H), 4.21 (bs, 2H), 3.66-3.58 (m, 2H), 3.30-3.24 (m, 2H), 3.09 (s, 3H), 2.26-2.20 (m, 2H), 2.11-2.08 (m, 2H), 1.76 (s, 3H), 1.38 (s, 6H)
1433[Figure (not displayed)]
MS (ESI) m/z 708.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.2 Hz, 1H), 8.65 (s, 1H), 8.41 (s, 1H), 7.59 (d, J = 8.6 Hz, 1H), 7.47-7.43 (m, 2H), 7.35 (d, J = 8.8 Hz, 1H), 6.51 (t, J = 53.4 Hz, 1H), 4.38 (s, 4H), 4.21 (s, 2H), 3.07 (bs, 5H), 2.52 (s, 2H), 2.17 (bs, 2H), 2.02 (bs, 2H), 1.75 (s, 3H), 1.11 (t, J = 6.3 Hz, 3H)
1434[Figure (not displayed)]
MS (ESI) m/z 667.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.32 (bs, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.44 (dd, J = 15.6 Hz, 2H), 7.35 (d, J = 9.2 Hz, 1H), 4.59 (s, 2H), 4.53 (s, 2H), 4.38 (bs, 4H), 4.24- 4.20 (m, 4H), 3.91- 3.88 (m, 1H), 2.17 (bs, 2H), 2.01 (t, J = 9.6 Hz, 2H), 1.82 (s, 3H), 1.78-1.71 (m, 2H)
1432[Figure (not displayed)]
MS (ESI) m/z 708.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (dd, J = 4.8 Hz, 2 Hz, 1H), 8.61 (d, J = 2 Hz, 1H), 8.40 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.46 (dd, J = 4.8 Hz, 2 Hz, 1H), 7.43 (d, J = 4.0 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 4.99 (bs, 4H), 4.58 (bs, 1H), 4.39 (s, 2H), 4.21 (s, 2H), 4.0 (bs, 2H), 3.70 (bs, 2H), 3.28 (bs, 1H), 3.09 (s, 3H), 2.33-2.00 (m, 4H), 1.76 (s, 3H)
1436[Figure (not displayed)]
MS (ESI) m/z 682.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 9.66 (bs, 1H), 8.80 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.65-4.45 (m, 8H), 4.40-4.35 (m, 2H), 4.25-4.15 (m, 2H), 2.91 (bs, 1H), 1.80 (s, 3H), 1.17 (s, 3H), 1.06 (s, 3H), 0.85-0.55 (m, 2H)
1437[Figure (not displayed)]
MS (ESI) m/z 667.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.32 (bs, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.44 (dd, J = 15.6 Hz, 2H), 7.35 (d, J = 9.2 Hz, 1H), 4.59 (s, 2H), 4.53 (s, 2H), 4.38 (bs, 4H), 4.24- 4.20 (m, 4H), 3.91- 3.88 (m, 1H), 2.17 (bs, 2H), 2.01 (t, J = 9.6 Hz, 2H), 1.82 (s, 3H), 1.78-1.71 (m, 2H)
1435[Figure (not displayed)]
MS (ESI) m/z 718.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.78-4.59 (m, 4H), 4.40-4.30 (m, 6H), 4.23-4.18 (m, 2H), 3.35-3.15 (m, 2H), 2.80-2.65 (m, 2H), 1.80 (s, 3H), 1.47 (s, 3H)
1439[Figure (not displayed)]
MS (ESI) m/z 692.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.44 (s, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.54 (t, J = 54.8 Hz, 1H), 4.38 (d, J = 4.8 Hz, 2H), 4.22 (d, J = 4.8 Hz, 2H), 4.10 (d, J = 12 Hz, 1H), 3.93 (d, J = 12.4 Hz, 1H), 3.41-3.32 (m, 2H), 3.16-3.13 (m, 3H), 2.02 (bs, 1H),1.76 (s, 3H), 0.53-0.41 (m, 4H)
1440[Figure (not displayed)]
MS (ESI) m/z 693.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.33 (s, 1H), 7.65-7.58 (m, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.40 (t, J = 62.4 Hz, 1H), 4.41 (s, 2H), 4.28 (d, J = 5.2 Hz, 2H), 3.51-3.05 (m, 8H), 2.50 (bs, 2H), 1.82 (s, 3H), 1.77 (s, 1H)
1438[Figure (not displayed)]
MS (ESI) m/z 710.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.46 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.39 (d, J = 4.8 Hz, 2H), 4.29 (bs, 2H), 3.96 (dd, J = 14, 5.2 Hz, 1H), 3.87 (bs, 2H), 3.71 (bs, 1H), 3.59 (t, J = 9.2 Hz, 1H), 3.27 (bs, 1H), 2.90 (d, J = 12.8 Hz, 1H), 2.26 (bs, 1H), 1.76 (s, 3H), 0.58 (d, J = 6.4 Hz, 2H), 0.46 (s, 2H)
1443[Figure (not displayed)]
MS (ESI) m/z 656.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.07 (s, 1H), 8.75 (d, J = 4.8, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 6.8 Hz, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.47 (d, J = 44 Hz, 2H), 3.66 (bs, 4H), 2.96 (bs, 1H), 2.74 (s, 3H), 2.07-2.08 (m, 4H), 1.23 (s, 3H)
1444[Figure (not displayed)]
MS (ESI) m/z 650.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.29 (bs, 1H), 8.83 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.46 (bs, 2H), 3.53 (bs, 6H), 2.14 (s, 3H), 1.39 (s, 3H), 1.20 (bs, 2H), 0.83 (bs, 2H)
1441[Figure (not displayed)]
MS (ESI) m/z 728.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.60-7.58 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.38 (bs, 2H), 4.25-4.19 (m, 3H), 3.35-3.30 (m, 2H), 3.07(s, 5H), 2.66-2.59 (m, 2H), 1.92 (d, J = 9.2 Hz, 2H), 1.78-1.72 (m, 5H)
1446[Figure (not displayed)]
MS (ESI) m/z 682.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.56-4.41 (m, 2H), 3.77-3.06 (m, 8H), 2.23 (s, 3H), 1.23-0.72 (m, 6H)
1447[Figure (not displayed)]
MS (ESI) m/z 664.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.00 (bs, 1H), 8.83 (bs, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.64 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.37 (bs, 2H), 3.85-3.40 (m, 6H), 2.90-2.80 (m, 1H), 2.13 (s, 3H), 1.38 (s, 3H), 1.07 (s, 3H), 0.95-0.75 (m, 2H)
1445[Figure (not displayed)]
MS (ESI) m/z 668.45 [M + 1]+; 1; H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.60 (d, J = 48.4 Hz, 2H), 3.80- 3.50 (m, 4H), 3.30-2.80 (m, 4H), 2.09 (s, 3H), 1.20-0.80 (m, 4H)
1449[Figure (not displayed)]
MS (ESI) m/z 688.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.72-4.54 (m, 2H), 4.32 (bs, 2H), 3.14-2.67 (m, 8H), 2.10 (s, 3H), 1.48-1.45 (m, 3H)
1450[Figure (not displayed)]
MS (ESI) m/z 668.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.74 (bs, 1H), 8.46 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69-7.66 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 5.74 (d, J = 34.0 Hz, 2H), 5.10 (s, 1H), 4.98 (s, 1H), 4.83 (s, 2H), 4.40 (d, J = 20.8 Hz, 2H), 3.96 (bs, 2H), 3.65 (m, 2H), 3.54 (m, 2H), 3.29 (bs, 2H), 2.14 (s, 3H)
1448[Figure (not displayed)]
MS (ESI) m/z 674.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.75 (d, J = 4.4 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.91-4.83 (m, 6H), 4.12 (bs, 1H), 3.79 (bs, 4H), 3.27 (bs, 4H), 2.10 (s, 3H)
1452[Figure (not displayed)]
MS (ESI) m/z 670.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.76 (bs, 1H), 8.84 (s, 1H), 8.76 (d, J = 4.4 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 2H), 7.54 (d, J = 4.8 Hz, 2H), 4.83 (s, 2H), 4.72 (d, J = 46.8 Hz, 2H), 4.46 (d, J = 14.0 Hz, 2H), 3.85-3.50 (m, 4H), 3.40-3.30 (m, 2H), 2.15 (s, 3H), 1.40 (s, 6H)
1453[Figure (not displayed)]
MS (ESI) m/z 670.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.78 (bs, 1H), 8.83 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.71-7.64 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.32 (bs, 2H), 3.85- 3.30 (m, 8H), 2.13 (s, 3H), 1.50 (d, J = 21.2 Hz, 6H)
1451[Figure (not displayed)]
MS (ESI) m/z 664.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.36 (m, 2H), 3.71-3.57 (m, 4H), 3.30-3.18 (m, 4H), 2.15 (s, 3H), 2.21 (s, 3H), 0.60-0.51 (m, 4H)
1455[Figure (not displayed)]
MS (ESI) m/z 688.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8, 1H), 6.45- 6.14 (m, 1H), 4.82 (s, 2H), 3.98-3.69 (m, 4H), 3.17 (m, 4H), 2.11 (s, 3H), 1.29 (s, 6H)
1456[Figure (not displayed)]
MS (ESI) m/z 674.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.67 (t, J = 8.4 Hz, 2H), 7.53 (d, J = 4.8 Hz, 1H), 6.26 (t, J = 56 Hz, 1H), 4.83 (s, 2H), 4.36 (bs, 2H), 3.73 (bs, 2H), 3.37 (bs, 6H), 2.40 (bs, 2H), 2.13 (s, 3H)
1454[Figure (not displayed)]
MS (ESI) m/z 684.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8 Hz, 1H), 7.70-7.66 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.74-4.60 (m, 2H), 4.47 (d, J = 13.6 Hz, 2H), 3.75 (d, J = 11.2 Hz, 2H), 3.60- 3.53 (m, 2H), 3.31-3.28 (m, 2H), 2.21-2.15 (m, 5H) 1.42 (s, 6H)
1458[Figure (not displayed)]
MS (ESI) m/z 706.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.96 (bs, 1H), 8.84 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69 (dd, J = 8.4, 2.0 Hz, 1H), 7.65 (d, J = 2.0 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.40-4.36 (m, 2H), 3.74-3.72 (m, 2H), 3.29 (bs, 6H), 2.45-2.38 (m, 2H), 2.14 (s, 3H), 1.98-1.93 (m, 2H)
1459[Figure (not displayed)]
MS (ESI) m/z 642.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.69 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.65 (s, 1H), 7.53 (d, J = 4.8 Hz, 1H), 5.12-4.93 (m, 2H), 4.84 (s, 2H), 4.44 (dd, J = 42.4 Hz, 14.4 Hz, 1H), 3.54-3.51 (m, 4H), 3.00 (s, 3H), 2.50-2.43 (m, 1H), 2.14 (s, 3H)
1457[Figure (not displayed)]
MS (ESI) m/z 656.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 2H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.65-4.50 (m, 2H), 4.38 (d, J = 13.6 Hz, 2H), 3.46 (bs, 4H), 3.32 (bs, 4H), 2.19-2.06 (m, 5H)
1461[Figure (not displayed)]
MS (ESI) m/z 633.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 9.51 (bs, 1H), 9.12 (s, 1H), 8.74 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.76 (d, J = 9.1 Hz, 1H), 7.81-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.56 (s, 1H), 4.87 (s, 2H), 4.30-4.10 (m, 2H), 3.80 (bs, 1H), 3.01 (bs, 4H), 2.19 (s, 3H), 1.10-0.84 (m, 4H)
1462[Figure (not displayed)]
MS (ESI) m/z 639.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.07 (bs, 1H), 10.26 (bs, 1H), 9.12 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.57 (s, 1H), 5.00-4.85 (m, 4H), 4.29-3.95 (m, 2H), 3.90-3.80 (m, 2H), 3.60-3.45 (m, 2H), 3.10-2.90 (m, 2H), 2.18 (s, 3H)
1460[Figure (not displayed)]
MS (ESI) m/z 708.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.66 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.66-4.36 (m, 5H), 3.91-3.78 (m, 4H), 2.95 (bs, 3H), 2.13 (s, 3H)
1464[Figure (not displayed)]
MS (ESI) m/z 690.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.04 (bs, 1H), 8.81-8.75 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 10.0 Hz, 1H), 7.53 (d, J = 4.4 Hz, 1H), 4.83 (s, 2H), 4.36-4.02 (m, 4H), 3.69-3.59 (m, 4H), 3.36-2.9 (m, 4H), 2.11 (s, 3H)
1465[Figure (not displayed)]
MS (ESI) m/z 680.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s,1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.49-4.43 (m, 2H), 3.76-3.46 (m, 8H), 3.26 (s, 3H), 2.49 (s, 1H), 2.12 (s, 3H), 1.25 (bs, 2H), 0.97 (bs, 2H)
1463[Figure (not displayed)]
MS (ESI) m/z 657.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.62 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.70-7.68 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.62-6.34 (m, 2H), 4.86 (s, 2H), 3.41-3.24 (m, 4H), 3.15-2.95 (m, 2H), 2.87 (bs, 2H), 2.16 (s, 3H)
1467[Figure (not displayed)]
MS (ESI) m/z 686.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.57-4.55 (m, 4H), 4.24 (d, 2H), 3.21-3.15 (m, 2H), 2.41 (s, 1H), 2.08-2.04 (m, 5H), 1.55 (s, 2H)
1468[Figure (not displayed)]
MS (ESI) m/z 661.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (bs, 1H), 9.07 (s, 1H), 8.76 (s, 1H), 8.61 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69 (s, 2H), 7.53 (s, 1H), 4.87 (s, 2H), 3.90 (s, 2H), 3.50-3.30 (m, merged, 2H), 2.55 (s, 3H), 2.09 (s, 3H)
1466[Figure (not displayed)]
MS (ESI) m/z 674.47 [M + 1]+; 1; H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (bs, 1H), 7.67 (s, 1H), 7.53 (d, J = 4.4 Hz, 1H), 6.31 (t, J = 53.2 Hz, 1H), 4.82 (s, 2H), 3.79 (bs, 4H), 3.11 (bs, 4H), 2.64-2.59 (m, 1H), 2.09 (s, 3H), 1.21 (bs, 3H)
1470[Figure (not displayed)]
MS (ESI) m/z 674.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.74 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.44 (s, 1H), 7.61- 7.58 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.38 (d, J = 8.8 Hz, 1H), 5.73 (d, J = 30.4 Hz, 2H), 5.09 (s, 1H), 4.98 (s, 1H), 4.40 (d, J = 4.8 Hz, 2H), 4.31 (bs, 2H), 4.24 (d, J = 4.8 Hz, 2H), 3.96 (bs, 2H), 3.63 (m, 2H), 3.32-3.18 (m, 4H), 1.84 (s, 3H)
1471[Figure (not displayed)]
MS (ESI) m/z 724.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.45 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.39 (s, 2H), 4.32-4.23 (m, 4H), 3.28-2.86 (m, 4H), 1.83 (s, 3H), 1.30-1.21 (m, 4H)
1469[Figure (not displayed)]
MS (ESI) m/z 704.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.9 Hz, 1H), 8.70 (s, 1H), 8.40 (s, 1H), 7.55 (dd, J = 2.4, 8.8 Hz, 1H), 7.50 (d, J = 4.9 Hz, 1H), 7.31 (d, J = 2.8 Hz, 2H), 4.46 (t, J = 4.9 Hz, 2H), 4.34 (t, J = 4.9 Hz, 2H), 4.10 (bs, 4H), 3.72 (bs, 4H), 3.61 (s, 2H), 2.11 (s, 3H), 1.99-1.80 (m, 4H), 1.03 (t, J = 7.4 Hz, 6H)
1473[Figure (not displayed)]
MS (ESI) m/z 698.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.69 (bs, 1H), 8.45 (s, 1H), 7.59 (dd, J = 2.4, 9.2 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.39 (s, 2H), 4.22 (s, 4H), 3.54 (bs, 6H), 1.98-1.64 (m, 2H), 1.18 (d, J = 7.2 Hz, 2H), 1.10-1.05 (m, 12H)
1474[Figure (not displayed)]
MS (ESI) m/z 700.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 5.2 Hz, 1H), 8.60 (s, 1H), 8.43 (s, 1H), 7.59-7.57 (dd, J = 2.4, 10.8 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.36 (s, 2H), 4.19 (s, 2H), 3.65 (m, 4H), 4.44- 3.38 (m, 2H), 2.87 (bs, 4H), 1.77 (s, 3H)
1472[Figure (not displayed)]
MS (ESI) m/z 726.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.66 (bs, 1H), 8.45 (s, 1H), 7.59 (dd, J = 2.4, 9.2 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.38 (s, 2H), 4.21 (s, 2H), 3.75 (bs, 8H), 2.71 (s, 2H), 1.76 (s, 3H), 1.15 (s, 6H)
1476[Figure (not displayed)]
MS (ESI) m/z 710.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.90 (bs, 1H), 8.81 (d, J = 5.2 Hz, 1H), 8.61 (s, H), 8.47 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.63 (s, 2H), 4.59-4.47 (m, 6H), 4.38 (t, J = 4.4 Hz, 2H), 4.21 (d, J = 4.8 Hz, 2H), 2.70 (s, 1H), 1.81 (s, 3H), 1.09 (s, 6H), 1.07 (s, 6H)
1477[Figure (not displayed)]
MS (ESI) m/z 720.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.35 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.59 (dd, J = 2.40, 8.8 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.53 (bs, 1H), 4.39 (bs, 2H), 4.21 (bs, 2H), 3.74 (bs, 1H), 3.58 (bs, 2H), 3.09 (bs, 9H), 2.10 (bs, 4H), 1.77 (s, 3H)
1475[Figure (not displayed)]
MS (ESI) m/z 704.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 8.47 (s, 1H), 7.59 (dd, J = 9.2, 2.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.53 (bs, 4H),4.45-4.35 (m, 2H), 4.25-4.15 (m, 2H), 3.60- 3.45 (m, 1H), 3.20-2.70 (m, 4H), 2.60-2.40 (m, merged, 4H), 1.81 (s, 3H)
1479[Figure (not displayed)]
MS (ESI) m/z 663.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.37 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 4.4 Hz, 1H), 7.42 (bs, 1H), 7.36 (d, J = 8.8 Hz, 1H), 5.47 (d, J = 48.4 Hz, 1H), 4.93 (bs, 1H), 4.82 (bs, 1H), 4.39 (bs, 2H), 4.24 (bs, 2H), 3.68 (bs, 4H), 3.37-3.27 (m, 4H), 2.29-2.10 (m, 1H), 2.01-1.98 (m, 1H), 1.82-1.77 (m, 3H)
1480[Figure (not displayed)]
MS (ESI) m/z 691.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 7.61-7.58 (dd, J = 2.8, 8.8 Hz, 1H), 7.48-7.45 (dd, J = 10.8, 8.8 Hz, 2H), 7.37 (d, J = 9.2 Hz, 1H), 6.46 (m, 1H), 4.40 (t, 2H), 4.25 (bs, 2H), 3.07-2.97 (m, 8H), 2.22 (m, 2H), 2.06 (s, 3H), 1.79 (s, 3H)
1478[Figure (not displayed)]
MS (ESI) m/z 692.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.8 Hz, 1H), 8.62 (s, 1H), 8.47 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 6.41 (t, J = 53.6 Hz, 1H), 4.38-4.37 (m, 2H), 4.21 (s, 2H), 3.91 (bs, 6H), 3.17 (s, 4H), 3.03-2.81 (m, 2H), 1.79 (s, 3H)
1482[Figure (not displayed)]
MS (ESI) m/z 628.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.04 (bs, 1H), 9.07 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.77 (d, J = 9.2 Hz, 1H), 7.69 (t, J = 3.2 Hz, 1H), 7.54 (d, J = 4.4 Hz, 1H), 6.33 (s, 1H), 4.86 (s, 2H), 2.89-2.84 (m, 4H), 2.29-2.22 (m, 2H), 2.14 (s, 3H)
1483[Figure (not displayed)]
MS (ESI) m/z 753.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H), 9.87 (bs, 1H), 8.90 (d, J = 4.8 Hz, 1H), 8.76 (s, H), 8.55 (s, 1H), 7.63 (dd, J = 8.8, 2.4 Hz, 1H), 7.57 (d, J = 4.8 Hz, 1H), 7.44-7.37 (m, 2H), 4.73 (d, J = 46.0 Hz, 2H), 4.50-4.35 (m, 4H), 4.23 (s, 2H), 3.80-3.50 (m, 7H), 3.45-3.22 (m, 2H), 1.85 (s, 3H), 1.42 (s, 6H)
1481[Figure (not displayed)]
MS (ESI) m/z 630.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 8.57 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.77-7.75 (m, 1H), 7.69 (dd, J = 2.0, 6.8 Hz, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.86 (s, 2H), 2.53 (s, 1H), 2.17-2.15 (m, 3H), 2.08-2.06 (m, 2H), 2.01 (d, J = 5.6 Hz, 6H)
1485[Figure (not displayed)]
MS (ESI) m/z 639.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.34 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 9.2, 1H), 6.36 (t, J = 49.2 Hz, 1H), 4.40 (t, J = 4.8 Hz, 2H), 4.27-4.26 (m, 2H), 3.43 (bs, 4H), 2.73 (bs, 2H), 1.82 (s, 3H)
1486[Figure (not displayed)]
MS (ESI) m/z 769.56 [M + 1]+
1484[Figure (not displayed)]
MS (ESI) m/z 679.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.85 (bs, 1H), 8.96 (s, 1H), 8.82 (d, J = 4.8 Hz ,1H), 8.33 (s, 1H), 7.60 (dd, J = 2.4, 8.8 Hz, 2H), 7.47-7.43 (m, 1H), 7.36 (d, J = 8.8 Hz ,1H), 6.66-6.39 (m, 1H), 4.39 (t, J = 4.4 Hz ,2H), 4.25 (bs, 2H), 3.66-3.51 (m, 4H), 3.05 (d, J = 5.6 Hz, 4H), 2.19 (bs, 1H), 1.80 (s, 6H), 1.63-1.60 (m, 2H)
1488[Figure (not displayed)]
MS (ESI) m/z 719.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 10.12 (bs, 1H), 8.89 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.79 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.72-7.69 (m, 1H), 7.66 (d, J = 1.6 Hz, 1H), 7.62 (d, J = 4.8 Hz, 1H), 5.00-4.80 (m, 2H), 4.35 (bs, 2H), 3.82- 3.60 (m, 4H), 3.55 (s, 3H), 3.50-3.22 (m, 4H), 2.03 (s, 3H)
1489[Figure (not displayed)]
MS (ESI) m/z 698.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 9.2 Hz, 2H), 7.53 (d, J = 4.4 Hz, 1H), 4.83 (s, 2H), 3.59 (bs, 2H), 3.09 (bs, 8H), 5.19 (s, 5H), 1.82 (bs, 1H)
1487[Figure (not displayed)]
MS (ESI) m/z 737.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.44 (bs, 1H), 8.84-8.80 (m, 3H), 7.77 (d, J = 8.4 Hz, 1H), 7.71-7.66 (m, 2H), 7.61 (d, J = 4.8 Hz, 1H), 6.32 (t, J = 52.0 Hz, 1H), 4.83 (s, 2H), 3.75 (bs, 4H), 3.56 (bs, 3H), 2.95 (bs, 6H), 2.01 (s, 3H)
1491[Figure (not displayed)]
MS (ESI) m/z 680.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) d 8.76 (d, J = 4.8 Hz, 1H), 8.68 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 6.4 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 3.82 (t, J = 6.8 Hz, 2H), 3.33-3.25 (m, 5H), 2.92 (t, J = 6.8 Hz, 2H), 2.45 (s, 3H), 2.04 (s, 3H)
1492[Figure (not displayed)]
MS (ESI) m/z 633.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 8.73 (d, J = 4.8 Hz 1H), 8.59 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.40 (t, J = 50.8 Hz, 1H), 4.87 (s, 2H), 3.49 (bs, 4H), 3.12-2.77 (m, 5H), 2.17 (s, 3H)
1490[Figure (not displayed)]
MS (ESI) m/z 700.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.78 (s, 1H), 8.75 (d, J = 4.4 Hz, 1H), 8.64 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 9.6 Hz, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.39 (bs, 1H), 4.83 (s, 2H), 4.37-4.08 (m, 4H), 3.87 (bs, 4H), 3.26 (bs, 2H), 2.18 (bs, 4H), 2.10 (s, 3H)
1494[Figure (not displayed)]
MS (ESI) m/z 689.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 8.66 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.69-7.68 (m, 2H), 7.55 (d, J = 4.4 Hz, 1H), 4.82 (s, 2H), 4.30 (s, 1H), 3.06-3.01 (m, 7H), 2.06 (s, 3H), 1.86-1.83 (m, 4H), 1.25 (dd, J = 8.0 Hz, 5.6 Hz, 2H), 1.05 (dd, J = 7.2, 4.8 Hz, 2H)
1495[Figure (not displayed)]
MS (ESI) m/z 638.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79-8.74 (m, 2H), 8.65 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.54-4.53 (m, 1H), 3.58-3.55 (m, 2H), 3.20 (bs, 2H), 3.01 (s, 3H), 2.83-2.82 (m, 3H), 2.10 (bs, 7H)
1493[Figure (not displayed)]
MS (ESI) m/z 700.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.43-3.90 (m, 4H), 3.22-2.87 (m, 8H), 2.13 (s, 3H), 1.46 (s, 3H)
1497[Figure (not displayed)]
MS (ESI) m/z 694.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.69 (d, J = 6.8 Hz, 1H), 7.76-7.43 (m, 1H), 7.68 (dd, J = 2.0, 4.0 Hz, 1H), 7.54 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 3.73-3.70 (m, 2H), 3.27 (bs, 5H), 2.68-2.64 (m, 2H), 2.41 (s, 3H), 2.05 (s, 3H), 1.90 (t, J = 13.6 Hz, 2H)
1498[Figure (not displayed)]
MS (ESI) m/z 595.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.11 (bs, 1H), 9.73 (bs, 1H), 9.14 (s, 1H), 8.73 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.71-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 15.2 Hz, 1H), 7.20-7.10 (m, 1H), 4.88 (s, 2H), 4.16- 4.08 (m, 2H), 2.87 (s, 6H), 2.15 (s, 3H)
1496[Figure (not displayed)]
MS (ESI) m/z 690.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.7 Hz 1H), 8.72 (s, 1H), 8.69 (s, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.66-7.64 (m, 2H), 7.53 (d, J = 4.6 Hz, 1H), 4.83 (s, 2H), 4.60-4.58 (m, 1H), 3.18 (s, 3H), 3.10-3.00 (m, 1H), 2.27 (s, 3H), 1.60-1.57 (m, 1H), 1.30-1.24 (m, 5H), 0.87-0.67 (m, 8H)
1500[Figure (not displayed)]
MS (ESI) m/z 700.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 7.75 (d, J = 8 Hz, 1H), 7.68-7.66 (m, 2H), 7.51 (d, J = 4.8 Hz, 1H), 6.15 (tt, J = 4.0, 55.6 Hz, 1H), 4.79 (s, 2H), 4.53 (t, J = 7.2 Hz, 2H), 2.89 (d, J = 11.2 Hz, 2H), 2.77-2.67 (m, 4H), 2.21-2.16 (m, 4H), 2.03 (s, 3H), 1.81 (d, J = 11.6 Hz, 2H)
1501[Figure (not displayed)]
MS (ESI) m/z 783.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.81 (d ,J = 5.6 Hz, 2H), 8.75 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.71-7.68 (dd, J = 2.0, 10.4 Hz, 2H), 7.62 (d, J = 4.4 Hz, 1H), 4.82 (s, 2H), 4.32 (bs, 1H), 3.55 (s, 3H), 3.31 (bs, 2H), 3.10 (bs, 5H), 2.51 (bs, 2H), 1.97 (bs, 5H), 1.82-1.79 (m, 2H)
1499[Figure (not displayed)]
MS (ESI) m/z 672.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 9.90 (bs, 1H), 8.89 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.48 (t, J = 53.2 Hz, 1H), 5.21-5.02 (m, 2H), 4.82 (s, 2H), 4.53 (bs, 4H), 4.20-3.80 (m, 2H), 2.78-2.63 (m, 2H), 2.18 (s, 3H)
1503[Figure (not displayed)]
MS (ESI) m/z 718.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 8.76-8.74 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.79 (t, J = 74.8 Hz, 1H), 4.82 (s, 2H), 4.56 (bs, 1H), 4.23 (s, 2H), 3.65 (bs, 2H), 3.46 (bs, 2H), 3.26-3.19 (m, 2H), 3.11 (s, 3H), 2.26-2.08 (m, 2H), 2.04 (s, 5H)
1504 [Figure (not displayed)]
MS (ESI) m/z 744.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 2.0 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.73 (t, J = 75 Hz, 1H), 4.82 (s, 2H), 4.65 (bs, 1H), 4.21 (bs, 2H), 3.09 (s, 3H), 2.70-2.50 (m, 4H), 2.09 (bs, 7H), 1.33 (bs, 2H), 1.12 (bs, 2H)
1502[Figure (not displayed)]
MS (ESI) m/z 716.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.57 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.68-7.66 (m, 2H), 7.50 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.28-4.22 (m, 1H), 3.09 (s, 3H), 3.01 (d, J = 11.2 Hz, 2H), 2.75 (t, J = 14.4 Hz, 2H), 2.38-2.32 (m, 2H), 2.05 (s, 3H), 2.01- 1.85 (m, 4H), 1.77 (d, J = 11.6 Hz, 2H), 0.96 (t, J = 7.2 Hz, 3H)
1506[Figure (not displayed)]
MS (ESI) m/z 730.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.74 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 6.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.65-4.60 (m, 1H), 3.91-3.78 (m, 2H), 3.41-3.39 (m, 2H), 3.22 (s, 3H), 2.32-2.26 (m, 2H), 2.24- 2.08 (m, 5H), 1.84-1.79 (m, 3H), 1.51 (s, 6H)
1507 [Figure (not displayed)]
MS (ESI) m/z 734.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.66 (s, 1H), 7.76 (d, J = 5.2 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, H), 4.81 (s, 2H), 4.30-4.06 (m, 2H), 3.53-3.37 (m, 2H), 3.08 (s, 3H), 2.05 (s, 3H), 1.90-1.86 (m, 4H), 1.33 (s, 6H)
1505[Figure (not displayed)]
MS (ESI) m/z 671.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.68 (d, J = 1.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 3H), 3.38-3.28 (m, 4H), 3.11 (s, 9H), 2.02 (s, 3H), 1.97-1.91 (m, 2H), 1.89-1.83 (m, 2H)
1509[Figure (not displayed)]
MS (ESI) m/z 704.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (bs, 1H), 9.76 (bs, 1H), 8.84 (s,1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 6.71 (t, J = 75.6 Hz, 1H), 4.83 (s, 2H), 4.40-4.36 (m, 2H), 3.94 (t, J = 6.0 Hz, 2H), 3.74-3.71 (m, 2H), 3.60- 3.20 (m, 6H), 2.14 (s, 3H), 2.10-2.05 (m, 2H)
1510[Figure (not displayed)]
MS (ESI) m/z 716.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.66 (s, 1H), 7.75 (d, J = 9.1 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.68 (t, J = 75.9 Hz, 1H), 4.82 (s, 2H), 4.01 (bs, 2H), 3.40-2.80 (m, 8H), 2.08 (s, 3H), 1.05-0.65 (m, 4H)
1508[Figure (not displayed)]
MS (ESI) m/z, 684.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (bs, 4H), 4.68-4.62 (m, 2H), 3.60 (bs, 2H), 3.33 (bs, 2H), 3.11 (s, 3H), 2.24 (bs, 2H), 2.13 (bs, 2H), 2.09 (s, 3H), 1.33 (d, J = 6.8 Hz, 3H)
1512[Figure (not displayed)]
MS (ESI) m/z 745.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H), 10.01 (bs, 1H), 8.87 (d, J = 4.8 Hz, 1H ), 8.62 (s, 1H ), 8.60 (s, 1H ), 7.61 (dd, J = 8.8, 4.8 Hz, 1H), 7.54 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.5 Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 4.60 (s, 2H), 4.54 (s, 2H), 4.44-4.37 (m, 4H), 4.28-4.16 (m, 4H), 4.00-3.80 (m, 1H), 3.49 (s, 3H), 2.23-2.14 (m, 2H), 2.09-1.95 (m, 2H), 1.85-1.70 (m, 5H)
1513[Figure (not displayed)]
MS (ESI) m/z 724.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 8.40 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 6.79 (t, J = 75.2 Hz, 1H), 4.54-4.51 (m, 1H), 4.38 (d, J = 4.4 Hz, 2H), 4.28 (d, J = 4.4 Hz, 4H), 3.67-3.63 (m, 2H), 3.45 (bs, 2H), 3.25-3.22 (m, 2H), 3.09 (s, 3H), 2.21-2.15 (m, 2H), 2.08-2.05 (m, 2H), 1.71 (s, 3H)
1511[Figure (not displayed)]
MS (ESI) m/z 716.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 10.04 (bs, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz,1H), 8.64 (s,1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.60 (m, 2H), 7.52 (d, J = 4.4 Hz,1H), 6.71 (t, J = 75.2 Hz, 1H), 4.83 (s, 2H), 4.55-4.36 (m, 3H), 3.70- 3.40 (m, 5H), 3.16 (bs, 2H), 2.77 (bs, 2H), 2.50-2.35 (m, 2H), 2.14 (s, 3H)
1515[Figure (not displayed)]
MS (ESI) m/z 744.51 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 7.85 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 6.57 (t, J = 52 Hz, 1H), 4.38 (d, J = 4.8 Hz, 2H), 4.30-4.02 (m, 3H), 3.30-2.89 (m, 9H), 1.99 (bs, 2H), 1.82 (bs, 2H), 1.74 (s, 3H)
1516[Figure (not displayed)]
MS (ESI) m/z 753.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.66 (s, 1H), 9.81 (bs, 1H), 8.89 (d, J = 4.4 Hz, 1H), 8.75 (s, 1H), 8.57 (s, 1H), 7.59 (dd, J = 2.8, 9.2 Hz, 1H), 7.56 (d, J = 4.8 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 2.26 (s, 2H), 4.23 (s, 4H), 3.80 (bs, 6H), 3.61 (s, 3 H), 3.42 (bs, 2H), 1.81 (s, 3H), 1.53-1.48 (m, 6H)
1514[Figure (not displayed)]
MS (ESI) m/z 740.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.43 (s, 1H), 7.60 (dd, J = 9.2, 2.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.38-4.37 (m, 2H), 4.26 (bs, 2H), 4.19 (s,2H), 3.36 (bs, 2H), 3.05 (s, 3H), 1.83 (bs, 4H), 1.73 (s, 4H), 1.33 (s, 6H)
1519[Figure (not displayed)]
MS (ESI) m/z 680.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 8.75 (d, J = 4.8 Hz, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 2 Hz, 2H), 7.5 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.57 (bs, 2H), 4.34 (bs, 2H), 3.23 (d, J = 11.6 Hz, 2H), 3.19 (s, 1H), 3.11 (s, 3H), 2.31 (m, 2H), 2.21 (s, 3H), 2.10-2.03 (m, 5H)
1520[Figure (not displayed)]
MS (ESI) m/z 720.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.09 (bs, 1H), 8.77-8.75 (m, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 9.2 Hz, 2H), 7.55 (d, J = 4.4 Hz, 1H), 4.83 (s, 2H), 4.55 (bs, 1H), 3.70 (bs, 2H), 3.24 (bs, 4H), 3.11 (bs, 3H), 2.89 (bs, 2H), 2.15-2.11 (m, 7H)
1518[Figure (not displayed)]
MS (ESI) m/z 702.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.8 Hz, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.67 (s, 1H), 7.55 (d, J = 4.8 Hz, 1H), 6.53 (t, J = 50.0 Hz, 1H), 4.82 (bs, 2H), 4.57 (d, J = 2.4 Hz, 1H), 3.58 (bs, 2H), 3.36 (bs, 2H), 3.16 (s, 3H), 2.98 (bs, 1H), 2.24 (bs, 2H), 2.08 (bs, 5H), 1.35 (s, 3H)
1522[Figure (not displayed)]
MS (ESI) m/z 714.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 7.66 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.68 (t, J = 2.8 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.08 (t, J = 56.4 Hz, 1H), 4.81 (s, 2H), 4.09 (bs, 1H), 3.05 (bs, 5H), 2.92 (bs, 2H), 2.05 (s, 3H), 1.79-1.73 (m, 4H), 0.85-0.78 (m, 4H)
1523[Figure (not displayed)]
MS (ESI) m/z 680.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 6.4 Hz, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.4 Hz, 1H), 4.82 (s, 2H), 4.80-4.76 (m, 4H), 4.58 (bs, 1H), 4.37 (bs, 1H), 3.55 (d, J = 8.8 Hz, 2H), 3.12 (bs, 5H), 2.15- 2.10 (m, 5H), remainder of protons are merged in moisture peak
1521[Figure (not displayed)]
MS (ESI) m/z 784.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76-8.75 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.56 (dt, J = 47.2, 5.6 Hz, 2H), 4.59-4.57 (m, 1H), 3.68-3.55 (m, 2H), 3.21-3.19 (m, 4H), 3.11 (s, 3H), 2.21-2.05 (m, 9H)
1525[Figure (not displayed)]
MS (ESI) m/z 648.39 [M + 1]; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.76 (d, J = 4.4 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 1H), 7.55 (d, J = 4.8 Hz, 1H), 5.13 (bs, 1H), 4.81-4.67 (m, 6H), 3.97 (bs, 2H), 2.77 (bs, 2H), 2.10 (s, 3H), 0.85 (bs, 4H)
1526[Figure (not displayed)]
MS (ESI) m/z 704.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.69-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.73 bs, 4H), 3.00 (bs, 4H), 2.70-2.50 (m, merged, 1H), 2.20-2.07 (m, 1H), 2.08 (s, 3H), 1.03-1.08 (m, 2H)
1524[Figure (not displayed)]
MS (ESI) m/z 678.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (bs, 1H), 8.75.-8.74 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz ,1H), 7.68 (d, J = 8.8 Hz ,2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.64 (t, J = 8.4 Hz, 1H), 3.49 (s, 4H), 3.10 (s, 3H), 2.21-2.08 (m, 7H), 1.39 (s, 3H), 1.14 (bs, 2H), 0.81 (bs, 2H)
1528[Figure (not displayed)]
MS (ESI) m/z 625.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.66 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70-7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.60-4.45 (m, 1H), 4.05-3.95 (m, 2H), 3.65-3.40 (m, 2H), 3.11 (s, 3H), 2.06 (s, 3H), 2.00-1.85 (m, 2H), 1.78 (d, J = 10.8 Hz, 2H)
1529[Figure (not displayed)]
MS (ESI) m/z 696.48 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (bs, 1H), 8.76-8.74 (m, 2H), 8.65 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.75 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.72-4.66 (m, 2H), 3.65 (bs, 4H), 3.09 (s, 3H), 2.71 (s, 1H), 2.12-2.08 (m, 7H), 1.35 (bs, 2H), 1.16 (bs, 2H)
1527[Figure (not displayed)]
MS (ESI) m/z 664.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.05 (bs, 1H), 8.79 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.71-7.65 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.39 (d, J = 12.4 Hz, 2H), 3.19 (t, J = 12.0 Hz, 2H), 2.95-2.90 (m, 5H), 2.32-2.28 (m, 2H), 2.10 (s, 3H), 2.00-1.80 (m, 2H), 1.02-0.91 (m, 2H), 0.90-0.81 (m, 2H)
1531[Figure (not displayed)]
MS (ESI) m/z 714.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (bs, 1H), 10.53 (bs, 1H), 8.77-8.70 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 4.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.49 (t, J = 56.4 Hz, 1H), 4.82 (s, 2H), 4.57 (bs, 2H), 3.80-3.48 (m, 3H), 3.40- 3.20 (m, 2H), 3.16 (s, 4H), 3.01-2.70 (m, 2H), 2.02-2.15 (m, 2H), 2.06 (s, 3H), 1.80-1.65 (m, 2H)
1532[Figure (not displayed)]
MS (ESI) m/z 670.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.05 (bs, 1H), 8.76-8.70 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.96- 4.68 (m, 4H), 4.01-3.95 (m, 1H), 3.65- 3.28 (m, 3H), 3.22 (s, 3H), 2.82 (s, 3H), 2.80- 2.55 (m, 4H), 2.08 (s, 3H)
1530[Figure (not displayed)]
MS (ESI) m/z 732.40 [M + 1]+; 1H NMR (400 MHz, DMSO- d6) δ 8.76 (d, J = 4.8, 1H), 8.70 (s, 1H), 8.65 (s, 1H), 7.79-7.73 (m, 1H), 7.71- 7.65 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.32-4.20 (m, 1H), 3.12-3.10 (m, 5H), 2.81 (t, J = 11.2 Hz, 2H), 2.05 (s, 3H), 1.85-1.65 (m, 4H), 1.06-0.90 (m, 4H)
1534[Figure (not displayed)]
MS (ESI) m/z 597.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.79-8.75 (m, 2H), 7.75 (d, J = 8.0 Hz, 1H), 7.71-7.66 (m, 2H), 7.54 (d, J = 4.4 Hz, 1H), 5.00-4.97 (m, 1H), 4.88 (d, J = 18.4 Hz, 1H), 4.77-4.73 (m, 2H), 4.44 (bs, 1H), 3.89 (d, J = 12.0 Hz, 1H), 3.64 (d, J = 12.0 Hz, 1H), 3.57 (s, 3H), 2.13 (s, 3H)
1535[Figure (not displayed)]
MS (ESI) m/z 702.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.4 Hz, 2H), 8.66 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 6.51 (bs, 1H), 4.82 (s, 2H), 4.35 (bs, 1H), 3.66-3.51 (m, 6H), 3.06-2.97 (m, 2H), 2.16-2.02 (m, 7H), 1.13 (t, J = 6.8 Hz, 3H)
1533[Figure (not displayed)]
MS (ESI) m/z 698.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.19 (bs, 1H), 8.76-8.75 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 4.95-4.82 (m, 4H), 4.35-4.25 (m, 1H), 3.60-3.40 (m, 3H), 3.12 (s, 3H), 2.95-2.90 (m, 3H), 2.13- 1.72(m, 11H)
1537[Figure (not displayed)]
MS (ESI) m/z 768.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 5.2 Hz, 1H), 8.70 (s, 1H), 8.63 (s, 1H), 7.83 (bs, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.69 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.74-6.60 (m, 1H), 6.48 (bs, 1H), 4.81 (s, 2H), 4.5-4.25 (m, 2H), 4.15-4.05 (bs, 2H), 3.90 (s, 3H), 3.45-3.3 (bs, 2H), 3.09 (s, 3H), 2.2-2.13 (bs, 2H), 2.06 (s, 3H), 2.05-1.9 (bs, 2H)
1538[Figure (not displayed)]
MS (ESI) m/z 811.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.85 (d, J = 4.8 Hz 1H), 8.70 (s, 2H), 8.69 (s, 1H), 7.78- 7.69 (m, 3H), 7.63 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.32 (t, J = 11.6 Hz, 1H), 3.94-3.87 (m, 2H), 3.31 (bs, 2H), 3.10-3.07 (m, 5H), 2.59 (m, 1H), 1.96 (d, J = 9.3 Hz, 2H), 1.90-1.77 (m, 5H), 1.44 (s, 6H)
1536[Figure (not displayed)]
MS (ESI) m/z 768.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.90 (bs, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 4.8 Hz, 1H), 6.61 (bs, 1H), 4.82 (s, 2H), 4.53-4.24 (m, 5H), 3.92 (s, 3H), 3.53 (m, 2H), 3.09 (s, 5H), 2.00 (s, 5H)
1540[Figure (not displayed)]
MS (ESI) m/z 688.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80-8.74 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70-7.66 (m, 1H), 7.55 (d, J = 4.8 Hz, 1H), 6.47 (t, J = 58.0 Hz, 1H), 4.83 (s, 2H), 4.68 (bs, 1H), 3.70-3.40 (m, 4H), 3.16 (s, 3H), 3.08-2.75 (m, 2H), 2.08 (s, 3H), 2.05-1.75 (m, 4H)
1541[Figure (not displayed)]
MS (ESI) m/z 701.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (bs, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.69-8.66 (m, 2H), 7.76 (d, J = 8.8 Hz, 1H), 7.68 (t, J = 3.6 Hz, 2H), 7.55 (d, J = 4.4 Hz, 1H), 6.59 (bs, 1H), 4.81 (s, 2H), 3.72 (d, J = 6.0 Hz, 2H), 3.40 (bs, 4H), 3.33 (s, 3H), 3.11-2.99 (m, 2H), 2.06 (s, 3H), 1.79 (bs, 4H), 1.47 (bs, 1H)
1539[Figure (not displayed)]
MS (ESI) m/z 833.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.88 (bs, 1H), 8.84-8.83 (m, 2H), 8.73 (s, 1H), 7.77 (d, J = 4.4 Hz, 1H), 7.76-7.69 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 6.73-6.46 (tt, J = 54.4, 4.4 Hz, 1H), 4.82 (s, 2H), 4.49 (dt, J = 14.8, 4.0 Hz, 2H), 4.36-4.30 (m, 1H), 3.36 (bs, 2H), 3.10 (s, 5H), 2.66-2.63 (m, 2H), 2.05-1.77 (m, 7H)
1543[Figure (not displayed)]
MS (ESI) m/z 707.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.35 (bs, 1H), 8.38 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.36 (s, 1H), 7.61 (dd, J = 2.4, 8.8 Hz, 1H), 7.59 (d, J = 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 5.46-5.45 (m, 1H), 4.39 (bs, 2H), 4.24 (bs, 2H), 3.92 (m, 1H), 3.60-3.58 (m, 2H), 3.08- 3.05 (m, 8H), 2.14-1.90 (m, 2H), 1.79-1.77 (m, 3H)
1544[Figure (not displayed)]
MS (ESI) m/z 714.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 2H), 8.64 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.69 (t, J = 8.8 Hz, 2H), 7.54 (d, J = 4.8 Hz, 1H), 6.49 (bs, 1H), 4.82 (s, 2H), 4.49 (s, 1H), 3.75 (bs, 8H), 2.97 (s, 2H), 2.08 (bs, 5H), 1.81 (s, 1H), 1.68 (d, J = 12.8 Hz, 2H)
1542[Figure (not displayed)]
MS (ESI) m/z 674.40 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.72-7.69 (m, 2H), 7.57 (d, J = 4.4 Hz, 1H), 6.42-6.15 (m, 1H), 4.90-4.80 (m, 3H), 4.51-4.46 (m, 1H), 3.87-3.84 (m, 2H), 3.68-3.61 (m, 3H), 3.58-3.37 (m, 2H), 3.25-3.17 (m, 2H), 2.87 (bs, 2H), 2.17 (s, 3H)
1546[Figure (not displayed)]
MS (ESI) m/z 811.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.43 (s, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.74 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.61 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.29 (t, J = 23.2 Hz, 1H), 3.22 (q, J = 10.0 Hz, 2H), 3.09 (s, 3H), 3.04 (d, J = 19.2 Hz, 10H), 1.92 (d, J = 8.0 Hz, 5H), 1.78 (d, J = 9.6 Hz, 2H)
1547[Figure (not displayed)]
MS (ESI) m/z 809.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.52 (s, 1H), 8.79 (t, J = 8.0 Hz, 2H), 8.73 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 2 Hz, 2H), 7.60 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.31 (t, J = 21.2 Hz, 1H), 3.29-3.22 (m, 4H), 3.10 (bs, 5H), 2.50 (s, 1H), 1.94 (d, J = 11.7 Hz, 5H), 1.78 (s, 2H), 1.29 (d, J = 3.8 Hz, 2H), 1.26-1.14 (m, 2H)
1545[Figure (not displayed)]
MS (ESI) m/z 714.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 at 353.1 K) 68.15 (s, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.68 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.67-7.64 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.86-4.80 (m, 2H), 4.08-4.05 (m, 1H), 3.09 (s, 3H), 2.98 (m, 3H), 2.18 (s, 3H), 2.06- 2.01 (m, 1H), 1.67 (t, J = 18.4 Hz, 3H), 1.38- 1.26 (m, 4H)
1549[Figure (not displayed)]
MS (ESI) m/z 859.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.93 (d, J = 4.8 Hz, 1H), 8.56 (s, 1H), 8.25 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.77-7.55 (m, 1H), 7.70-7.63 (m, 4H), 7.55-7.51 (m, 1H), 7.45 (d, J = 7.6 Hz, 1H) 4.82 (s, 2H), 4.29 (bs, 1H), 3.31 (bs, 2H), 3.08 (bs, 5H), 2.67 (s, 3H), 2.63-2.58 (m, 2H), 1.94-1.88 (m, 2H). 1.83 (s, 3H), 1.79-1.76 (m, 2H)
1550[Figure (not displayed)]
MS (ESI) m/z 881.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.28 (bs, 1H), 8.94 (d, J = 5.2 Hz, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.24- 8.19 (m, 1H), 7.77-7.75 (m, 1H), 7.70-7.68 (m, 2H), 7.66 (d, J = 4.8 Hz, 1H), 7.61-7.56 (m, 1H), 7.48-7.40 (m, 1H), 4.80 (s, 2H), 4.37-4.26 (m, 1H), 3.37 (bs, 2H), 3.12-3.10 (m, 2H), 3.07 (s, 3H), 2.66-2.63 (m, 2H), 1.99-1.88 (m, 2H), 1.85-1.74 (m, 5H)
1548[Figure (not displayed)]
MS (ESI) m/z 845.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.09 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.67 (s, 1H), 8.45 (s, 1H), 8.15 (d, J = 7.2 Hz, 2H), 7.78-7.74 (m, 2H), 7.69-7.66 (m, 4H), 7.61 (d, J = 4.8 Hz, 1H), 4.80 (s, 2H), 4.31 (bs, 1H), 3.28 (bs, 2H), 3.09-3.06 (m, 5H), 2.58-2.50 (m, 2H), 1.94 (d, J = 11.2 Hz, 2H), 1.87 (s, 3H), 1.79 (d, 10.4 Hz, 2H)
1553[Figure (not displayed)]
MS (ESI) m/z 730.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 8.56 (s, 1H), 7.60-7.73 (m, 1H), 7.67-7.66 (m, 2H), 7.51 (d, J = 4.8 Hz, 1H), 6.14-5.56 (m, 1H), 4.82 (s, 2H), 4.59-4.55 (m, 2H), 4.48 (t, J = 6.4 Hz, 2H), 4.34-4.31 (m, 2H), 4.26-4.21 (m, 1H), 3.14-3.03 (m, 4H), 2.87 (t, J = 12.4 Hz, 1H), 2.07 (s, 3H), 1.76 (d, J = 12.0 Hz, 2H), 1.56-1.48 (m, 2H)
1554[Figure (not displayed)]
MS (ESI) m/z 757.34 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.79 (d, J = 4.8 7.71 (d, J = 2.0 Hz, 1H), 7.68 (bs, 1H), 7.58 (d, J = 4.4 Hz, 1H), 6.29 (t, J = 61.2 Hz, 1H), 4.86 (s, 2H), 4.44 (bs, 2H), 4.04 (bs, 4H), 3.25 (bs, 2H), 2.16 (bs, 4H), 2.10 (bs, 3H)
1551[Figure (not displayed)]
MS (ESI) m/z 859.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.93 (d, J = 4.8 Hz, 1H), 8.56 (s, 1H), 8.25 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.77-7.55 (m, 1H), 7.70-7.63 (m, 4H), 7.55-7.51 (m, 1H), 7.45 (d, J = 7.6 Hz, 1H) 4.82 (s, 2H), 4.29 (bs, 1H), 3.31 (bs, 2H), 3.08 (bs, 5H), 2.67 (s, 3H), 2.63-2.58 (m, 2H), 1.94-1.88 (m, 2H). 1.83 (s, 3H), 1.79-1.76 (m, 2H)
1556[Figure (not displayed)]
MS (ESI) m/z 700.34 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.77-8.74 (m 2H), 8.65 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.70-7.66 (dd, J = 2.0, 10.4 Hz, 2H), 7.55 (d, J = 4.4 Hz, 1H), 6.54 (bs, 1H), 4.82 (s, 2H), 4.42 (s, 1H), 4.19 (bs, 1H), 3.86-3.59 (bs, 4H), 3.16- 2.74 (bs, 4H), 2.11 (s, 5H), 1.97-1.78 (bs, 2H)
1557[Figure (not displayed)]
MS (ESI) m/z 702.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 10.03 (bs, Hz, 1H), 8.59 (s, 1H), 7.77 (s, 1H), 7.75 (s, 1H), CI 1H), 8.80-8.68 (m, 3H), 7.74-7.63 (m, 3H), 7.59 (d, J = 5.2 Hz, 1H), 6.53 (t, J = 54.4 Hz, 1H), 5.90-5.40 (m, 1H), 4.48 (bs, 1H), 3.81-3.41 (m, 4H), 3.38-3.10 (m, 2H), 3.09 (s, 3H), 2.40-1.95 (m, 7H), 1.47 (t, J = 6.8 Hz, 3H)
1555[Figure (not displayed)]
MS (ESI) m/z 764.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.13 (bs, 1H), 8.77 (s, 1H), 8.75 (d, J = 7.2 Hz, 1H), 8.65 (s, 1H), 7.76 (s, 1H), 7.70 (d, J = 2.0 Hz, 2H), 7.67-7.54 (m, 6H), 4.82 (s, 2H), 4.56-4.22 (m, 5H), 3.01 (s, 5H), 2.97-2.87 (m, 2H), 2.09 (s, 5H)
1559[Figure (not displayed)]
MS (ESI) m/z 695.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.22 (bs, 1H), 8.78 (d, J = 4.7 Hz, 1H), 8.65 (s, 1H), 8.00-7.99 (m, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.70-7.66 (m, 4H), 7.56 (d, J = 4.7 Hz, 1H), 6.43 (t, J = 53.4 Hz, 1H), 4.90 (s, 2H), 4.23 (bs, 2H), 3.41 (bs, 2H), 2.66 (bs, 3H), 2.19 (s, 3H)
1560[Figure (not displayed)]
MS (ESI) m/z 703.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 9.44 (bs, 1H), 8.73 (s, 1H), 8.68 (d, J = 4.8 Hz, 1H), 8.48 (s, 1H), 7.74-7.72 (m, 1H), 7.66-7.64 (m, 2H), 7.48 (d, J = 4.8 Hz, 1H), 6.45 (b, 1H), 4.80 (s, 2H), 4.49 (bs, 1H), 3.35 (s, 4H), 3.08 (s, 3H), 2.50- 2.47 (m, 2H), 2.08 (bs, 2H), 1.99 (s, 5H)
1558[Figure (not displayed)]
MS (ESI) m/z 707.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.70-7.68 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 7.49-7.44 (m, 2H), 7.36 (bs, 1H), 6.42 (tt, J = 52.4, 7.4 Hz, 1H), 4.90 (s, 2H), 4.38 (bs, 2H), 3.48 (bs, 2H), 3.24 (bs, 2H), 2.86 (bs, 2H), 2.16 (s, 3H)
1562[Figure (not displayed)]
MS (ESI) m/z 722.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.86 (bs, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.46 (s, 1H), 7.61-7.58 (m, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.41-7.36 (m, 2H), 4.50 (m, 1H), 4.41 (bs, 2H), 4.21 (bs, 2H), 3.65- 3.37 (m, 4H), 3.06 (s, 3H), 2.62 (s, 3H), 2.25 (m, 2H), 2.00 (m, 2H), 1.79-1.69 (m, 8H)
1563[Figure (not displayed)]
MS (ESI) m/z 722.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.41 (bs, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.42-7.40 (m, 2H), 7.36 (d, J = 9.2 Hz, 1H), 4.53 (bs, 1H), 4.38 (bs, 2H), 4.21 (bs, 2H), 3.84 (bs, 4H), 3.08 (s, 3H), 3.54 (bs, 2H), 2.70 (s, 3H)), 1.99 (bs, 2H), 1.82 (bs, 5H), 1.76 (bs, 3H)
1561[Figure (not displayed)]
MS (ESI) m/z 757.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.81-8.78 (m, 3H), 7.77 (d, J = 8.4, 1H), 7.72-7.67 (m, 2H), 7.62 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.78 (t, J = 6.8 Hz, 4H), 4.60 (bs, 1H), 4.36 (bs, 1H), 3.58 (bs, 2H), 3.53 (s, 3H), 3.12 (s, 3H), 3.05 (d, J = 14.0 Hz, 2H), 2.14 (bs, 4H), 1.99 (s, 3H)
1565[Figure (not displayed)]
MS (ESI) m/z 708.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70-7.66 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.66-4.36 (m, 5H), 3.91-3.78 (m, 4H), 2.95 (bs, 3H), 2.13 (s, 3H)
1566[Figure (not displayed)]
MS (ESI) m/z 828.47 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.90 (d, J = 4.8 Hz, 1H), 8.71 (d, J = 4.4 Hz, 1H), 8.65 (s, 1H), 8.60 (s, 1H), 8.27-8.18 (m, 2H), 7.77-7.53 (m, 4H), 7.49 (d, J = 5.6 Hz, 1H), 6.66-6.29 (m, 1H), 4.82 (s, 2H), 4.60-4.45 (m, 1H), 3.50-3.15 (m, 6H), 3.09 (s, 3H), 2.30-1.80 (m, 7H)
1564[Figure (not displayed)]
MS (ESI) m/z 668.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.67-7.70 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 5.45 (d, J = 56.8 Hz, 1H), 4.83 (s, 2H), 4.54- 4.29 (m, 5H), 3.52 (bs, 2H), 3.15-3.09 (m, 2H), 2.19-2.09 (m, 5H), 1.60-1.52 (m, 2H)
1569[Figure (not displayed)]
MS (ESI) m/z 618.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 614.24 (bs, 1H), 13.11 (bs, 1H), 9.17 (s, 1H), 8.79 (d, J = 4.80 Hz, 1H), 8.67 (s, 1H), 8.52 (d, J = 7.20 Hz, 2H), 7.76 (d, J = 8.00 Hz, 1H), 7.71-7.68 (m, 2H), 7.53 (d, J = 4.80 Hz, 1H), 7.38 (d, J = 7.20 Hz, 2H), 4.89 (s, 2H), 3.69 (s, 3H), 2.23 (s, 3H)
1571[Figure (not displayed)]
MS (ESI) m/z 665.43 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.35 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.55 (t, J = 53.2 Hz, 1H), 4.40 (d, J = 4.4 Hz, 2H), 4.26 (s, 2H), 3.87 (bs, 1H), 3.47-3.24 (m, 4H), 2.00- 1.89 (m, 4H),1.78 (s, 3H), 1.74-1.67 (m, 2H)
1568[Figure (not displayed)]
MS (ESI) m/z 636.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.18 (bs, 1H), 8.84 (s, 1H), 8.75 (d, J = 4.8 Hz,1H), 8.65 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.65 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.38 (m, 2H), 3.79 (m, 2H,), 3.49 (m, 4H), 3.03 (m, 1H), 2.14 (s, 3H), 0.93 (m, 4H)
1573[Figure (not displayed)]
MS (ESI) m/z 685.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.61 (s, 1H), 7.77-7.75 (m, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.4 Hz, 1H), 6.60 (bs, 1H), 6.41 (s, 1H), 4.86 (s, 2H), 3.99- 3.58 (m, 2H), 3.03-2.76 (m, 4H), 2.54 (s, 3H), 2.29-2.14 (m, 5H), 1.77-1.75 (m, 1H)
1574[Figure (not displayed)]
MS (ESI) m/z 659.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.60 (s, 1H), 7.76 (d, J = 18.4 Hz, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 4.8 Hz, 2H), 6.55 (t, J = 54.4 Hz, 1H), 4.87 (s, 2H), 3.60- 2.87 (m, 7H), 2.17 (s, 3H), 2.04-1.73 (m, 4H)
1572[Figure (not displayed)]
MS (ESI) m/z 709.45 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.63 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.70 (dd, J = 6.4 Hz, 2.0 Hz, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.89 (s, 2H), 3.78-3.56 (m, 3H), II s ' 3.28-3.19 (m, 2H), 3.00-2.79 (m, 2H), 2.08 (s, 3H), 1.98-1.85 (m, 4H)
1576[Figure (not displayed)]
MS (ESI) m/z 714.55 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.68-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.81-3.38 (m, 5H), 3.08 (s, 3H), 2.82-2.70 (m, 2H), 2.43-2.33 (m, 2H), 2.06 (s, 3H),1.68-1.53 (m, 7H)
1577[Figure (not displayed)]
MS (ESI) m/z 714.49 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.68-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.81-3.38 (m, 5H), 3.08 (s, 3H), 2.82-2.70 (m, 2H), 2.43-2.33 (m, 2H), 2.06 (s, 3H), 1.68-1.53 (m, 7H)
1575[Figure (not displayed)]
MS (ESI) m/z 728.08 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.68-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 3.81-3.38 (m, 5H), 3.08 (s, 3H), 2.82-2.70 (m, 2H), 2.43-2.33 (m, 2H), 2.06 (s, 3H), 1.68-1.53 (m, 7H)
1579[Figure (not displayed)]
MS (ESI) m/z 760.64 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.17 (s, 1H), 8.66 (s, 1H), 7.76-7.74 (m, 1H), 7.70-7.68 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 6.43-4.15 (m, 1H), 4.81 (s, 2H), 4.30 (bs, 1H), 3.54 (bs, 4H), 3.08 (s, 3H), 2.05 (bs, 7H), 1.83- 1.67 (m, 6H), 1.17 (bs, 3H)
1581[Figure (not displayed)]
MS (ESI) m/z 702.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74-8.70 (m, 2H), 8.37 (s, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.67-7.64 (m, 2H), 7.44 (d, J = 4.4 Hz, 1H), 6.16 (t, J = 55.6 Hz, 1H), 4.89-4.84 (m, 3H), 3.081 (bs, 4H), 2.80-2.72 (m, 2H), 2.33 (bs, 3H), 2.07-1.98 (m, 4H), 1.90 (bs, 3H), 1.75-1.71 (m, 1H), 1.41 (t, J = 7.2 Hz, 1H)
1578[Figure (not displayed)]
MS (ESI) m/z 771.57 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.82 (d, J = 4.4 Hz, 2H), 8.78 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.72-7.67 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.77-4.75 (m, 4H), 4.44-4.35 (m, 2H), 3.76-3.59 (m, 3H), 3.54 (s, 3H), 3.28- 3.19 (m, 1H), 3.02 (bs, 2H), 2.15 (s, 4H), 1.99 (s, 3H), 1.15 (t, J = 6.8 Hz, 3H)
1583[Figure (not displayed)]
MS (ESI) m/z 744.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.66 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.69-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.26-4.23 (m, 1H), 3.12-3.09 (m, 4H), 2.93 (bs, 3H), 2.57-2.52 (m, 2H), 2.06 (s, 3H), 1.89 (bs, 4H), 1.75-1.72 (m, 7H), 1.22 (bs, 2H)
1584[Figure (not displayed)]
MS (ESI) m/z 724.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.76-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.74-7.56 (m, 3H), 3.52-3.49 (m, 2H), 3.32-3.26 (m, 4H), 3.11 (s, 3H), 2.26-2.21 (m, 2H), 2.10 (s, 3H), 2.03-1.91 (m, 8H)
1582[Figure (not displayed)]
MS (ESI) m/z 778.66 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.73 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70-7.67 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.58 (bs, 2H), 4.24 (bs, 2H), 3.11 (s, 3H), 2.94-2.67 (m, 6H), 2.32-2.08 (m, 9H)
1586[Figure (not displayed)]
MS (ESI) m/z 748.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.8 Hz, 1H), 8.72 (s, 1H), 8.70 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.70-7.62 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.84 (s, 2H), 4.48-4.30 (m, 1H), 3.40-2.85 (m, 9H), 2.20-1.75 (m, 7H), 1.20 (s, 6H)
1587[Figure (not displayed)]
MS (ESI) m/z 746.54 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.13 (bs, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.65 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.68-7.67 (m, 2H), 7.54 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.26 (bs, 1H), 3.09 (s, 3H), 3.04 (d, J = 10.8 Hz, 2H), 2.70-2.50 (merged, 2H), 2.10-2.00 (m, 5H), 1.88-1.81 (m, 4H), 0.97 (s, 2H), 0.74 (s, 2H)
1585[Figure (not displayed)]
MS (ESI) m/z 722.42 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.71 (s, 1H), 8.66 (s, 1H), 7.76-7.74 (m, 1H), 7.69-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.81 (s, 2H), 4.29-4.27 (m, 1H), 3.44 (bs, 2H), 3.17-3.09 (m, 5H), 2.66 (bs, 2H), 2.05 (s, 3H), 1.94 (d, J = 10.4 Hz, 2H),1.80 (d, J = 10.8 Hz, 2H)
1589[Figure (not displayed)]
MS (ESI) m/z 791.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 9.72 (bs, 1H), 8.81-8.78 (m, 3H), 7.77 (d, J = 8.4 Hz, 1H), 7.72-7.67 (m, 2H), 7.62 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.59 (bs, 1H), 3.82-3.45 (m, 6H), 3.30-2.95 (m, 9H), 2.20-2.14 (m, 4H), 1.99 (s, 3H)
1590[Figure (not displayed)]
MS (ESI) m/z 807.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.80 (d, J = 5.2 Hz 1H), 8.78 (s, 1H), 8.75 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.70 (dd, J = 10.4 Hz, 2 Hz, 2H), 7.62 (d, J = 4.8 Hz, 1H), 6.45 (t, J = 54.8 Hz, 1H), 4.82 (s, 2H), 4.50 (d, J = 6.8 Hz, 2H), 4.45 (d, J = 6.8 Hz, 2H), 4.34-4.29 (m, 1H), 3.55 (s, 3H), 3.11 (s, 3H), 2.91 (d, J = 10.8 Hz, 2H), 2.60-2.53 (m, 2H),1.96-1.85 (m, 7H)
1588[Figure (not displayed)]
MS (ESI) m/z 760.61 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 9.09 (bs, 1H), 8.80-8.70 (m, 2H), 8.65 (s, 1H), 7.75 (d, J = 8.40 Hz, 1H), 7.71-7.63 (m, 2H), 7.54 (d, J = 4.00 Hz, 1H), 4.82 (s, 2H), 4.56 (bs, 1H), 3.70- 3.50 (m, 4H), 3.20-3.20 (merged, 2H), 3.11 (s, 3H), 2.41-2.20 (m, 6H), 2.18-1.94 (m, 7H)
1592[Figure (not displayed)]
MS (ESI) m/z 714.10 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.09 (bs, 1H), 8.75-8.74 (m, 2H), 8.64 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.69-7.67 (m, 2H), 7.53 (d, J = 4.8 Hz, 1H), 4.82 (s, 2H), 4.39 (bs, 2H), 4.01 (bs, 1H), 3.66 (bs, 1H), 3.20-2.95 (m, 5H), 2.72-2.66 (m, 2H), 2.08 (bs, 5H), 1.90-1.60 (m, 4H)
1593[Figure (not displayed)]
MS (ESI) m/z 851.58 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.03 (bs, 1H), 8.87 (d, J = 4.80 Hz, 1H), 8.84 (s, 1H), 8.73 (s, 1H), 7.77 (d, J = 9.20 Hz, 1H), 7.71-7.69 (m, 2H), 7.65 (d, J = 4.80 Hz, 1H), 5.06 (q, J = 9.60 Hz, 2H), 4.82 (s, 2H), 4.32-4.29 (m, 1H), 3.33 (bs, 2H), 3.09 (bs, 5H), 2.58 (bs, 2H), 1.96 (bs, 2H), 1.92 (s, 3H), 1.80 (d, J = 11.2 Hz, 2H)
1591[Figure (not displayed)]
MS (ESI) m/z 857.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 5.2 Hz, 1H), 8.81 (s, 1H), 8.75 (s, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.71-7.69 (m, 2H), 7.64 (d, J = 4.8 Hz, 1H), 6.73-6.58 (m, 1H), 6.15-5.87 (m, 1H), 4.82 (s, 2H), 4.59-4.55 (m, 2H), 4.52-4.47 (m, 4H), 4.35-4.22 (m, 4H), 3.16-3.04 (m, 3H), 2.86 (m, 1H), 1.92 (s, 3H), 1.76 (d, J = 11.2 Hz, 2H), 1.56-1.48 (m, 2H)
1595[Figure (not displayed)]
MS (ESI) m/z 847.0 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.06 (bs, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.83 (s, 1H), 8.75 (s, 1H), 7.78 (d, J = 8.80 Hz, 1H), 7.71 (bs, 2H), 7.65 (d, J = 4.80 Hz, 1H), 5.04 (q, J = 9.60 Hz, 2H), 4.83 (s, 2H), 4.59 (bs, 1H), 3.77 (bs, 4H), 3.37 (bs, 2H), 3.11 (s, 3H), 2.26 (bs, 2H), 2.02 (bs, 2H), 1.95 (s, 3H), 1.76 (t, J = 17.6 Hz, 3H)
1596[Figure (not displayed)]
MS (ESI) m/z 701.0 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6 with D2O) 6 8.68 (s, 1H), 8.67 (s, 1H), 8.39 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.65-7.63 (m, 1H), 7.57 (d, J = 1.6 Hz, 1H), 7.41 (d, J = 4.8 Hz, 1H), 4.73 (s 2H), 4.55-4.49 (m, 1H), 3.80-3.72 (m, 2H), 3.62-3.57 (m, 2H), 3.28 (t, J = 11.6 Hz, 2H), 3.09 (s, 1H), 2.53 (bs, 1H), 2.32-2.20 (m, 2H), 2.06 (bs, 6H), 1.74 (t, J = 19.6 Hz, 3H)
1594[Figure (not displayed)]
MS (ESI) m/z 705.48 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.67 (s, 1H), 8.45 (s, 1H), 7.72 (d, J = 8.00 Hz, 1H), 7.65 (d, J = 8.40 Hz, 1H), 7.61 (bs, 1H), 7.44 (d, J = 2.40 Hz, 1H), 4.76 (s, 2H), 4.32 (t, J = 12.00 Hz, 1H), 3.49 (d, J = 8.80 Hz, 2H), 3.18 (d, J = 10.80 Hz, 2H), 3.07 (s, 3H), 2.73 (t, J = 11.2 Hz, 2H), 2.02 (s, 3H), 1.96 (d, J = 13.2 Hz, 2H), 1.85 (d, J = 10.8 Hz, 2H)
1598[Figure (not displayed)]
MS (ESI) m/z 758.69 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.94 (bs, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69-7.67 (m, 2H), 7.55 (d, J = 4.4 Hz, 1H), 6.43 (bs, 1H), 4.82 (s, 2H), 4.53 (bs, 1H), 3.79 (bs, 4H), 3.39-3.35 (m, 2H), 3.11 (s, 3H), 2.41 (bs, 2H), 2.32-2.26 (m, 2H), 2.09 (s, 7H), 1.86-1.82 (m, 1H), 1.65-1.60 (m, 1H)
1599[Figure (not displayed)]
MS (ESI) m/z 638.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79-8.74 (m, 2H), 8.65 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.54-4.53 (m, 1H), 3.58-3.55 (m, 2H), 3.20 (bs, 2H), 3.01 (s, 3H), 2.83-2.82 (m, 3H), 2.10 (bs, 7H)
1597[Figure (not displayed)]
MS (ESI) m/z 833.52 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.08 (bs, 1H), 8.86-8.84 (m, 2H), 7.79-7.769 (m, 1H), 7.71 (t, J = 2.0 Hz, 2H), 7.66 (d, J = 5.2 Hz, 1H), 6.51 (bs, 1H), 5.08-5.01 (m, 2H), 4.83 (s, 2H), 4.52 (bs, 1H), 3.94 (bs, 2H), 3.41 (bs, 4H), 3.21 (s, 3H), 2.15 (bs, 2H), 2.07 (s, 5H)
1601[Figure (not displayed)]
MS (ESI) m/z 805.69 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.47 (bs, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.78 (bs, 2H), 7.79 (d, J = 11.6 Hz, 1H), 7.70 (bs, 1H), 7.68 (bs, 1H), 7.63 (d, J = 4.80 Hz, 1H), 4.82 (s, 2H), 4.20 (bs, 1H), 3.65 (g, J = 6.80 Hz, 2H), 3.54 (s, 3H), 2.93-2.90 (m, 2H), 2.69-2.66 (m, 4H), 2.42-2.32 (m, 3H), 1.94 (s, 3H), 1.92-1.89 (m, 4H) 1.11 (t, J = 6.8 Hz, 3H)
1602[Figure (not displayed)]
MS (ESI) m/z 773.67 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 9.72 (bs, 1H), 8.81-8.78 (m, 3H), 7.77 (d, J = 8.36 Hz, 1H), 7.72-7.67 (m, 2H), 7.62 (d, J = 4.80 Hz, 1H), 5.33-5.14 (dm, 1H), 4.83 (s, 2H), 4.63-4.55 (m, 1H), 4.03-3.97 (m, 1H), 3.60-3.50 (merged, 3H), 3.11 (s, 3H), 3.09-3.02 (m, 2H), 2.76-2.50 (m, 6H), 2.12-2.07 (m, 4H), 1.99 (s, 3H)
1600[Figure (not displayed)]
MS (ESI) m/z 678.56 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.12 (bs, 1H), 8.83-8.73 (m, 3H), 8.66 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.70-7.68 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.40 (bs, 1H), 3.71-3.57 (m, 4H), 3.40-3.20 (merged, 2H), 2.85 (bs, 1H), 2.18- 2.00 (m, 7H), 1.14 (t, J = 6.4 Hz, 3H), 0.98-0.79 (m, 4H)
1604[Figure (not displayed)]
MS (ESI) m/z 793.67 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.73 (bs, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.71-7.69 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.61 (bs, 1H), 3.84 (bs, 1H), 3.69-3.65 (m, 2H), 3.11 (s, 3H), 2.02-1.91 (m, 6H), 1.76 (bs, 4H), 1.38 (t, J = 14.4 Hz, 3H)
1605[Figure (not displayed)]
MS (ESI) m/z 793.67 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.73 (bs, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.71-7.69 (m, 2H), 7.63 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.61 (bs, 1H), 3.84 (bs, 1H), 3.69-3.65 (m, 2H), 3.11 (s, 3H), 2.02-1.91 (m, 6H), 1.76 (bs, 4H), 1.38 (t, J = 14.4 Hz, 3H)
1603[Figure (not displayed)]
MS (ESI) m/z 833.74 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 9.86 (bs, 1H), 8.80-8.78 (d, J = 8.80 Hz, 2H), 8.68 (s, 1H), 7.80-7.67 (m, 4H), 4.88 (s, 2H), 4.54 (bs, 1H), 3.66-3.38 (m, 4H), 3.33-3.27 (m, 2H), 3.09 (s, 3H), 2.40-2.25 (m, 2H), 2.12 (s, 3H), 2.10-1.99 (m, 2H), 1.76 (t, J = 19.2 Hz, 3H)
1607[Figure (not displayed)]
MS (ESI) m/z 829.71 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.81 (d, J = 4.8 Hz, 1H), 8.78 (d, J = 3.0 Hz, 2H), 7.77 (d, J = 8.16 Hz, 1H), 7.70-7.68 (m, 2H), 7.49 (d, J = 6.36 Hz, 1H), 6.56 (tt, J = 4.16 Hz, J = 88.08 Hz, 1H), 4.82 (s, 2H), 4.22-4.16 (m, 1H), 3.65 (d, J = 6.88 Hz, 2H), 3.55 (s, 3H) 3.04-2.94 (m, 4H), 2.49-2.41 (m, 2H), 1.99-1.89 (m, 5H), 1.78 (d, J = 10.68 Hz, 2H), 1.11 (t, J = 6.72 Hz, 3H)
1608[Figure (not displayed)]
MS (ESI) m/z 871.79 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.78 (s, 1H), 8.72 (s, 1H), 7.77 (d, J = 8.16 Hz, 1H), 7.71-7.69 (m, 2H), 7.64 (d, J = 4.84 Hz, 1H), 6.58 (tt, J = 52.56 Hz, 5.4 Hz, 1H), 5.25-5.20 (m, 1H), 4.98-4.92 (m, 4H), 4.82 (s, 2H), 4.24 (bs, 1H), 3.95 (bs, 2H), 3.68-3.62 (m, 2H), 3.50-3.10 (m, 4H), 2.01-1.97 (m, 2H), 1.90 (s, 3H), 1.86 (bs, 2H), 1.12 (t, J = 6.8 Hz, 3H)
1606[Figure (not displayed)]
MS (ESI) m/z 821.52 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.80 (d, J = 4.84 Hz, 1H), 8.78 (d, J = 2.6 Hz, 2H), 7.77 (d, J = 8.31 Hz, 1H), 7.71-7.67 (m, 2H), 7.62 (d, J = 4.80 Hz, 1H), 4.76 (s, 2H), 4.60-4.57 (m, 1H), 3.85-3.58 (m, 4H), 3.49 (s, 3H), 3.32 (t, J = 12 Hz, 2H), 3.10 (s, 3H), 2.32-2.02 (m, 4H), 1.98 (s, 3H), 1.80-1.70 (m, 3H)
1610[Figure (not displayed)]
MS (ESI) m/z 881.27 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 8.81 (d, J = 4.84 Hz, 1H), 8.77 (s, 1H), 8.76 (s, 1H), 7.77 (d, J = 8.36 Hz, 1H), 7.72-7.67 (m, 2H), 7.62 (d, J = 4.84 Hz, 1H), 5.20-5.16 (m, 1H), 4.97- 4.89 (m, 4H), 4.82 (s, 2H), 4.75-4.70 (m, 1H), 4.61-4.57 (m, 1H), 3.54-3.51 (m, 2H), 3.54-3.43 (m, 3H), 3.11 (s, 3H), 3.08-3.06 (m, 2H), 2.87- 2.83 (m, 2H), 2.11-2.08 (m, 4H), 1.95 (s, 3H)
1611[Figure (not displayed)]
MS (ESI) m/z 902.74 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.89 (d, J = 4.80 Hz, 1H), 8.72 (d, J = 4.40 Hz, 1H), 8.64 (s, 1H), 8.61 (s, 1H), 8.27-8.25 (m, 1H), 8.22-8.18 (m, 1H), 7.77-7.73 (m, 2H), 7.71-7.69 (m, 2H), 7.65 (d, J = 4.80 Hz, 1H), 4.83 (s, 2H), 4.75- 4.70 (m, 1H), 4.58 (bs, 1H), 3.67 (bs, 3H), 3.54 (d, J = 10.80 Hz, 2H), 3.42-3.38 (m, 1H), 2.86- 2.84 (m, 2H), 2.85 (bs, 2H), 2.45-2.40 (m, 2H), 2.08 (bs, 4H), 1.95 (s, 3H)
1609[Figure (not displayed)]
MS (ESI) m/z 892.75 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 8.91 (d, J = 4.4 Hz, 1H), 8.72 (d, J = 3.6 Hz, 1H), 8.65 (s, 1H), 8.60 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.21 (t, J = 7.6 Hz, 1H), 7.77-7.75 (m, 2H), 7.70-7.66 (m, 3H), 6.58 (t, J = 52.8 Hz, 1H), 4.82 (s, 2H), 4.23 (bs, 1H), 3.62 (d, J = 7.2 Hz, 2H), 3.16- 3.12 (m, 4H), 2.53 (s, 2H), 2.01 (bs, 2H), 1.90- 1.84 (m, 5H), 1.09 (t, J = 6.4 Hz, 3H)
1617[Figure (not displayed)]
MS (ESI) m/z 730.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D2O) 6 8.67 (bs, 2H), 7.95 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.28 (s, 1H), 7.21 (bs, 2H), 6.28 (m, J = 53.6 Hz, 1H), 4.30 (bs, 2H), 4.21-4.00 (m, 3H), 3.29-3.19 (m, 4H), 2.99 (s, 3H), 2.80 (bs, 2H), 2.03 (bs, 2H), 1.86 (bs, 2H), 1.64 (s, 3H)
1618[Figure (not displayed)]
MS (ESI) m/z 791.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.47 (s, 1H), 9.72 (bs, 1H), 8.81-8.78 (m, 3H), 7.77 (d, J = 8.4 Hz, 1H), 7.72-7.67 (m, 2H), 7.62 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.59 (bs, 1H), 3.82-3.45 (m, 6H), 3.30-2.95 (m, 9H), 2.20-2.14 (m, 4H), 1.99 (s, 3H)
1616[Figure (not displayed)]
MS (ESI) m/z 786.58 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D2O) 6 8.77 (d, J = 4.40 Hz, 1H), 8.68 (s, 1H), 8.19 (d, J = 9.60 Hz, 1H), 7.52 (dd, J = 2.2, 8.8 Hz, 1H), 7.35-7.26 (m, 3H), 6.24 (t, J = 54.4 Hz, 1H), 4.33-4.17 (m, 10H), 3.21 (bs, 3H), 3.03 (s, 3H), 2.70 (bs, 1H), 2.58 (bs, 1H), 1.97 (bs, 2H), 1.82 (bs, 2H), 1.55 (s, 3H), 1.28 (t, J = 6.8 Hz, 6H)
1621[Figure (not displayed)]
LCMS: 603.6 [M + H]+; 1H NMR (400 MHz, Methanol-d4) 6 8.31 (s, 1H), 7.54 (dd, J = 8.9, 2.6 Hz, 1H), 7.41 (s, 1H), 7.36-7.25 (m, 2H), 4.46 (t, J = 5.1 Hz, 2H), 4.34 (t, J = 5.1 Hz, 2H), 3.13 (s, 6H), 2.89 (s, 3H), 2.83 (s, 3H), 2.24 (s, 3H)
1622[Figure (not displayed)]
LCMS (ESI) m/z 658.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 7.69 (tt, J = 8.5, 6.6 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48-7.43 (m, 2H), 7.40-7.32 (m, 3H), 4.43 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 4.9 Hz, 2H), 2.81 (s, 3H), 2.69 (s, 3H), 1.88 (s, 3H)
1620[Figure (not displayed)]
MS (ESI) m/z 726.41 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.0 Hz, 1H), 8.57 (s, 1H), 8.34 (s, 1H), 7.58 (d, J = 7.2, 1H), 7.39-7.33 (m, 3H), 4.37 (bs, 2H), 4.25 (bs, 3H), 3.91 (s, 3H), 3.3; 2-3.30 (m, 2H), 3.07-2.72 (m, 5H), 2.44-2.32 (m, 2H), 1.93-1.74 (bs, 4H), 1.69 (s, 3H)
1624[Figure (not displayed)]
LCMS (ESI) m/z 662.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.8 Hz, 1H), 8.46 (s, 1H), 7.57 (dd, J = 9.0, 2.6 Hz, 1H), 7.44 (d, J = 4.8 Hz, 1H), 7.39-7.32 (m, 2H), 4.98-4.74 (m, 2H), 4.40 (t, J = 5.1 Hz, 2H), 4.29 (s, 1H), 4.21 (t, J = 5.1 Hz, 2H), 3.64 (s, 3H), 3.56 (s, 1H), 3.47 (s, 1H), 3.31 (s, 2H), 2.63 (s, 3H), 1.86 (s, 3H)
1625[Figure (not displayed)]
MS (ESI) m/z 805.29 [M + 1]+
1623[Figure (not displayed)]
LCMS (ESI) m/z 644.1 [M + 1]+; 1H NMR (400 MHz, Chloroform-d) δ 8.48 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42-7.37 (m, 2H), 4.42 (d, J = 5.3 Hz, 2H), 4.33 (s, 1H), 4.30 (s, 1H), 4.25 (d, J = 5.0 Hz, 2H), 3.61 (d, J = 12.2 Hz, 2H), 3.44 (d, J = 13.6 Hz, 4H), 3.24 (d, J = 11.0 Hz, 1H), 2.92 (d, J = 4.4 Hz, 3H), 2.73 (s, 3H), 2.66 (s, 4H), 1.98 (s, 3H)
1627[Figure (not displayed)]
MS (ESI) m/z 602.29 [M + 1]+
1628[Figure (not displayed)]
MS (ESI) m/z 608.3 [M + 1]+
1626[Figure (not displayed)]
LCMS (ESI) m/z 599.2 [M + 1]+
1630[Figure (not displayed)]
MS (ESI) m/z 618.09 [M + 1]+
1631[Figure (not displayed)]
1629[Figure (not displayed)]
1633[Figure (not displayed)]
LCMS (ESI) m/z 608.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.70 (d, J = 4.7 Hz, 2H), 8.63 (s, 1H), 8.47 (s, 2H), 7.72 (dd, J = 8.1, 0.8 Hz, 1H), 7.68-7.61 (m, 2H), 7.50 (d, J = 4.8 Hz, 1H), 4.77 (s, 2H), 4.54 (s, 4H), 4.20 (t, J = 6.2 Hz, 4H), 2.06 (s, 3H), 1.20 (s, 1H)
1634[Figure (not displayed)]
MS (ESI) m/z 678.5 [M + 1]+
1632[Figure (not displayed)]
LCMS (ESI) m/z 469.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77-8.71 (m, 2H), 8.66 (s, 1H), 7.75 (dd, J = 8.1, 0.8 Hz, 1H), 7.72-7.64 (m, 2H), 7.54 (d, J = 4.9 Hz, 1H), 4.81 (s, 2H), 4.63 (s, 2H), 4.53 (s, 2H), 4.44 (s, 2H), 4.39 (s, 2H), 3.36 (s, 4H), 2.73-2.62 (m, 1H), 2.10 (s, 3H)
1636[Figure (not displayed)]
MS (ESI) m/z 619.45 [M + 1]+
1637[Figure (not displayed)]
MS (ESI) m/z 638.39 [M + 1]+
1635[Figure (not displayed)]
MS (ESI) m/z 688.48 [M + 1]+
1639[Figure (not displayed)]
MS (ESI) m/z 706.46 [M + 1]+
1640[Figure (not displayed)]
1638[Figure (not displayed)]
MS (ESI) m/z 670.50 [M + 1]+
1642[Figure (not displayed)]
MS (ESI) m/z 710.46 [M + 1]+
1643[Figure (not displayed)]
MS (ESI) m/z 706.47 [M + 1]+
1641[Figure (not displayed)]
MS (ESI) m/z 706.55 [M + 1]
1645[Figure (not displayed)]
MS (ESI) m/z 628.46 [M + 1]+
1646[Figure (not displayed)]
MS (ESI) m/z 668.45 [M + 1]+
1644[Figure (not displayed)]
MS (ESI) m/z 690.47 [M + 1]+
1648[Figure (not displayed)]
LCMS: 2.01 Min, 777.3 [M + H]+
1649[Figure (not displayed)]
MS (ESI) m/z = 706.48 [M + 1]+
1647[Figure (not displayed)]
MS (ESI) m/z 706.46 [M + 1]+
1651[Figure (not displayed)]
1652[Figure (not displayed)]
1650[Figure (not displayed)]
MS (ESI) m/z 720.47 [M + 1]+
1654[Figure (not displayed)]
MS (ESI) m/z, 690.46 [M + 1]+
1655[Figure (not displayed)]
MS (ESI) m/z 704.57 [M + 1]+
1653[Figure (not displayed)]
MS (ESI) m/z 670.43 [M + 1]+
1657[Figure (not displayed)]
1658[Figure (not displayed)]
1656[Figure (not displayed)]
1660[Figure (not displayed)]
1661[Figure (not displayed)]
1659[Figure (not displayed)]
1663[Figure (not displayed)]
MS (ESI) m/z 688.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 4.8 Hz, 1H), 8.70 (s, 1H), 8.61 (s, 1H), 7.74-7.71 (m, 1H), 7.67-7.63 (m, 2H), 7.52 (d, J = 4.8 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H), 6.80 (tt, J = 52.4, 3.5 Hz, 1H), 4.78 (s, 2H), 4.55-4.40 (m, 1H), 4.02 (td, J = 14.3, 3.9 Hz, 2H), 3.69-3.60 (m, 4H), 3.25(s, 3H), 2.32-2.18 (m, 2H), 2.10-2.01 (m, 2H), 2.00 (s, 3H).
1664[Figure (not displayed)]
1662[Figure (not displayed)]
MS (ESI) m/z 708.54 [M + 1]+
1666[Figure (not displayed)]
1672[Figure (not displayed)]
1676[Figure (not displayed)]
1665[Figure (not displayed)]
MS (ESI) m/z = 714.5 [M + 1]+
1669[Figure (not displayed)]
1670[Figure (not displayed)]
1667[Figure (not displayed)]
1668[Figure (not displayed)]
1673[Figure (not displayed)]
1671[Figure (not displayed)]
1675[Figure (not displayed)]
1677[Figure (not displayed)]
1674[Figure (not displayed)]
1678[Figure (not displayed)]
1679[Figure (not displayed)]
1680[Figure (not displayed)]
1681[Figure (not displayed)]
1683[Figure (not displayed)]
1687[Figure (not displayed)]
1684[Figure (not displayed)]
1686[Figure (not displayed)]
1690[Figure (not displayed)]
MS (ESI) m/z 728.47 [M + 1]+
1682[Figure (not displayed)]
1685[Figure (not displayed)]
1688[Figure (not displayed)]
MS (ESI) m/z 720.47 [M + 1]+
1689[Figure (not displayed)]
MS (ESI) m/z 714.45 [M + 1]+
1691[Figure (not displayed)]
MS (ESI) m/z 714.55 [M + 1]+
1697[Figure (not displayed)]
1700[Figure (not displayed)]
1693[Figure (not displayed)]
1694[Figure (not displayed)]
1702[Figure (not displayed)]
1692[Figure (not displayed)]
1696[Figure (not displayed)]
1695[Figure (not displayed)]
1699[Figure (not displayed)]
1701[Figure (not displayed)]
1698[Figure (not displayed)]
1706[Figure (not displayed)]
MS (ESI) m/z 878.31 [M + 1]+
1703 [Figure (not displayed)]
MS (ESI) m/z 815.32 [M + 1]+
1704[Figure (not displayed)]
MS (ESI) m/z 857.25 [M + 1]+
1705[Figure (not displayed)]
MS (ESI) m/z 878.28 [M + 1]+
1707[Figure (not displayed)]
1711[Figure (not displayed)]
1708[Figure (not displayed)]
1709[Figure (not displayed)]
1710[Figure (not displayed)]
1714[Figure (not displayed)]
1712[Figure (not displayed)]
1713[Figure (not displayed)]
1715[Figure (not displayed)]
1716[Figure (not displayed)]
1717[Figure (not displayed)]
MS (ESI) m/z 762.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.75 (s, 1H), 8.65 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.71-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 7.26 (s, 1H), 4.83 (s, 2H), 4.68-4.55 (m, 1H), 4.22 (d, J = 13.7 Hz, 1H), 3.99-3.71 (m, 7H), 3.20 (s, 3H), 2.70-2.61 (m, 2H), 2.42- 2.30 (m, 2H), 2.18-2.00 (m, 5H)
1721[Figure (not displayed)]
1719[Figure (not displayed)]
1723[Figure (not displayed)]
MS (ESI) m/z 726.28 [M + 1]+
1718[Figure (not displayed)]
1720[Figure (not displayed)]
1725[Figure (not displayed)]
MS (ESI) m/z 732.19 [M + 1]+
1722[Figure (not displayed)]
MS (ESI) m/z 817.25 [M + 1]+
1724[Figure (not displayed)]
MS (ESI) m/z 732.18 [M + 1]+
1728[Figure (not displayed)]
MS (ESI) m/z 809.32 [M + 1]+
1726[Figure (not displayed)]
MS (ESI) m/z 823.30 [M + 1]+
1727[Figure (not displayed)]
MS (ESI) m/z 732.19 [M + 1]+
1729[Figure (not displayed)]
MS (ESI) m/z 823.3 [M + 1]+
1732[Figure (not displayed)]
MS (ESI) m/z 837.31 [M + 1]+
1730[Figure (not displayed)]
MS (ESI) m/z 746.28 [M + 1]+
1731[Figure (not displayed)]
MS (ESI) m/z 823.27 [M + 1]+
1735[Figure (not displayed)]
MS (ESI) m/z 796.33 [M + 1]+
1733[Figure (not displayed)]
MS (ESI) m/z 785.26 [M + 1]+
1734[Figure (not displayed)]
MS (ESI) m/z 839.26 [M + 1]+
1738[Figure (not displayed)]
MS (ESI) m/z 848.33 [M + 1]+
1736[Figure (not displayed)]
MS (ESI) m/z 810.23 [M + 1]+
1737[Figure (not displayed)]
MS (ESI) m/z 838.32 [M + 1]+
1741[Figure (not displayed)]
MS (ESI) m/z 834.32 [M + 1]+
1739[Figure (not displayed)]
MS (ESI) m/z 847.32 [M + 1]+
1740[Figure (not displayed)]
MS (ESI) m/z 834.36 [M + 1]+
1744[Figure (not displayed)]
MS (ESI) m/z 825.21 [M + 1]+
1742[Figure (not displayed)]
MS (ESI) m/z 834.31 [M + 1]+
1743[Figure (not displayed)]
MS (ESI) m/z 788.18 [M + 1]+
1747[Figure (not displayed)]
MS (ESI) m/z 813.29 [M + 1]+
1745[Figure (not displayed)]
MS (ESI) m/z 821.25 [M + 1]+
1746[Figure (not displayed)]
MS (ESI) m/z 799.24 [M + 1]+
1750[Figure (not displayed)]
MS (ESI) m/z 813.22 [M + 1]+
1748[Figure (not displayed)]
MS (ESI) m/z 811.27 [M + 1]+
1749[Figure (not displayed)]
MS (ESI) m/z 797.29 [M + 1]+
1753[Figure (not displayed)]
MS (ESI) m/z 785.32 [M + 1]+
1751[Figure (not displayed)]
MS (ESI) m/z 771.31 [M + 1]+
1752[Figure (not displayed)]
MS (ESI) m/z 708.23 [M + 1]+
1756[Figure (not displayed)]
MS (ESI) m/z 821.28 [M + 1]+
1754[Figure (not displayed)]
MS (ESI) m/z 799.34 [M + 1]+
1755[Figure (not displayed)]
MS (ESI) m/z 821.31 [M + 1]+
1757[Figure (not displayed)]
MS (ESI) m/z 835.45 [M + 1]+
1758[Figure (not displayed)]
MS (ESI) m/z 758.28 [M + 1]+
1759[Figure (not displayed)]
MS (ESI) m/z 835.26 [M + 1]+
1760[Figure (not displayed)]
MS (ESI) m/z 849.43 [M + 1]+
1761[Figure (not displayed)]
LCMS (ESI) m/z 821.4 [M + 1]+
1762[Figure (not displayed)]
LCMS (ESI) m/z 863.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 9.53 (d, J = 9.3 Hz, 1H), 8.83 (d, J = 4.9 Hz, 1H), 8.78 (d, J = 6.8 Hz, 2H), 7.78 (dd, J = 8.3, 0.5 Hz, 1H), 7.77-7.66 (m, 2H), 7.64 (d, J = 4.9 Hz, 1H), 6.73 (t, J = 21 Hz, 1H), 5.21 (tt, J = 7.8, 6.2 Hz, 1H), 5.00-4.89 (m, 4H), 4.84 (s, 2H), 4.82- 4.74 (m, 1H), 4.60 (p, J = 8.0 Hz, 1H), 3.94 (q, J = 7.8 Hz, 1H), 3.58 (d, J = 11.8 Hz, 2H), 3.13 (s, 3H), 3.05 (s, 2H), 2.78-2.68 (m, 1H), 2.72 (s, 1H), 2.17-2.06 (m, 4H), 1.97 (s, 3H)
1763[Figure (not displayed)]
LCMS (ESI) m/z 884.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.90 (d, J = 4.9 Hz, 1H), 8.72 (ddd, J = 4.7, 1.7, 1.0 Hz, 1H), 8.63 (d, J = 13.4 Hz, 2H), 8.27 (dt, J = 7.9, 1.1 Hz, 1H), 8.24-8.16 (m, 1H), 7.80-7.67 (m, 4H), 7.66 (d, J = 4.8 Hz, 1H), 6.72 (t, J = 76 Hz, 1H), 4.83 (s, 2H), 4.78 (dt, J = 7.3, 3.8 Hz, 1H), 4.58 (d, J = 5.8 Hz, 1H), 3.93 (q, J = 7.6 Hz, 1H), 3.56 (d, J = 11.8 Hz, 2H), 3.04 (s, 1H), 2.72 (dd, J = 14.6, 7.1 Hz, 2H), 2.09 (s, 3H), 1.97 (s, 3H)
1764[Figure (not displayed)]
LCMS (ESI) m/z 884.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.95-8.89 (m, 2H), 8.82 (d, J = 4.9 Hz, 1H), 8.65 (s, 1H), 8.47 (s, 1H), 8.07 76 Hz, 1H) 4.81-4.71 (m, 2H), 4.55 (p, J = 8.0 Hz, 1H), 3.93-3.85 (m, 1H), 3.53 (d, J = 11.7 Hz, 2H), 3.01 (s, 1H), 2.77-2.63 (m, 2H), 2.07 (s, 3H), 1.90 (s, 2H), 1.90 (d, J = 16.7 Hz, OH)
1765[Figure (not displayed)]
LCMS (ESI) m/z 884.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.24 (dd, J = 2.5, 0.8 Hz, 1H), 8.89 (dd, J = 4.8, 1.6 Hz, 1H), 8.81 (d, J = 4.9 Hz, 1H), 8.63 (s, 1H), 8.50 (ddd, J = 8.2, 2.4, 1.6 Hz, 1H), 8.46 (s, 1H), 7.76-7.64 (m, 3H), 7.64-7.57 (m, 2H), 6.69 (t, J = 76 Hz, 1H), 4.76 (d, J = 10.9 Hz, 3H), 4.55 (t, J = 8.0 Hz, 1H), 3.94-3.85 (m, 1H), 3.52 (s, 1H), 3.08 (s, 3H), 3.02 (s, 1H), 2.74-2.64 (m, 2H), 2.08 (s, 4H), 1.88 (s, 3H)
1766[Figure (not displayed)]
MS (ESI) m/z 758.34 [M + 1]+
1767[Figure (not displayed)]
MS (ESI) m/z 835.33 [M + 1]+
1768[Figure (not displayed)]
MS (ESI) m/z 877.29 [M + 1]+
1769[Figure (not displayed)]
MS (ESI) m/z 898.4 [M + 1]+
1770[Figure (not displayed)]
MS (ESI) m/z 898.26 [M + 1]+
1771[Figure (not displayed)]
MS (ESI) m/z 898.29 [M + 1]+
1772[Figure (not displayed)]
MS (ESI) m/z 839.28 [M + 1]+
1773[Figure (not displayed)]
MS (ESI) m/z 902.19 [M + 1]+
1774[Figure (not displayed)]
MS (ESI) m/z 902.23 [M + 1]+
1775[Figure (not displayed)]
MS (ESI) m/z 776.35 [M + 1]+
1776[Figure (not displayed)]
MS (ESI) m/z 853.3 [M + 1]+
1777[Figure (not displayed)]
MS (ESI) m/z 819.33 [M + 1]+
1778[Figure (not displayed)]
MS (ESI) m/z 895.27 [M + 1]+
1779[Figure (not displayed)]
MS (ESI) m/z 916.3 [M + 1]+
1780[Figure (not displayed)]
MS (ESI) m/z 916.27 [M + 1]+
1781[Figure (not displayed)]
MS (ESI) m/z 916.27 [M + 1]+
1782[Figure (not displayed)]
MS (ESI) m/z 762.31 [M + 1]+
1783[Figure (not displayed)]
MS (ESI) m/z 839.26 [M + 1]+
1784[Figure (not displayed)]
MS (ESI) m/z 776.29 [M + 1]+
1785[Figure (not displayed)]
MS (ESI) m/z 853.37 [M + 1]+
1786[Figure (not displayed)]
MS (ESI) m/z 760.31 [M + 1]+
1787[Figure (not displayed)]
MS (ESI) m/z 837.35 [M + 1]+
1788[Figure (not displayed)]
MS (ESI) m/z 851.42 [M + 1]+
1789[Figure (not displayed)]
MS (ESI) m/z 851.41 [M + 1]+
1790[Figure (not displayed)]
MS (ESI) m/z 865.46 [M + 1]+
1791[Figure (not displayed)]
MS (ESI) m/z 815.24 [M + 1]+
1792[Figure (not displayed)]
MS (ESI) m/z 836.27 [M + 1]+
1793[Figure (not displayed)]
MS (ESI) m/z 836.3 [M + 1]+
1794[Figure (not displayed)]
MS (ESI) m/z 836.33 [M + 1]+
1795[Figure (not displayed)]
MS (ESI) m/z 710.25 [M + 1]+
1796[Figure (not displayed)]
MS (ESI) m/z 787.34 [M + 1]+
1797[Figure (not displayed)]
MS (ESI) m/z 829.34 [M + 1]+
1798[Figure (not displayed)]
MS (ESI) m/z 850.31 [M + 1]+
1799[Figure (not displayed)]
MS (ESI) m/z 850.34 [M + 1]+
1800[Figure (not displayed)]
MS (ESI) m/z 850.25 [M + 1]+
1801[Figure (not displayed)]
MS (ESI) m/z 710.28 [M + 1]+
1802[Figure (not displayed)]
MS (ESI) m/z 787.28 [M + 1]+
1803[Figure (not displayed)]
MS (ESI) m/z 801.44 [M + 1]+
1804[Figure (not displayed)]
MS (ESI) m/z 797.32 [M + 1]+
1805[Figure (not displayed)]
MS (ESI) m/z 811.3 [M + 1]+
1806[Figure (not displayed)]
MS (ESI) m/z 770.31 [M + 1]+
1807[Figure (not displayed)]
MS (ESI) m/z 805.28 [M + 1]+
1808[Figure (not displayed)]
MS (ESI) m/z 819.358 [M + 1]+
1809[Figure (not displayed)]
MS (ESI) m/z 817.27 [M + 1]+
1810[Figure (not displayed)]
MS (ESI) m/z 831.26 [M + 1]+
1811[Figure (not displayed)]
MS (ESI) m/z 833.22 [M + 1]+
1812[Figure (not displayed)]
MS (ESI) m/z 833.39 [M + 1]+
1813[Figure (not displayed)]
MS (ESI) m/z 624.2 [M + 1]+
1814[Figure (not displayed)]
MS (ESI) m/z 843.32 [M + 1]+
1815[Figure (not displayed)]
MS (ESI) m/z 787.34 [M + 1]+
1816[Figure (not displayed)]
MS (ESI) m/z 850.31 [M + 1]+
1817[Figure (not displayed)]
MS (ESI) m/z 809.22 [M + 1]+
1818[Figure (not displayed)]
MS (ESI) m/z 845.26 [M + 1]+
1819[Figure (not displayed)]
MS (ESI) m/z 841.17 [M + 1]+
1820[Figure (not displayed)]
MS (ESI) m/z 817.25 [M + 1]+
1821[Figure (not displayed)]
MS (ESI) m/z 863.33 [M + 1]+
1822[Figure (not displayed)]
MS (ESI) m/z 863.38 [M + 1]+
1823[Figure (not displayed)]
MS (ESI) m/z 861.36 [M + 1]+
1824[Figure (not displayed)]
MS (ESI) m/z 895.39 [M + 1]+
1825[Figure (not displayed)]
MS (ESI) m/z 816.24 [M + 1]+
1826[Figure (not displayed)]
MS (ESI) m/z 830.3 [M + 1]+
1827[Figure (not displayed)]
MS (ESI) m/z 858.28 [M + 1]+
1828[Figure (not displayed)]
MS (ESI) m/z 833.34 [M + 1]+
1829[Figure (not displayed)]
MS (ESI) m/z 854.26 [M + 1]+
1830[Figure (not displayed)]
MS (ESI) m/z 854.26 [M + 1]+
1831[Figure (not displayed)]
MS (ESI) m/z 854.22 [M + 1]+
1832[Figure (not displayed)]
MS (ESI) m/z 868.26 [M + 1]+
1833[Figure (not displayed)]
MS (ESI) m/z 867.24 [M + 1]+
1834[Figure (not displayed)]
MS (ESI) m/z 811.4 [M + 1]+
1835[Figure (not displayed)]
MS (ESI) m/z 825.41 [M + 1]+
1836[Figure (not displayed)]
MS (ESI) m/z 819.33 [M + 1]+
1837[Figure (not displayed)]
MS (ESI) m/z 847.35 [M + 1]+
1838[Figure (not displayed)]
MS (ESI) m/z 868.26 [M + 1]+
1839[Figure (not displayed)]
MS (ESI) m/z 868.26 [M + 1]+
1840[Figure (not displayed)]
MS (ESI) m/z 868.29 [M + 1]+
1840[Figure (not displayed)]
MS (ESI) m/z 700.33 [M + 1]+
1842[Figure (not displayed)]
MS (ESI) m/z 777.26 [M + 1]+
1843[Figure (not displayed)]
MS (ESI) m/z 794.33 [M + 1]+
1844[Figure (not displayed)]
MS (ESI) m/z 796.44 [M + 1]+
1845[Figure (not displayed)]
MS (ESI) m/z 841.34 [M + 1]+
1846[Figure (not displayed)]
MS (ESI) m/z 805.38 [M + 1]+
1847[Figure (not displayed)]
MS (ESI) m/z 819.34 [M + 1]+
1848[Figure (not displayed)]
MS (ESI) m/z 823.3 [M + 1]+
1849[Figure (not displayed)]
MS (ESI) m/z 835.36 [M + 1]+
1850[Figure (not displayed)]
MS (ESI) m/z 730.34 [M + 1]+
1851[Figure (not displayed)]
MS (ESI) m/z 807.33 [M + 1]+
1852[Figure (not displayed)]
MS (ESI) m/z 730.36 [M + 1]+
1853[Figure (not displayed)]
MS (ESI) m/z 807.18 [M + 1]+
1854[Figure (not displayed)]
MS (ESI) m/z 746.16 [M + 1]+
1855[Figure (not displayed)]
MS (ESI) m/z 823.36 [M + 1]+
1856[Figure (not displayed)]
MS (ESI) m/z 730.37 [M + 1]+
1857[Figure (not displayed)]
MS (ESI) m/z 807.4 [M + 1]+
1858[Figure (not displayed)]
MS (ESI) m/z 807.3 [M + 1]+
1589[Figure (not displayed)]
MS (ESI) m/z 728.3 [M + 1]+
1860[Figure (not displayed)]
MS (ESI) m/z 805.32 [M + 1]+
1861[Figure (not displayed)]
MS (ESI) m/z 746.31 [M + 1]+
1862[Figure (not displayed)]
MS (ESI) m/z 823.39 [M + 1]+
1863[Figure (not displayed)]
MS (ESI) m/z 704.27 [M + 1]+
1864[Figure (not displayed)]
MS (ESI) m/z 781.26 [M + 1]+
1865[Figure (not displayed)]
MS (ESI) m/z 795.37 [M + 1]+
1866[Figure (not displayed)]
MS (ESI) m/z 718.34 [M + 1]+
1867[Figure (not displayed)]
MS (ESI) m/z 795.35 [M + 1]+
1868[Figure (not displayed)]
MS (ESI) m/z 809.44 [M + 1]+
1869[Figure (not displayed)]
MS (ESI) m/z 720.3 [M + 1]+
1870[Figure (not displayed)]
MS (ESI) m/z 797.35 [M + 1]+
1871[Figure (not displayed)]
MS (ESI) m/z 811.4 [M + 1]+
1872[Figure (not displayed)]
MS (ESI) m/z 728.26 [M + 1]+
1873[Figure (not displayed)]
MS (ESI) m/z 805.26 [M + 1]+
1874[Figure (not displayed)]
MS (ESI) m/z 819.46 [M + 1]+
1875[Figure (not displayed)]
MS (ESI) m/z 819.33 [M + 1]+
1876[Figure (not displayed)]
MS (ESI) m/z 746.28 [M + 1]+
1877[Figure (not displayed)]
MS (ESI) m/z 823.3 [M + 1]+
1878[Figure (not displayed)]
MS (ESI) m/z 746.34 [M + 1]+
1879[Figure (not displayed)]
MS (ESI) m/z 823.33 [M + 1]+
1880[Figure (not displayed)]
MS (ESI) m/z 756.29 [M + 1]+
1881[Figure (not displayed)]
MS (ESI) m/z 833.32 [M + 1]+
1882[Figure (not displayed)]
MS (ESI) m/z 738.34 [M + 1]+
1883[Figure (not displayed)]
MS (ESI) m/z 815.4 [M + 1]+
1884[Figure (not displayed)]
MS (ESI) m/z 692.31 [M + 1]+
1885[Figure (not displayed)]
MS (ESI) m/z 772.35 [M + 1]+
1886[Figure (not displayed)]
MS (ESI) m/z 849.4 [M + 1]+
1887[Figure (not displayed)]
MS (ESI) m/z 758.28 [M + 1]+
1888[Figure (not displayed)]
MS (ESI) m/z 835.26 [M + 1]+
1889[Figure (not displayed)]
MS (ESI) m/z 754.34 [M + 1]+
1890[Figure (not displayed)]
MS (ESI) m/z 831.29 [M + 1]+
1891[Figure (not displayed)]
MS (ESI) m/z 740.33 [M + 1]+
1892[Figure (not displayed)]
MS (ESI) m/z 817.32 [M + 1]+
1893[Figure (not displayed)]
MS (ESI) m/z 722.34 [M + 1]+
1894[Figure (not displayed)]
MS (ESI) m/z 799.27 [M + 1]+
1895[Figure (not displayed)]
MS (ESI) m/z 716.5 [M + 1]+
1896[Figure (not displayed)]
MS (ESI) m/z 716.33 [M + 1]+
1897[Figure (not displayed)]
MS (ESI) m/z 702.46 [M + 1]+
1898[Figure (not displayed)]
LCMS 1.90 (ESI) m/z 669.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.97 (s, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.40 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.50- 7.41 (m, 2H), 7.36 (s, 1H), 7.23- 7.09 (m, 2H), 4.40 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 4.9 Hz, 2H), 3.55 (d, J = 4.8 Hz, 2H), 3.38-3.24 (m, 3H), 2.71-2.62 (m, 2H), 2.46 (s, 3H), 2.33 (p, J = 1.9 Hz, 1H), 1.75 (s, 3H)
1982[Figure (not displayed)]
MS (ESI) m/z 461.0 [M + 1]+
1983[Figure (not displayed)]
MS (ESI) m/z 497.0 [M + 1]+
1984[Figure (not displayed)]
MS (ESI) m/z 655.19 [M + 1]+
1985[Figure (not displayed)]
MS (ESI) m/z 734.34 [M + 1]+
2020[Figure (not displayed)]
MS (ESI) m/z 627.43 [M + 1]+
2021[Figure (not displayed)]
MS (ESI) m/z 806.23 [M + 1]+
2022[Figure (not displayed)]
MS (ESI) m/z 731.29 [M + 1]+
2029[Figure (not displayed)]
MS (ESI) m/z 746.25 [M + 1]+
2023[Figure (not displayed)]
MS (ESI) m/z 790.3 [M + 1]+
2024[Figure (not displayed)]
MS (ESI) m/z 713.31 [M + 1]+
2025[Figure (not displayed)]
MS (ESI) m/z 789.36 [M + 1]+
2032[Figure (not displayed)]
2030[Figure (not displayed)]
MS (ESI) m/z 837.28 [M + 1]+
2031[Figure (not displayed)]
MS (ESI) m/z 705.34 [M + 1]+
2041[Figure (not displayed)]
MS (ESI) m/z 807.38 [M + 1]+
2038[Figure (not displayed)]
MS (ESI) m/z 718.1 [M + 1]+
2039[Figure (not displayed)]
MS (ESI) m/z 734.37 [M + 1]+
2042[Figure (not displayed)]
MS (ESI) m/z 807.38 [M + 1]+
Example 2
The 7-CF3-thienylpyridine and derivative compounds in Table 2 can be synthesized using methods described in Example 2. Many of the reactions described in Example 1 were used to synthesize compounds in Table 2. For some compounds, some of the reactions described in Example 3, below, can be used to prepare the compounds.
[Figure (not displayed)]
To a solution of diisopropyl amine (17.8 mL, 0.123 mol) in dry tetrahydrofuran (200 mL) is added n-butyllithium (1.6 M, 66.5 mL, 0.113 mol) drop wise at −78° C. under argon atmosphere. The reaction mixture is warmed to −10° C. and stirred for 30 min. A solution of 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (1, 25.0 g, 0.102 mol) in dry tetrahydrofuran (50 mL) is added at −78° C. and mixture stirred for 45 min at −78° C. To this reaction mixture carbon dioxide gas is purged for 15 min and the temperature is gradually increased to room temperature in 2 h. After completion, the reaction mixture is cooled to −78° C. and quenched with ice water. The mixture is basified with 1 N aqueous sodium hydroxide solution and washed with diethyl ether. The aqueous layer is acidified with 2 N hydrochloric acid to pH˜1 and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated to afford 2-bromo-6-fluoro-4-(trifluoromethyl)benzoic acid (2).
[Figure (not displayed)]
To a solution 2-bromo-6-fluoro-4-(trifluoromethyl)benzamide (3, 4.5 g, crude, 15.7 mmol) in N,N-dimethylformamide (40 mL), potassium carbonate (6.5 g, 47.2 mmol) and (2,4-dimethoxyphenyl)methanamine (3.1 mL, 20.45 mmol) are added at room temperature. The reaction mixture is heated to 50° C. and stirred for 16 h. After completion of reaction, the reaction mixture is poured into ice water and extracted with ethyl acetate The organic layer is washed with brine solution, dried over anhydrous sodium sulphate, filtered, concentrated under reduced pressure to get crude. The crude is purified by column chromatography using 5% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford 2-bromo-6-((2,4-dimethoxybenzyl)amino)-4-(trifluoromethyl)benzamide (4).
To a solution of 2-bromo-6-((2,4-dimethoxybenzyl)amino)-4-(trifluoromethyl)benzamide (4, 1.0 g, 2.30 mmol) in dichloromethane (10 mL) is added trifluoroacetic acid (1.8 mL, 23.0 mmol), and the mixture is stirred for 30 min. After completion of reaction, the reaction mixture is concentrated, and the resulting crude is diluted with dichloromethane and washed with saturated sodium bicarbonate solution, brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude. The crude is purified by column chromatography using 5% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced to afford 2-amino-6-bromo-4-(trifluoromethyl)benzamide (5).
To a solution of 2-amino-6-bromo-4-(trifluoromethyl)benzamide (5, 2.0 g, 7.06 mmol) in dichloromethane (20 mL) are added triethylamine (2.93 mL, 21 mmol) and 2-fluoroacetyl chloride (1.0 mL, 14.1 mmol) at 0° C., and the reaction mixture is stirred for 30 min at same temperature. After completion of reaction, the reaction mixture is diluted with ice water and extracted with dichloromethane. The organic layer is washed with saturated brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford 2-bromo-6-(2-fluoroacetamido)-4-(trifluoromethyl)benzamide (6).
To a solution of 2-bromo-6-(2-fluoroacetamido)-4-(trifluoromethyl)benzamide (6, 0.600 g, 1.749 mmol) in ethanol (5 mL) is added 5% sodium hydroxide (4.0 mL). The mixture is heated to 110° C. and stirred for 30 min. After completion of reaction, the reaction mixture is neutralized with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with saturated brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude product. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 0-5% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford 5-bromo-2-(fluoromethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one (7).
[Figure (not displayed)]
To a solution of 7-bromo-6-fluoro-2-methyl-4-oxo-3,4-dihydroquinazoline-5-carbonitrile (5, 0.200 g, 0.7 mmol) in N,N-dimethylformamide (2 mL), copper(I) iodide (0.159 g, 0.84 mmol) and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (5a, 0.403 g, 2.1 mmol) are added and reaction mixture is heated at 100° C. for 16 h. After completion, reaction mixture is cooled; water is added to reaction mixture and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to afford 6-fluoro-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (6).
[Figure (not displayed)]
A suspension of copper(I) bromide (89.8 g, 620.1 mmol) and tert-butyl nitrite (63.8 mL, 620.1 mmol) in acetonitrile (2500 mL) is heated at 65° C. for 15 min. A solution of 2-bromo-4-fluoro-6-(trifluoromethyl)aniline (1, 100 g, 387.6 momol) in acetonitrile is added and heated the reaction mixture at 65° C. for 1 h. After completion, the reaction mass is quenched with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get the crude material. The crude compound is purified by column chromatography using 0-5% ethyl acetate in hexanes over silica gel (100-200 mesh) to afford 1,2-dibromo-5-fluoro-3-(trifluoromethyl)benzene (2).
[Figure (not displayed)]
To a stirred solution of 4-fluoro-1-methyl-2-(trifluoromethyl)benzene (1, 1.05 g, 5.89 mmol) in TFA (4 mL) is added sulfuric acid (1.25 mL) and then N-bromosuccinimide (1.05 g, 5.89 mmol). The resulting mixture is capped, covered in aluminum foil to keep light out, and stirred at room temperature overnight. The reaction mixture is poured into vigorously stirred ice water and then extracted with hexanes. The organics are washed with brine, then saturated aqueous sodium bicarbonate. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (100% hexanes) to afford 1-bromo-5-fluoro-2-methyl-3-(trifluoromethyl)benzene (2).
[Figure (not displayed)]
To a solution of 2-bromo-4-fluoro-6-(trifluoromethyl)aniline (1, 100.0 g, 389.2 mmol) in acetonitrile (2500 mL) is added p-toluenesulfonic acid (220.9 g, 1160.1 mmol) portion wise at −10° C. A solution of sodium nitrite (51.68 g, 750 mmol) and potassium iodide (157.7 g, 949.2 mmol) in water (100 mL) is added at −10° C. and the mixture is stirred for 45 min at −10° C. After completion, the reaction mixture is quenched with water & extracted with ethyl acetate (5000 mL). The organic layer is washed with aqueous saturated sodium thiosulphate (500 mL). Organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated to afford 1-bromo-5-fluoro-2-iodo-3-(trifluoromethyl)benzene (2).
To a solution of 1-bromo-5-fluoro-2-iodo-3-(trifluoromethyl) benzene (2, 80.0 g, 217.3 mmol) in N,N-dimethylformamide (500 mL), copper(I) cyanide (19.4 g, 217.2 mmol) is added at room temperature. The reaction mixture is stirred at 90° C. for 12 h. After completion, it is cooled to room temperature, poured into ice water and extracted with ethyl acetate (2.0 L). The organic layer is washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude. The crude compound is purified by flash column chromatography using 0-5% ethyl acetate in hexanes to afford 2-bromo-4-fluoro-6-(trifluoromethyl)benzonitrile (3).
To a solution 2-bromo-4-fluoro-6-(trifluoromethyl)benzonitrile (3, 12.0 g, 44.9 mmol) in tetrahydrofuran (200 mL), borane in tetrahydrofuran (1 M, 67 mL, 67.1 mmol) is added drop wise at 0° C. The reaction mixture is allowed to stir at 90° C. for 12 h. After completion, the reaction mixture is poured into chilled methanol and concentrated under reduced pressure. The crude compound is purified by flash column chromatography using 0-15% ethyl acetate in hexanes to afford (2-bromo-4-fluoro-6-(trifluoromethyl) phenyl)methanamine (4).
To a solution of (2-bromo-4-fluoro-6-(trifluoromethyl) phenyl)methanamine (4, 6.0 g, 22.6 mmol) in methanol (100 mL), paraformaldehyde (6.0 g, 200.0 mmol) and solution of sodium acetate (5.4 g, 66.0 mmol) in water (10 mL) are added and stirred at room temperature for 1 h. Sodium cyanoborohydride (4.03 g, 66.1 mmol) is added portion wise at 0° C. The reaction mixture is allowed to stir at room temperature for 12 h. After completion, the reaction mixture is concentrated under reduced pressure. Crude residue is diluted with water and extracted with diethyl ether (100 mL). The crude compound is purified by flash column chromatography using 0-15% ethyl acetate in hexanes to afford 1-(2-bromo-4-fluoro-6-(trifluoromethyl)phenyl)-N,N-dimethylmethanamine (5).
[Figure (not displayed)]
To a solution of 5-bromo-6-(hydroxymethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one (A, 0.32 g, 0.94 mmol) in dichlomethane (6 mL) at 0° C., triethyl amine (0.39 mL, 2.84 mmol) and methanesulfonyl chloride (0.11 mL, 1.42 mmol) are added and stirred at 0° C. for 1 h. After completion, the reaction mixture is diluted with water and extracted with dichloromethane. The organic layer is washed with water, saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 5-bromo-6-(chloromethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one (1)
To a solution of 4,4-difluoro piperidine (1a, 2.0 g, 12.7 mmol) in N,N-dimethylformamide (10.0 mL) is added potassium carbonate (1.06 g, 7.62 mmol) at room temperature and the mixture is stirred for 20 min. Then 5-bromo-6-(chloromethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one (1, 0.9 g, 2.54 mmol) is added to the reaction mixture at room temperature and stirring is continued for 24 h. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 50% ethyl acetate in hexane as eluent. The desired fractions are concentrated under reduced pressure to afford 5-bromo-6-((4,4-difluoropiperidin-1-yl)methyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one (2).
[Figure (not displayed)]
To a solution of 6-bromo-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (1, 50 mg, 0.151 mmol) in tetrahydrofuran (3 mL) and water (0.75 mL) are added 1-methyl-4-((trifluoro-λ4-boranyl)methyl)piperazine, potassium salt (1a, 497 mg, 2.25 mmol), cesium carbonate (196 mg, 0.602 mmol) and XPhos Chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (24 mg, 0.0301 mmol) and the mixture is sparged with argon for 5 min, then it is sealed and heated to 80° C. for 15 h. After completion, the mixture is concentrated under reduced pressure to get crude product. The crude product obtained is purified by prep-HPLC to afford 2-methyl-6-((4-methylpiperazin-1-yl)methyl)-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (2).
[Figure (not displayed)]
A solution of 6-bromo-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (1, 1.00 g, 3.02 mmol), tert-butyl 4-methylenepiperidine-1-carboxylate (1a, 5.90 g, 30.1 mmol), triethylamine (1.20 mL, 9.03 mmol), and tri (o-tolyl)phosphine (0.366 g, 1.23 mmol) in acetonitrile (10.0 mL) is degassed with argon for 10 min. Palladium (II) acetate (0.134 g, 0.60 mmol) is then added to the reaction mixture and degassing is continued for 5 min. The reaction mixture is heated at 90° C. for 24 h. After this time, the reaction mixture is cooled to room temperature, diluted with ethyl acetate, and concentrated to dryness under reduced pressure. The crude product is purified by silica gel (100-200 mesh) column chromatography using 30-50% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 4-((5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)methylene)piperidine-1-carboxylate (2).
To a solution of tert-butyl 4-((5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)methylene)piperidine-1-carboxylate (2, 0.90 g, 2.0 mmol) in methanol (20 mL) is added 10% palladium on carbon (1.35 g) at room temperature. The reaction mixture is stirred at room temperature for 2 h under hydrogen atmosphere. Then, the reaction mixture is filtered with Celite. The filtrate is washed with ethyl acetate and concentrated to dryness under reduced pressure to obtain a crude product. The crude product is purified by silica gel (100-200 mesh) column chromatography using 3-5% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 4-((5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)methyl)piperidine-1-carboxylate (3).
[Figure (not displayed)]
[Figure (not displayed)]
To a solution of 4-fluoro-2-(trifluoromethyl)aniline (1, 100.0 g, 558.66 mmol) in N,N-dimethylformamide (500 mL), N-chlorosuccinamide (78.7 g, 558.66 mmol) is added at room temperature. This reaction mixture is stirred for 16 h. After this time, the mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and then brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) column chromatography using hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-chloro-4-fluoro-6-(trifluoromethyl)aniline (2).
To a solution of 2-chloro-4-fluoro-6-(trifluoromethyl)aniline (2, 43.0 g, 201.87 mmol) in acetonitrile (200 mL) at −10° C., p-toluenesulfonic acid monohydrate (115.0 g, 605.63 mmol) is added. This reaction mixture is stirred for 15 min at the same temperature. A solution of sodium nitrite (27.85 g, 403.74 mmol) and potassium iodide (83.77 g, 504.67 mmol) in water (50 mL) is added dropwise to the reaction mixture as it is stirred at −10° C. for 30 min. Next, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with aqueous saturated sodium thiosulfate solution and then brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) column chromatography using hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 1-chloro-5-fluoro-2-iodo-3-(trifluoromethyl)benzene (3).
To a solution of 1-chloro-5-fluoro-2-iodo-3-(trifluoromethyl)benzene (3, 30 g, 92.6 mmol) in N,N-dimethylformamide (200 mL), copper(I) cyanide (12.36 g, 138.88 mmol) is added. This reaction mixture is heated at 100° C. for 16 h. After this time, the mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) column chromatography using 3% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-chloro-4-fluoro-6-(trifluoromethyl)benzonitrile (4).
To a solution of 2-chloro-4-fluoro-6-(trifluoromethyl)benzonitrile (4, 15.0 g, 67.26 mmol) in dry dichloromethane (150 mL) at −78° C., diisobutylaluminiumhydride (1.0 M in toluene, 134.52 mL, 134.52 mmol) is added dropwise. The mixture is stirred at same temperature for 30 min. Next, the reaction mixture is quenched with 1 N aqueous hydrochloric acid and extracted with dichloromethane. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to afford 2-chloro-4-fluoro-6-(trifluoromethyl)benzaldehyde (5).
To a solution of 2-chloro-4-fluoro-6-(trifluoromethyl)benzaldehyde (5, 17.00 g, 75.22 mmol) in tetrahydrofuran (100 mL), 2-methylpropane-2-sulfinamide (5a, 13.65 g, 112.83 mmol) and titanium ethoxide (34.30 mL, 150.44 mmol) are added dropwise at room temperature. This reaction mixture is stirred at the same temperature for 16 h. After this time, the reaction mixture is quenched with aqueous ammonium chloride solution, filtered with Celite, and washed with ethyl acetate. The filterate is concentrated and the crude residue is purified by Combi-flash (40 g, Redi-Sep column) using 20% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford (E)-N-(2-chloro-4-fluoro-6-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (6).
Magnesium turnings (5.0 g) are added to dry tetrahydrofuran (50 mL) followed by iodine (0.002 g) and the mixture is heated to just above room temperature. Then, 2-(2-bromoethyl)-1,3-dioxane (6a, 9.8 mL, 72.94 mmol) is added and the mixture is heated till it became colorless. Then, this mixture is added dropwise to a solution of (E)-N-(2-chloro-4-fluoro-6-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (6, 12.00 g, 36.47 mmol) in tetrahydrofuran (50 mL) at room temperature. The resulting mixture is stirred at room temperature for 1 h. Next, the reaction mixture is quenched with aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer dried over anhydrous sodium sulfate and concentrated. The crude residue is purified by Combi-flash (40 g, Redi-Sep column) using 30% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford N-(1-(2-chloro-4-fluoro-6-(trifluoromethyl)phenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (7).
A solution mixture of N-(1-(2-chloro-4-fluoro-6-(trifluoromethyl)phenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (7, 12.00 g, 26.96 mmol) in trifluroacetic acid in water (3:1, 180 mL) is stirred at room temperature for 16 h. After this time, the reaction mixture is quenched with aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The solid residue is dissolved in methanol, after which sodium borohydrate (8.00 g, 269.66 mmol) is added at 0° C. and the mixture is stirred at room temperature for 8 h. After this time, the reaction mixture is quenched with ice-cold water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to afford 2-(2-chloro-4-fluoro-6-(trifluoromethyl)phenyl)pyrrolidine (8).
[Figure (not displayed)]
To a solution of 2,3-difluoro-4-(trifluoromethyl)benzoic acid (1, 5 g, 22.123 mmol) in N,N-dimethylformamide (50 mL), N-iodosuccinimide (7.43 g, 33.185 mmol) is added and purged with argon for 20 min. Then, palladium acetate (1.48 g, 6.637 mmol) is added and reaction mixture is heated at 100° C. for 48 h. After completion, the reaction mixture is cooled, diluted with water and extracted with ethyl acetate. The combined organic layer is washed with cold water and brine solution, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford 2,3-difluoro-6-iodo-4-(trifluoromethyl)benzoic acid (2).
[Figure (not displayed)]
To a solution 2-bromo-4-chlorophenol (7, 50.0 g, 241.0 mmol) in aqueous sodium hydroxide (1 M) (1.0 L), tetra-n-butylammonium bromide (11.64 g, 36.15 mmol) and potassium iodide (6.00 g, 36.15 mmol) are added. 1,2-dibromoethane (8,165.6 g, 891.7 mmol) is added at 85° C. and stirred for 16 h at the same temperature. After completion, the reaction mixture is poured into water and extracted with ethyl acetate. Combined organic layer are washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude; the crude compound is purified by flash column chromatography (using 0-5% ethyl acetate in hexanes) to afford 2-bromo-1-(2-bromoethoxy)-4-chlorobenzene (9).
[Figure (not displayed)]
A stirred solution of thieno[3,2-b]pyridin-7-ol (1, 2.0 g, 13.2 mmol) in phosphorous oxybromide (7.5 g, 26.4 mmol) and 1,2-dichloroethane is heated at 90° C. for 12 h. After completion of the reaction, the mixture is cooled to room temperature and quenched with saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer is washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated to afford 7-bromothieno[3,2-b]pyridine (2).
To a stirred solution of 7-bromothieno[3,2-b]pyridine (2, 1.5 g, 7.04 mmol) in dry tetrahydrofuran (20 mL), freshly prepared lithium diisopropylamide (2.0 M in hexane, 8.75 mL, 17.5 mmol) is added at −78° C. and the mixture is stirred at same temperature for 1 h. Hexachloroethane (2.0 mL, 8.44 mmol) is added drop wise and the reaction mixture is allowed to warm up to room temperature over 3 h. The reaction is quenched with aqueous ammonium chloride solution, diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is purified over a plug of silica gel eluting the compound with ethyl acetate in hexanes (0-10%). The desired fractions are concentrated under reduced pressure to afford 7-bromo-2-chlorothieno[3,2-b]pyridine (3).
To a solution of 7-bromo-2-chlorothieno[3,2-b]pyridine (3, 0.5 g, 2.02 mmol) in dry tetrahydrofuran (10 mL) and the mixture is cooled to −78° C. Lithium diisopropylamide (2 M, 1.5 mL, 3.03 mmol) is added drop wise and the reaction mixture is stirred at −78° C. for 1 h. Carbon dioxide gas is purged through the reaction mass for 20 min at same temperature and is stirred for 1 h at −78° C. The reaction mixture is slowly warmed to 0° C. and stirred for 30 min. After completion, reaction mixture is quenched with water and washed with ethyl acetate. Ethyl acetate layer is discarded and aqueous layer is acidified with aqueous solution of citric acid. It is then extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford 7-bromo-2-chlorothieno[3,2-b]pyridine-3-carboxylic acid (4).
[Figure (not displayed)]
To a stirred solution of 7-chlorothieno[3,2-b]pyridine (1, 1.5 g, 8.9 mmol) in dry tetrahydrofuran (50 mL) is added drop wise lithium diisopropylamide (11.7 mL, 19.5 mmol) at −78° C. and the mixture is stirred at same temperature for 1 h. Iodine (2.25 g, 8.87 mmol dissolved in tetrahydrofuran, 10 mL) is added drop wise and the reaction mixture is allowed to warm up to room temperature over 4 h. It is quenched with aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer is washed with water and saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 5-10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 7-chloro-2-iodothieno[3,2-b]pyridine (2).
To a solution of 7-chloro-2-iodothieno[3,2-b]pyridine (2, 1.0 g, 3.4 mmol) in N,N-dimethylformamide (10 mL), N-bromo succinamide is added at room temperature. The reaction mixture is heated and stirred at 70° C. for 12 h. After completion of the reaction, the mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 5-10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 3-bromo-7-chloro-2-iodothieno[3,2-b]pyridine (3).
A suspension 3-bromo-7-chloro-2-iodothieno[3,2-b]pyridine (3, 1.0 g, 2.7 mmol) and tributyl vinyl tin (1.01 mL, 3.21 mmol) in 1,4-dioxane (10 mL) is degassed using argon for 10 min. Tetrakis(triphenylphosphine)palladium(0) (0.21 g, 0.19 mmol) is added to the reaction mixture at room temperature and the mixture is heated at 100° C. for 1 h. After completion, the reaction mixture is cooled to room temperature, diluted with water and extracted with ethyl acetate. The ethyl acetate layer is dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude product is purified over a plug of silica gel eluting the compound with ethyl acetate:hexanes (1-10%). The desired fractions are concentrated under reduced pressure to afford 3-bromo-7-chloro-2-vinylthieno[3,2-b]pyridine (4).
To a solution of 3-bromo-7-chloro-2-vinylthieno[3,2-b]pyridine (4, 0.6 g, 2.19 mmol) in dry tetrahydrofuran (20 mL) is added drop wise n-Butyl lithium (1.7 mL 1.3 M in hexanes, 2.19 mmol) at −78° C. and reaction mixture is stirred at the same temperature for 2 h. Carbon dioxide gas is purged through the reaction mixture at −78° C. for 30 min and the reaction mixture is stirred for 1 h at the same temperature. The reaction mixture is slowly warmed to 0° C. and stirred for 30 min. After completion, reaction mixture is quenched with water and washed with ethyl acetate. Ethyl acetate layer is discarded and aqueous layer is acidified with aqueous solution of citric acid and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford 7-chloro-2-vinylthieno[3,2-b]pyridine-3-carboxylic acid (5).
[Figure (not displayed)]
Methyl 7-bromothieno[3,2-b]pyridine-3-carboxylate (1, 68.0 mg, 0.25 mmol) and bis(trifluoromethylsulfinyloxy)zinc (1a, 139.8 mg, 0.50 mmol) are dissolved in dimethylsulfoxide (1.71 mL) in an oven-dried screw capped vial equipped with a stir bar. The mixture is stirred vigorously at 0° C. while tert-butyl hydroperoxide (0.09 mL, 0.92 mmol) is added slowly. After completion of addition the ice bath is removed and the reaction mixture is heated to 50° C. in a heating block for 2.5 h before being cooled to room temperature. The reaction mixture is diluted with saturated aqueous sodium bicarbonate and ethyl acetate. The layers are separated and the aqueous phase extracted with ethyl acetate three times. The combined organic material is washed with brine and dried over magnesium sulfate. The solids are filtered and solvent removed in vacuo to afford a crude residue that is purified via silica gel chromatography (5 to 40% ethyl acetate in hexanes), affording methyl 7-bromo-2-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxylate (2).
[Figure (not displayed)]
A solution of tert-butyl 7-bromothieno[3,2-b]pyridine-3-carboxylate (1, 150.0 mg, 0.480 mmol), (3-oxo-1λ{3},2-benziodoxol-1-yl) acetate (417.5 mg, 0.950 mmol), 2-(tert-butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1a, 132.0 mg, 0.720 mmol) and tris(2,2′-bipyridyl)dichloro-ruthenium(II)hexahydrate (35.7 mg, 0.048 mmol) in hexafluoroisopropanol (1.25 mL) is stirred at room temperature and irradiated with a 60 watt household lamp positioned 10 cm away from the vial for 24 h. After completion, reaction mixture is diluted with dichloromethane and silica gel is added. The solvent is evaporated. The crude silica mixture is purified by flash chromatography using silica gel (100-200 mesh) using 0-10% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-bromo-2-(tert-butyl)thieno[3,2-b]pyridine-3-carboxylate (2).
[Figure (not displayed)]
Methyl 7-chlorothieno[3,2-b]pyridine-3-carboxylate (1, 0.2 g, 0.88 mmol) is dissolved in dichloromethane (2.2 mL) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at room temperature while 3-chloroperbenzoic acid (0.24 g, 1.41 mmol) is added in 4 portions over 2 min. After 24 h the reaction mixture is poured onto silica gel and purification via silica gel chromatography (50-100% ethyl acetate in hexanes, then 10% methanol in ethyl acetate) afforded 7-chloro-3-(methoxycarbonyl)thieno[3,2-b]pyridine 4-oxide (2).
7-chloro-3-(methoxycarbonyl)thieno[3,2-b]pyridine 4-oxide (2, 0.12 g, 0.47 mmol) is dissolved in dichloromethane (3.3 mL) in an oven-dried screw capped vial equipped with a stir bar. The mixture is stirred at room temperature while methanesulfonyl chloride (0.18 mL, 2.36 mmol) dropwise. After 3 h more methanesulfonyl chloride (0.18 mL, 2.36 mmol) is added dropwise. After 4.5 h the reaction mixture is warmed to 40° C. and stirred an additional 16 h before being cooled to room temperature. The reaction mixture is poured onto silica gel and purification via silica gel chromatography (0-50% ethyl acetate in hexanes) afforded methyl 5,7-dichlorothieno[3,2-b]pyridine-3-carboxylate (3).
Zinc chloride solution (0.5 M, 0.59 mL, 0.29 mmol) is dissolved in tetrahydrofuran (1.0 mL) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at room temperature while bromo(cyclopropyl)magnesium (0.59 mL, 0.29 mmol) solution is added slowly. After 45 min a solution of methyl 5,7-dichlorothieno[3,2-b]pyridine-3-carboxylate (3, 67.0 mg, 0.25 mmol) in tetrahydrofuran (1.5 mL) is added slowly. After 1 min Pd2(dba)3 (28.4 mg, 0.03 mmol) and dppf (30.4 mg, 0.06 mmol) are added and the reaction mixture subsequently heated to 60° C. for 1 h. The reaction mixture is cooled to room temperature and poured onto saturated aqueous NH4Cl. The aq. phase is extracted with ethyl acetate three times. The combined organic material is washed with brine and dried over magnesium sulfate, filtered and solvent removed in vacuo to provide a brown oil. Purification via silica gel chromatography (8-29% ethyl acetate in hexanes) afforded methyl 7-chloro-5-cyclopropylthieno[3,2-b]pyridine-3-carboxylate (4).
[Figure (not displayed)]
7-bromo-3-(methoxycarbonyl)thieno[3,2-b]pyridine 4-oxide (2, 148 mg, 0.514 mmol) is dissolved in chloroform (10 mL) and POCl3 (0.48 mL, 0.79 g, 5.1 mmol) is added. The vial is sealed and the mixture is stirred at 60° C. for 4 h, then over night at room temperature. Then the mixture is concentrated, taken up in DCM, washed with NaHCO3(aq), dried (Na2SO4), filtered, and concentrated. The crude product (140 mg) is dissolved in THF (9 mL) and sodium methanolate (25% in MeOH, 0.12 mL, 0.12 g, 0.52 mmol) is added. The mixture is stirred at room temperature for 2.75 h, and another 0.13 mL NaOMe sln (25% in MeOH) are added. After 30 min another 0.04 mL NaOMe sln (25% in MeOH) are added. After another 10 min another 0.04 mL NaOMe sln (25% in MeOH) are added. Then the mixture is diluted with DCM and washed with water. The organic phase is dried (Na2SO4), filtered, concentrated. Purification by column chromatography yielded 23.9 mg of a 3:1 mixture of 3′ and 3.
[Figure (not displayed)]
To a solution of tert-butyl 7-bromo-5-(bromomethyl)thieno[3,2-b]pyridine-3-carboxylate (2, 200.0 mg, 0.491 mmol) in N,N-dimethylpyrrolidone (3 mL) is added tert-butyl N-tert-butoxycarbonylcarbamate (160.1 mg, 0.736 mmol) and potassium carbonate (203.6 mg, 1.473 mmol) and the reaction mixture is stirred at room temperature for 24 h. After completion, reaction mixture is diluted with dichloromethane and silica gel is added. The solvent is evaporated. The crude silica mixture is purified by Isco column chromatography using 0-10% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 5-[[bis(tert-butoxycarbonyl)amino]methyl]-7-bromo-thieno[3,2-b]pyridine-3-carboxylate (3).
[Figure (not displayed)]
A suspension of methyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 3.50 g, 12.3 mmol) in formalin (37-40%) 10 mL is irradiated in microwave at 120° C. for 1 h. After 1 h, the reaction mass is cooled and extracted with ethyl acetate. The starting material is not consumed in 1 h, reaction is irradiated again after work-up 3 times under microwave. The reaction is monitored by LCMS, still 50% starting material is remaining. The reaction mass is cooled and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue is purified by column chromatography using silica (100-200 mesh) and 0-40% ethyl acetate in hexane to afford methyl 7-bromo-5-(2-hydroxyethyl)thieno[3,2-b]pyridine-3-carboxylate (2).
To a solution of methyl 7-bromo-5-(2-hydroxyethyl)thieno[3,2-b]pyridine-3-carboxylate (2, 0.32 g, 1.01 mmol) in pyridine (10 mL), acetic anhydride (0.115 mL, 1.22 mmol) is added to the reaction mixture. The reaction mixture is stirred at room temperature for 16 h. After completion of reaction as confirmed on thin layer chromatography and LCMS, reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The crude is purified by combi flash (4 g, Redi Sep column) using 50% ethyl acetate in hexanes as eluent to afford methyl 5-(2-acetoxyethyl)-7-bromothieno[3,2-b]pyridine-3-carboxylate (3).
[Figure (not displayed)]
To a solution of 4-chloro-3-fluorophenol (1, 3.0 g, 20.59 mmol) in acetone (30 mL) iodomethane (5.2 mL, 82.00 mmol) and potassium carbonate (5.6 g, 41.00 mmol) are added at room temperature and reaction mixture is stirred at 60° C. for 12 h. After completion of reaction as confirmed on thin layer chromatography, reaction mass is evaporated and reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get afford 1-chloro-2-fluoro-4-methoxybenzene (2).
To a solution of 1-chloro-2-fluoro-4-methoxybenzene (2, 1.9 g, 11.84 mmol) in tetrahydrofuran (20 mL), lithium di-isopropylamide (2 M in tetrahydrofuran) (11.8 mL, 23.75 mmol) is added drop wise at −78° C. and reaction mixture is stirred at same temperature for 1 h. Then Tri-Iso propyl Borate (3.26 mL, 14.16 mmol) is added dropwise at −78° C. The reaction mixture is stirred for 2 h at room temperature. After completion reaction, reaction mixture is quenched with saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. The crude compound obtained is purified by combi flash chromatography using 12 gm redisep column eluting with 80% ethyl acetate in hexane to afford of (3-chloro-2-fluoro-6-methoxyphenyl)boronic acid (3).
To a solution of (3-chloro-2-fluoro-6-methoxyphenyl)boronic acid (3, 0.35 g, 1.71 mmol) in dichloromethane (5 mL) Boron tribromide (0.324 mL, 3.43 mmol) is added drop wise at 0° C. and reaction mixture is stirred at room temperature for 1 h. After completion of reaction as confirmed on thin layer chromatography the reaction mixture is quenched with ice cold water. The solid precipitated is filtered and washed with pentane to afford as (3-chloro-2-fluoro-6-hydroxyphenyl)boronic acid (4).
A suspension of tert-butyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (4a, 0.230 g 0.8 mmol), (3-chloro-2-fluoro-6-hydroxyphenyl)boronic acid (4, 0.30 g, 1.6 mmol) and potassium carbonate (0.334 g, 2.4 mmol) in 1,4-dioxane (2.0 mL) and water (0.5 mL) is degassed with argon gas 10 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (0.03 g, 0.04 mmol) is added to above suspension and reaction mixture is stirred for 3 h at 90° C. The reaction mixture is monitored with LCMS and thin layer chromatography reaction mixture. After completion, the reaction mass is filtered through Celite bed and washed with ethyl acetate. The crude compound obtained is purified through combi flash chromatography using 4 gm redisep column by eluting with 90% ethyl acetate in hexane to afford tert-butyl 7-(3-chloro-2-fluoro-6-hydroxyphenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (5).
[Figure (not displayed)]
To a solution of 2,5-dimethylpyridine (1, 10.0 g, 93.4 mmol) in Chloroform (100 mL) is added to metachloroperbenzoic acid (19.3 g, 112.1 mmol) at 0° C. under argon atmosphere and mixture is stirred at room temperature for 16 h. After completion, the reaction mixture is diluted with 10% calcium hydroxide solution and the solution is filtered through celite, filtrate is concentrated and dried to afford 2,5-dimethylpyridine 1-oxide (2).
To a solution of 2,5-dimethylpyridine 1-oxide (2, 10.0 g, 81.3 mmol) in dichloromethane (100 ml) is added to Trimethylsilylcyanide (11.2 g, 89.4 mmol) at 0° C. under argon atmosphere and stirred at room temperature for 30 minute, diethylcarbamic chloride (2a, 11.3 mL, 89.4 mmol) is added and stirring continued at room temperature for 24 h. After completion, the reaction mixture is quenched with 10% potassium carbonate solution and extracted with ethyl acetate. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The crude product is purified by column chromatography using silica (100-200 mesh) using 30-40% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 3,6-dimethylpicolinonitrile (3).
To a solution of 3,6-dimethylpicolinonitrile (3, 7.00 g, 46.9 mmol) in Chloroform (70 mL) is added to metachloroperbenzoic acid (8.75 g, 56.6 mmol) at 0° C. under argon atmosphere and stirring continued at room temperature for 16 h. After completion, the reaction mixture is diluted with 10% calcium hydroxide solution and filtered through celite, filtrate is concentrated and dried to afford 2-cyano-3,6-dimethylpyridine 1-oxide (4).
A solution of 2-cyano-3,6-dimethylpyridine 1-oxide (4, 7.0 g, 46.9 mmol) in phosphoryl chloride (50 mL) is stirred at 90° C. for 4 h. After completion, the reaction mixture is concentrated and purified by column chromatography using silica (100-200 mesh) using 20-30% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 4-chloro-3,6-dimethylpicolinonitrile (5).
A solution of 4-chloro-3,6-dimethylpicolinonitrile (5, 4.0 g, 24.0 mmol) in ethanol (20 mL) and 10% Potassium hydroxide solution (20 mL) is stirred at 100° C. for 16 h. After completion, the reaction mixture is cooled and acidified with 2M hydrochloric acid solution up to pH 5 and extracted with ethyl acetate. Organic layer is dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. To afford 4-chloro-3,6-dimethylpicolinic acid (6).
To a solution of 4-chloro-3,6-dimethylpicolinic acid (6, 1.50 g, 8.10 mmol) in tert-butyl alcohol (9.0 ml) is added di-tert-butyl dicarbanate (0.75 mL, 3.56 mmol) and 4-dimethylamino pyridine (1.48 g, 12.1 mmol) at 0° C. under argon atmosphere and stirred at 90° C. for 4 h. After completion, the reaction mixture is concentrated under reduced pressure. The crude compound is purified by flash column chromatography using 20-30% ethyl acetate in hexane to afford tert-butyl 4-chloro-3,6-dimethylpicolinate (7).
[Figure (not displayed)]
To a stirred solution of thieno [3,2-b]pyridin-7-ol (1, 5.0 g, 33.07 mmol) in 1,2-dichloroethane (50 mL) is added phosphorous oxybromide (143.21 g, 496.09 mmol) portionwise at room temperature and the mixture is stirred at 70° C. for 10 h. The reaction mixture is cooled at 0° C., basified with 10% aqueous solution of sodium hydroxide and extracted with dichloromethane. The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to afford 7-bromothieno[3,2-b]pyridine (2).
To a stirred solution of 7-bromothieno[3,2-b]pyridine (2, 4.0 g, 18.78 mmol) in dry tetrahydrofuran (40 mL) is added lithium diisopropylamide solution (2.0 M in hexanes, 26.30 mL, 53.60 mmol) drop wise at −78° C. and the mixture is stirred at same temperature for 1 h. Carbon dioxide gas is purged through the reaction mass for 15 min and the reaction mixture is allowed to warm up to room temperature over 4 h. The reaction is quenched with aqueous ammonium chloride solution, diluted with water and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulphate, filtered and concentrated to afford 7-bromothieno[3,2-b]pyridine-2-carboxylic acid (3).
[Figure (not displayed)]
To a stirred solution of (4-methoxyphenyl)methanethiol (12.3 g, 87.77 mmol) in N,N-dimethylformamide (150 mL) is added sodium hydride (4.60 g, 119.69 mmol) portion wise at 0° C. After 10 min, 1-bromo-2-fluoro-4-methylbenzene (1, 15.0 g, 79.79 mmol) is added and the reaction is stirred at room temperature for 2 h. After completion, the reaction is poured into ice water and extracted with ethyl acetate. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get the crude. The crude product is purified by Combiflash (40 g, RediSep column) using 0-5% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford (2-bromo-5-methylphenyl)(4-methoxybenzyl)sulfane (2).
To a solution of (2-bromo-5-methylphenyl)(4-methoxybenzyl)sulfane (2, 18.0 g, 55.90 mmol) in dichloromethane (140 mL) is added a mixture of trifluoroacetic acid (20 mL) and triflic acid (5 mL) in dichloromethane (40 mL) at 0° C. drop wise and the reaction mixture is stirred at room temperature for 2 h. After completion, the reaction is poured into ice-water and extracted with dichloromethane. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get the crude product 2-bromo-5-methylbenzenethiol (3).
To a solution 2-bromo-5-methylbenzenethiol (3, 4.7 g, 23.27 mmol) in acetone (47.0 mL) is added potassium carbonate (16.0 g, 116.35 mmol) at room temperature and the mixture is stirred for 10 min. 3-Bromo-2-oxopropanoic acid (3a, 11.6 g, 69.80 mmol) is added to the reaction mixture and stirred for 5 h at room temperature. After completion, the acetone is evaporated under reduced pressure; the residue is diluted with water and extracted with ethyl acetate. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get 3-((2-bromo-5-methylphenyl)thio)-2-oxopropanoic acid (4).
To a solution of 3-((2-bromo-5-methylphenyl)thio)-2-oxopropanoic acid (4, 4.0 g, 13.89 mmol) in dichloromethane (40.0 mL) is added sulfuric acid (10.0 mL) and the reaction mixture is stirred at room temperature for 5 h. After completion, the reaction mixture is poured into ice water, extracted with dichloromethane. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get 7-bromo-4-methylbenzo[b]thiophene-3-carboxylic acid (5).
To a solution 7-bromo-4-methylbenzo[b]thiophene-3-carboxylic acid (5, 3.0 g, 11.11 mmol) in N,N-dimethylformamide (30.0 mL) is added potassium carbonate (4.6 g, 33.33 mmol) and iodomethane (1.4 mL, 22.22 mmol) at 0° C. and the reaction mixture is stirred at room temperature for 4 h. After completion, the reaction mass is poured into water and extracted with ethyl acetate. The organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure; the crude product is purified by flash column chromatography using 5% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford methyl 7-bromo-4-methylbenzo[b]thiophene-3-carboxylate (6).
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To a solution of tert-butyl 4-bromo-7-chlorobenzo[b]thiophene-3-carboxylate (1, 0.7 g, 2.01 mmol) in N,N-dimethylformamide (2 mL), copper(I) cyanide (0.180 g, 2.01 mmol) is added. This reaction mixture is heated at 90° C. for 2 h. After this time, the reaction mixture is filtered with Celite and washed with ethyl acetate. The filtrate is washed with water and then brine solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. This is purified by column chromatography using silica gel (100-200 mesh) and 30-50% ethyl acetate in hexane as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-chloro-4-cyanobenzo[b]thiophene-3-carboxylate (2).
[Figure (not displayed)]
A solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (1, 0.41 g, 2.84 mmol) and diethoxymethoxyethane (50.0 mL) is stirred and heated at 90° C. for 2 h in a closed vessel. Methyl 3-aminothiophene-2-carboxylate hydrochloride (1a, 0.5 g, 2.58 mmol) is added portion wise at 90° C. under argon atmosphere and continued heating at 90° C. for 12 h. After completion, the reaction mass is cooled to room temperature, added water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated under vacuo to get crude. The crude is triturated with diethyl ether to afford methyl 3-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)thiophene-2-carboxylate (2).
A solution of methyl 3-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)thiophene-2-carboxylate (2, 0.200 g, 0.61 mmol) in N-methyl pyrrolidone (15 mL) is heated in microwave at 200° C. for 30 min. After completion, the reaction mass is cooled to room temperature, filtered and the crude solid is purified by prep-HPLC to afford methyl 4-hydroxy-2-methylthieno[3,4-b]pyridine-7-carboxylate (3).
[Figure (not displayed)]
To a stirred solution of 7-chloro-3-methylthieno[3,2-b]pyridine (1, 1.0 g, 5.44 mmol) in ethyleacetate (10 mL) are added 1-bromopyrrolidine-2,5-dione (1a, 1.93 g, 10.8 mmol) and azobisisobutyronitrile (0.088 g, 0.540 mmol) at room temperature. The reaction is stirred at 60° C. for 4 h. After completion, the reaction mixture is quenched with water and extracted with ethyl acetate. The organic layer is washed with brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 1-5% ethylacetate in hexanes as eluent to afford 3-(bromomethyl)-7-chlorothieno[3,2-b]pyridine (2).
To a solution of 3-(bromomethyl)-7-chlorothieno[3,2-b]pyridine (2, 1.50 g, 5.70 mmol) in N,N-dimethylformamide (15 mL) is added sodium cyanide (0.561 g, 11.40 mmol) and the mixture is stirred at room temperature for 3 h. After completion, the reaction is quenched with ice cold water and extracted with ethyl acetate. The organic layer is washed with cold water, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to afford 2-(7-chlorothieno[3,2-b]pyridin-3-yl)acetonitrile (3).
To a solution of 2-(7-chlorothieno[3,2-b]pyridin-3-yl)acetonitrile (3, 1.10 g, 5.20 mmol) in a mixture of ethanol and water (1:1, (20 mL) is added potassium hydroxide (2.96 g, 52.8 mmol) and the mixture is stirred at 60° C. for 10 h. After completion, the reaction mixture is concentrated and extracted with diethyl ether. The aqueous layer is acidified with 1 N aqueous hydrochloric acid solution, and extracted with ethyl acetate. The organic layer is washed with saturated brine solution, dried over anhydrous sodium sulphate, filtered and concentrated to afford 2-(7-chlorothieno[3,2-b]pyridin-3-yl)acetic acid (4).
[Figure (not displayed)]
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To a solution of 1H-pyrrolo[3,2-b]pyridine (1, 2.5 g, 21 mmol) in DCM (75 mL) at 0° C. is slowly added m-CPBA (5.69 g, 25.4 mmol). The mixture is stirred from 0° C. to rt. After 16 h the reaction is complete as judged by TLC (SiO2, 10% MeOH/DCM). The mixture is concentrated and the residue purified by column chromatography (SiO2, 0-20% MeOH/DCM). The product is isolated as a mixture with m-CBA (ratio ca. 1:0.7 by 1H-NMR). The so-obtained material 1H-pyrrolo[3,2-b]pyridine 4-oxide (2).
1H-pyrrolo[3,2-b]pyridine 4-oxide (2, 3.64 g) in POCl3 (30 mL, 50 g, 0.32 mol) are refluxed overnight under argon (oil-bath, 130° C.). Then the mixture is carefully transferred into an Erlenmeyer flask with crushed ice with stirring. The mixture is then basified with NaOH (aq, 12.5%) to pH ca. 8, and the precipitated material is collected by filtration. The aq. phase is extracted (3×EtOAc), and the combined organic phases are dried (Na2SO4), filtered and concentrated. The precipitated and extracted material are combined, dissolved in DCM and washed with NaHCO3(aq). The organic phase is dried (Na2SO4), filtered and concentrated to afford 7-chloro-1H-pyrrolo[3,2-b]pyridine (3).
The reaction is run in two batches (0.80 g of (3) per batch), and the two batches are combined for purification purposes. To a solution of 7-chloro-1H-pyrrolo[3,2-b]pyridine (3, 0.80 g, 5.2 mmol) in 1,4-dioxane (14 mL) and water (3.5 mL) are added (5-chloro-2-hydroxyphenyl)boronic acid (3a, 1.4 g, 8.1 mmol) and potassium carbonate (2.2 g, 16 mmol) and the mixture is degassed by bubbling argon through it for 5 min. Pd(PPh3)4 (0.61 g, 0.53 mmol) is added, and the mixture is degassed for another 5 min, then placed in a preheated heating block (100° C.) and stirred for 20 h. Then the mixture is cooled down to room temperature. The two batches are combined, diluted with water, extracted with EtOAc. The organic phase is dried (Na2SO4), filtered, and concentrated. Purification by column chromatography (SiO2, 0-20% MeOH/DCM) to afford 4-chloro-2-(1H-pyrrolo[3,2-b]pyridin-7-yl)phenol (4).
To a solution of 4-chloro-2-(1H-pyrrolo[3,2-b]pyridin-7-yl)phenol (4, 37 mg, 0.15 mmol) in DMF (0.7 mL) at 0° C. are added imidazole (23 mg, 0.34 mmol) and tert-butyl-chloro-diphenyl-silane (0.05 mL, 0.05 g, 0.2 mmol), and the mixture is stirred at rt. After 3 h the mixture is diluted with water and EtOAc, and the aq. phase is extracted (3×EtOAc). The combined organic phases are dried (Na2SO4), filtered and concentrated. Purification by column chromatography (SiO2, 0-40% EtOAc/hexane) to afford 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-1H-pyrrolo[3,2-b]pyridine (5).
To a solution of 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-1H-pyrrolo[3,2-b]pyridine (5; 1.08 g, 2.24 mmol) in THF (20 mL) at 0° C. is added N-Iodosuccinimide (503 mg, 2.24 mmol) and the mixture is stirred for 10 min. Then the reaction is diluted with EtOAc, quenched with Na2S2O3(aq) and water, and extracted (2×EtOAc). The combined organic phases are dried, filtered and concentrated. Purification by column chromatography (SiO2, 0-40% EtOAc/hexane) afforded to afford 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-3-iodo-1H-pyrrolo[3,2-b]pyridine (6).
To a solution of 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-3-iodo-1H-pyrrolo[3,2-b]pyridine (6, 990 mg, 1.63 mmol) in MeCN (11 mL) at 0° C. are added triethylamine (0.45 mL, 0.33 g, 3.2 mmol), di-tert-butyl dicarbonate (531 mg, 2.43 mmol) in 2 mL MeCN and 4-dimethylaminopyridine (40 mg, 0.33 mmol) and the mixture is stirred at rt. After 1 h water is added, and the mixture is extracted with DCM (3×). The combined organic phases are dried (Na2SO4), filtered and concentrated. Purification by column chromatography (SiO2, 0-20% EtOAc/hexane) to afford tert-butyl 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-3-iodo-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (7).
To a solution of tert-butyl 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-3-iodo-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (7, 1.06 g, 1.49 mmol) in methanol (11 mL) and DMF (4 mL) are added triethylamine (0.43 mL, 0.31 g, 3.1 mmol) and (Ph3P)2PdCl2 (105 mg, 0.149 mmol). Then the mixture is stirred at 50° C. under a CO atmosphere. After 18 h the mixture is concentrated and purified by column chromatography (SiO2, 0-50% EtOAc/hexane) to afford 1-(tert-butyl) 3-methyl 7-(2-((tert-butyldiphenylsilyl)oxy)-5-chlorophenyl)-1H-pyrrolo[3,2-b]pyridine-1,3-dicarboxylate (8).
[Figure (not displayed)]
To a solution of 3-bromo-7-chlorothieno[3,2-b]pyridine (4, 0.30 g, 1.21 mmol), and ethyl 2-bromo-2,2-difluoroacetate (4a, 0.73 g, 3.62 mmol) in dimethylsulfoxide (12.0 mL), cupper powder (0.11 g, 1.81 mmol) is added at room temperature and the mixture is heated at 60° C. for 16 h. After completion, reaction mass is diluted with ethyl acetate and filtered through Celite. The filterate is washed with water and brine solution, dried over sodium sulfate filtered and concentrated. The crude is purified by flash column chromatography using silica gel (100-200 mesh) and 20-30% ethyl acetate in hexane as eluent. The desired fractions are concentrated under reduced pressure to afford ethyl 2-(7-chlorothieno[3,2-b]pyridin-3-yl)-2,2-difluoroacetate (5).
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To a solution of N,N,N′,N′-tetramethylethylenediamine (11.69 g, 100.42 mmol) in tetrahydrofuran (100 mL), n-butyllithium (1.3 M in hexane, 71.1 mL, 92.43 mmol) is added at −78° C., then 6,7-dihydro-5H-cyclopenta[b]pyridine (1, 10.0 g, 84.03 mmol) is added dropwise and the mixture is stirred at −78° C. for 45 min. Then, a solution of dimethyl carbonate (1a, 8.31 g, 92.43 mmol) in tetrahydrofuran (10 mL) is added drop wise and the mixture is allowed to room temperature over an 1 h. The reaction mixture is quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layer is dried over anhydrous sodium sulphate, filtered and concentrated. The crude is purified by column chromatography using silica gel (100-200 mesh) and 0-25% ethyl acetate in hexane as eluent to afford methyl 6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate (2).
To a solution of methyl 6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate (2, 2.5 g, 14.12 mmol) in dichloromethane (30 mL), 3-chloroperbenzoic acid (4.85 g, 28.24 mL) is added at 0° C. and the mixture is stirred at the same temperature for 30 min. After completion, the reaction mixture is quenched with saturated sodium bicarbonate solution (10 mL) and extracted with dichloromethane. The combined organic layer is washed brine, dried over anhydrous sodium sulphate, filtered and concentrated. The crude is purified by column chromatography using silica gel (100-200 mesh) and 0-10% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford 7-(methoxycarbonyl)-6,7-dihydro-5H-cyclopenta[b]pyridine 1-oxide (3).
To a solution of 7-(methoxycarbonyl)-6,7-dihydro-5H-cyclopenta[b]pyridine 1-oxide (3, 1.5 g, 7.77 mmol) in acetonitrile (25 mL), lithium bromide (0.67 g, 7.77 mmol) and phosphorus bromide (22.3 g, 77.72 mmol) are added and the reaction mixture is heated at 80° C. for 24 h. After completion, the reaction mixture is cooled to 0° C., quenched with saturated sodium bicarbonate solution (50 mL) and extracted with ethyl acetate. The combined organic layer is dried over anhydrous sodium sulphate, filtered and concentrated. The crude is purified by column chromatography using silica gel (100-200 mesh) and 0-25% ethyl acetate in hexane to afford methyl 4-bromo-6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate (4).
[Figure (not displayed)]
To a solution of 7-bromothieno[3,2-b]pyridine-3-carbaldehyde (1, 36 mg, 0.148 mmol) in DCM (1 mL) in an oven-dried screw capped vial is equipped with a stir bar. To the mixture is added ethoxyethane trifluoroborane (0.02 mL, 0.163 mmol) with constant stirring at room tem added slowly. Then 1,2-bis((trimethylsilyl)oxy)cyclobut-1-ene (1a, 0.06 mL, 0.222 mmol) is added dropwise and the clear yellow mixture continued to stir at room temperature for 40 min. Water (0.030 mL) is added followed by ethoxyethane; trifluoroborane (0.27 mL, 2.22 mmol) and the reaction is allowed to stir at room temperature overnight. No conversion to pinacol rearrangement product observed so water and DCM added and the aqueous phase extracted with dichloromethane three times. The combined organic material is washed with brine and dried over magnesium sulfate. The solids are filtered and solvent removed in vacuo to afford a crude yellow residue. Aqueous layer is concentrated in vacuum. Both aqueous and organic layer combined and is taken up in TFA (3.5 mL, 0.1480 mmol) and placed in a vial that is sealed and stirred in a heating block at 70° C. for 3 h. The reaction is cooled to room temperature and solvent removed in vacuo. Preparatory HPLC (water with 0.1% TFA) afforded the product 2-(7-bromothieno[3,2-b]pyridin-3-yl)-3-hydroxycyclopent-2-en-1-one (2).
[Figure (not displayed)]
To a stirred solution of methyl 7-chlorothieno[3,2-b]pyridine-3-carboxylate (1, 15.0 g, 65.88 mmol) in methanol, tetrahydrofuran and water (2:1:1, 225 mL) is added lithium hydroxide (13.82 g, 329.43 mmol) at 0° C. and reaction mixture is stirred at room temperature for 16 h. After completion, the solvents are concentrated under reduced pressure and the aqueous layer is acidified with 1 N aqueous hydrochloric acid solution up to pH-3. Solid precipitate obtained is filtered and washed with n-pentane to afford 7-chlorothieno[3,2-b]pyridine-3-carboxylic acid (2).
To a solution of 7-chlorothieno[3,2-b]pyridine-3-carboxylic acid (2, 12.20 g, 57.10 mmol) in N,N-dimethylformamide (50 mL) is added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (32.5 g, 85.65 mmol) and reaction mixture is stirred for 10 min. The reaction mixture is then cooled to 0° C. and N,N-diisopropylethylamine (29.841 mL, 171.316 mmol) and ammonium chloride (15.2 g, 285.52 mmol) are added and reaction mixture is allowed to warm to room temperature and stirred for 16 h. After completion, the reaction is quenched with ice cold water and extracted with ethyl acetate. The organic layer is washed with cold water, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is triturated with pentane and dried to afford 7-chlorothieno[3,2-b]pyridine-3-carboxamide (3).
To a solution of 7-chlorothieno[3,2-b]pyridine-3-carboxamide (3, 10.0 g, 51.37 mmol) in N,N-dimethylformamide (100 mL) at 0° C. is added phosphorus oxytrichloride (48.0 mL, 513.76 mmol). The reaction is allowed to warm up to room temperature and stirred for 16 h. After completion, reaction mixture concentrated to dryness under reduced pressure. The reaction mixture is basified with saturated sodium bicarbonate solution up to pH-8 and extracted with ethyl acetate. The organic layer is washed with brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (40 g, RediSep column) using 0-20% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 7-chlorothieno[3,2-b]pyridine-3-carbonitrile (4).
To a solution of 7-chlorothieno[3,2-b]pyridine-3-carbonitrile (4, 8.0 g, 41.10 mmol), and (5-chloro-2-hydroxyphenyl)boronic acid (4a, 14.1 g, 82.20 mmol) in 1,4-dioxane (120.0 mL) is added 2 M solution of potassium carbonate (14.2 g, 102.7 mmol) reaction mixture is degassed with argon gas for 10 min. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (3.0 g, 4.11 mmol) is then added to reaction mixture and reaction mixture is stirred at 110° C. for 2 h. After completion, reaction mixture is cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer is washed with brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 0-50% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 7-(5-chloro-2-hydroxyphenyl)thieno[3,2-b]pyridine-3-carbonitrile (5).
To a solution of 7-(5-chloro-2-hydroxyphenyl)thieno[3,2-b]pyridine-3-carbonitrile (5, 5.1 g, 17.78 mmol) in N,N-dimethylformamide (50.0 mL) is added sodium azide (5.8 g, 88.93 mmol) at room temperature and the reaction mixture is heated to 110° C. for 36 h. After completion, reaction mixture is concentrated to dryness under reduced pressure. The crude product obtained is triturated with n-pentane to afford 2-(3-(1H-tetrazol-5-yl)thieno[3,2-b]pyridin-7-yl)-4-chlorophenol (6).
[Figure (not displayed)]
To a solution 2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (6, 0.20 g, 0.79 mmol) in N,N-dimethylformamide (5 mL), potassium carbonate (0.33 g, 2.37 mmol) is added at room temperature. After 10 min, 2-bromo-1-(2-bromoethoxy)-4-chlorobenzene (9, 0.25 g, 0.79 mmol) is added and stirred for 16 h at room temperature. After completion, the reaction mixture is poured into water and extracted with ethyl acetate. Combined organic layer is washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude; the crude compound is purified by flash column chromatography (using 10-70% ethyl acetate in hexanes) to afford 3-(2-(2-bromo-4-chloro-phenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (10).
[Figure (not displayed)]
A solution of 3-(2-(2-bromo-4-chlorophenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (10, 1.8 g, 3.71 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (11, 1.13 g, 4.45 mmol) and potassium acetate (0.73 g, 7.42 mmol) in 1,4-dioxane (35 mL) is degassed using argon gas for 10 min. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride (0.217 g, 0.296 mmol) is added and the reaction mixture is degassed for another 10 min. The reaction mixture is heated and stirred at 90° C. for 6 h. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude compound is purified by flash column chromatography 40% ethyl acetate in hexanes as eluent to afford 3-(2-(4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (12).
To a solution methyl 3-bromo-2-iodobenzoate (13, 2.0 g, 5.88 mmol) N,N-dimethylformamide (20 mL), copper(I) cyanide (0.58 g, 6.47 mmol) is added and heated at 60° C. for 4 h. After completion, the reaction mass is diluted with water (100 mL) and extracted with ethyl acetate. Combined organic layer are washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude. The crude compound is purified by flash column chromatography (using 0-10% ethyl acetate in hexane) to afford methyl 3-bromo-2-cyanobenzoate (14).
To a solution of 3-(2-(4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (12, 0.40 g, 0.75 mmol) and methyl 3-bromo-2-cyanobenzoate (14, 0.215 g, 0.90 mmol) in 1,4-dioxane (8 mL) and water (2 mL), potassium carbonate (0.313 g, 2.25 mmol) is added at room temperature. The reaction mass is degassed by purging argon gas through the reaction mass for 10 min. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride (0.055 g, 0.075 mmol) is added under argon atmosphere, heated and stirred the reaction mixture at 90° C. for 3 h. After completion, the reaction mass is diluted with water, extracted with ethyl acetate; combined organic layer is washed with water, brine and dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude. The crude compound is purified by flash column chromatography (using 0-50% ethyl acetate in hexane) to afford methyl 5′-chloro-2-cyano-2′-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-[1,1′-biphenyl]-3-carboxylate (15).
[Figure (not displayed)]
To a stirred solution of methyl 5-chloro-7-[5-chloro-2-[2-[5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3-yl]ethoxy]phenyl]thieno[3,2-b]pyridine-3-carboxylate (0.050 g, 0.079 mmol) in N-methyl-2-pyrrolidone and water (9:1, 2 mL) in a microwave vial, zinc cyanide (0.011 g, 0.095 mmol) and zinc dust (0.030 mg, 0.034 mmol) are added and the mixture is degassed with argon for 30 min. After adding 1,1′-bis(diphenylphosphino)ferrocene (0.0131 g, 0.023 mmol) and tris(dibenzylideneacetone)dipalladium(0) (10.8 mg, 0.012 mmol), the vial is sealed and then placed in a preheated heating block at 80° C. for 30 min. After completion of the reaction, the reaction mixture loaded on the Isco silica column. Purification by column chromatography eluting with 0 to 5% methanol/dichloromethane to afford methyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-cyanothieno[3,2-b]pyridine-3-carboxylate (2).
To a solution of methyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-cyanothieno[3,2-b]pyridine-3-carboxylate (2, 25.0 mg, 0.040 mmol) in 1,2-dichloroethane (2 mL), trimethyltin hydroxide (0.029 g, 0.160 mmol) is added at room temperature. The reaction mixture is heated at 90° C. for 16 h. After completion of the reaction, the organic solvent is evaporated and the crude is diluted with 50% dimethyl sulfoxide/methanol. The crude product is purified by prep-HPLC to afford 5-carbamoyl-7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (Cpd. No. 445F).
[Figure (not displayed)]
To a solution of methyl 7-(2-(2-(5-bromo-6-iodo-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-5-chlorophenyl)thieno[3,2-b]pyridine-3-carboxylate (5, 0.20 g, 0.256 mmol) in N,N-dimethylformamide is added copper(I) cyanide (0.069 g, 0.770 mmol) and stirred at 85° C. for 2 h. After completion, the reaction mixture is cooled to room temperature and poured into ice-water. The precipitate formed is collected by filtration and dried. The solid is dissolved in 10% methanol in dichloromethane and passed through Celite bed. The filtrate is concentrated under reduced pressure to afford methyl 7-(5-chloro-2-(2-(5, 6-dicyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (6).
[Figure (not displayed)]
To a solution of tert-butyl 7-(2-(2-(6-bromo-5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 0.20 g, 0.273 mmol) in N-Methyl-2-pyrrolidone (5.0 mL) is added 1-methylpiperazine (1a, 0.06 mL, 0.546 mmol) and the reaction mixture is degassed by argon for 10 min. Then copper(I) iodide (0.005 g, 0.027 mmol) and 1,10-phenanthroline (0.009 g, 0.054 mmol) is added and reaction mixture is heated at 150° C. for 6 h. After completion reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. Crude compound obtained is purified by column chromatography using silica gel (100-200 mesh) and 3-4% methanol in dichloromethane to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-6-(4-methylpiperazin-1-yl)-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (2).
[Figure (not displayed)]
To a solution of tert-butyl 7-(2-(2-(6-bromo-5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 50 mg, 0.0681 mmol) and 3-fluoro-2-((tributylstannyl)methyl)pyridine (l a, 190 mg, 0.476 mmol) in N,N-dimethylformamide (2 mL), is added copper(II) oxide (11 mg, 0.136 mmol) at room temperature. The reaction mixture is purged with argon gas for 5 min, added bis(triphenylphosphine)palladium(II) dichloride (9.6 mg, 0.0136 mmol) and the vessel is then sealed, microwaved for 1 h at 150° C. After completion, the reaction mixture is then directly loaded on an Isco loading column. Purified by column chromatography using 5 to 80% ethyl acetate in hexane as eluent and product eluted around 60% ethylacetate/hexane. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-(5-chloro-2-(2-(5-cyano-6-((3-fluoropyridin-2-yl)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (2).
Compounds made using one or more of the general methods described above are shown in Table 2. Where provided, characterization data is to the right of the compounds.
TABLE 2
7-CF3-Thienylpyridine and Derivative Compounds
CompoundCharacterization
51[Figure (not displayed)]
MS (ESI) m/z 528.44 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.931 (s, 1H), 8.359 (s, 1H), 8.194 (s, 1H), 7.8409 (d, J = 11.6 Hz, 2H), 7.528 (d, J = 7.6 Hz, 1H), 7.412 (m, 2H), 7.278 (d, J = 2.6 Hz, 1H), 7.212 (d, J = 8.8 Hz, 1H), 4.359 (s, 4H), 2.208 (s, 3H)
58[Figure (not displayed)]
MS (ESI) m/z 553.34 [M + 1]+; UPLC: 98.94%; 1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 3.96, 1H), 8.36 (s, 1H), 8.22 (s, 1H), 7.43 (dd, J = 2.48, 8.88 Hz, 1H), 7.23-7.18 (m, 3H), 4.33 (m, 4H), 4.03 (s, 1H), 2.09 (s, 3H)
59[Figure (not displayed)]
MS (ESI) m/z 578.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.28 (s, 1H), 7.84-7.81 (m, 2H), 7.6-7.2 (m, 6H), 4.37 (s, 4H), 2.21 (s, 3H)
60[Figure (not displayed)]
MS (ESI) m/z 527.02 [M + 1]−. 1H NMR (400 MHz, DMSO-d6) δ 8.63 (bs, 1H), 8.37 (s, 1H), 8.19 (s, 1H), 7.98 (bs, 1H), 7.61 (bs, 1H), 7.48 (d, J = 8.68 Hz, 1H), 7.42 (s, 1H), 7.26 (d, J = 8.92 Hz, 1H), 4.39 (s, 4H), 2.20 (s, 3H)
61[Figure (not displayed)]
MS (ESI) m/z 585.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 8.84 (d, J = 4.76, 1H), 8.37 (d, J = 0.96 Hz, 1H), 8.26 (s, 1H), 8.00 (s, 1H), 7.59 (dd, J = 2.64, 8.92 Hz, 1H), 7.48 (d, J = 4.76 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 8.96, 1H), 4.42-4.23 (m, 4H), 1.74 (s, 3H)
65[Figure (not displayed)]
MS (ESI) m/z 621.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.7935 (d, J = 4.8 Hz, 1H), 8.568 (s, 1H), 8.338 (s, 1H), 8.236 (s, 1H), 7.610 (dd, J = 8.8 Hz, 1H), 7.487 (d, J = 4.8 Hz, 1H), 7.441 (d, J = 2.8 Hz, 1H), 7.372 (d, J = 9 Hz, 1H),6.687-6.429 (m, 1H), 4.431-4.355 (m, 4H)
120[Figure (not displayed)]
MS (ESI) m/z 579.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.48 Hz, 1H), 8.59 (s, 1H), 8.41 (s, 1H), 8.14 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 6.04 Hz, 2H), 7.56 (d, J = 4.48 Hz, 1H), 4.88 (s, 2H), 2.10 (s, 3H)
121[Figure (not displayed)]
MS (ESI) m/z 599.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 8.36 (s, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.60-7.57 (dd, J = 2.52 Hz, 1H), 7.41 (s, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.6 Hz, J = 4.48 Hz, 2H), 4.25 (t, J = 4.04 Hz, J = 5.0 Hz, 2H), 2.69 (s, 3H), 1.81 (s, 3H)
122[Figure (not displayed)]
MS (ESI) m/z 601.98 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 8.35 (s, 1H), 8.06 (s, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.88, 2.6 Hz, 1H), 7.29-7.22 (m, 4H), 4.35 (t, J = 4.4 Hz, 2H), 4.24 (t, J = 4.84 Hz, 2H), 1.77 (s, 3H)
145[Figure (not displayed)]
MS (ESI) m/z 524.41 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 8.37 (s, 1H), 8.19 (s, 1H), 7.8480-7.726 (m, 3H), 7.4848-7.454 (m, 3H), 7.36 (s, 1H), 6.43 (d, J = 15.68 Hz, 1H), 6.15 (d, J = 15.68 Hz, 1H), 4.83 (d, J = 3.4 Hz, 2H), 2.56 (s, 3H)
146[Figure (not displayed)]
MS (ESI) m/z 526.46 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (bs, 1H), 8.35 (d, J = 1.36 Hz, 1H), 8.177 (s, 1H), 7.767 (s, 1H), 7.744 (s, 1H), 7.58-7.557 (m, 1H), 7.467-7.382 (m, 3H), 7.229 (d, J = 6.4 Hz, 1H), 3.933 (t, J = 7.04 Hz, 2H), 2.611 (t, J = 8.44 Hz, 2H), 2.447 (s, 3H), 1.768 (m, 2H)
156[Figure (not displayed)]
MS (ESI) m/z 552.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.92 (bs, 1H), 8.34 (s, 1H), 8.18 (s, 1H), 7.83 (dd, J = 7.64, 1.0 Hz, 1H), 7.44-7.34 (m, 3H), 7.16-7.14 (m, 2H), 4.31 (bs, 4H), 3.73 (s, 1H), 1.98 (s, 3H)
158[Figure (not displayed)]
MS (ESI) m/z 572.49 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.36 (s, 1H), 8.21 (s, 1H), 7.63 (s, 1H), 7.58 (d, J = 8 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.429-7.401 (dd, J = 2.4 Hz, J′ = 8.72 Hz, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.21 (d, J = 8.8 Hz, 1H), 4.37 (s, 4H), 2.25 (s, 3H)
159[Figure (not displayed)]
MS (ESI) m/z 538 [M + 1]+. 1H NMR (400 MHz, DMSO-d6) δ 8.43 (s, 1H), 8.29 (s, 1H), 8.01 (s, 1H), 7.59 (bs, 1H), 7.38-7.36 (m, 1H), 7.32- 7.30 (m, 1H), 7.20 (d, J = 2.56 Hz, 2H), 7.16 (d, J = 8.76 Hz, 1H), 4.26 (s, 4H), 3.8 (s, 1H)
162[Figure (not displayed)]
MS (ESI) m/z 515.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 5.04 Hz, 1H), 8.43 (d, J = 1.08 Hz, 1H), 8.27 (s, 1H), 8.23 (s, 1H), 8.03 (s, 1H), 7.67-7.65 (dd, J = 1.52, 4.96 Hz, 1H), 7.49 (d, J = 2.72 Hz, 1H), 7.47 (s, 1H), 7.25 (d, J = 9.28 Hz, 1H), 4.40-4.37 (m, 4H)
164[Figure (not displayed)]
MS (ESI) m/z 571 [M + 1]; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.43 (d, J = 16.6 Hz, 2H), 8.11 (s, 1H), 7.79 (bs, 1H), 7.60 (s, 1H), 7.46 (m, 2H), 7.35 (m, 1H), 4.40 (s, 2H), 4.20 (s, 2H), 3.89 (s, 1H)
168[Figure (not displayed)]
MS (ESI) m/z 553.20 [M + 1]+. UPLC: 98.95%; 1H NMR (400 MHz, DMSO-d6) δ 13.65 (s, 1H), 8.37 (s, 1H), 8.19 (s, 1H), 8.08 (d, J = 7.68 1H), 7.78-7.76 (t, J = 7.76 Hz, 1H), 7.61 (d, J = 7.24 Hz, 1H), 7.49 (dd, J = 2.4, 8.84 Hz, 1H), 7.28 (d, J = 2.52 Hz, 1H), 7.25 (d, J = 8.92 Hz 1H), 4.32 (m, 4H), 1.95 (s, 3H)
169[Figure (not displayed)]
MS (ESI) m/z 554.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.77 (bs, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 7.71 (d, J = 7.32 Hz, 1H), 7.36-7.28 (m, 2H), 7.23 (d, J = 7.8 Hz, 1H), 7.10 (d, J = 9.56 Hz, 2H), 6.57-6.50 (q, J = 6.32, 11.64 Hz, 1H), 4.88 (d, J = 11.32 Hz, 1H), 4.64 (d, J = 17.52 Hz, 1H), 4.30 (s, 4H), 2.02 (s, 3H)
181[Figure (not displayed)]
MS (ESI) m/z 603.04 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.50 (s, 1H), 8.33 (s, 1H), 8.15 (s, 1H), 7.60-7.36 (m, 4H), 4.72 (d, J = 44 Hz, 2H), 4.39 (bs, 2H), 4.12 (bs, 2H)
182[Figure (not displayed)]
MS (ESI) m/z 546.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.40 (s, 1H), 8.30 (s, 1H), 7.87-7.83 (m, 2H), 7.55 (d, J = 7.50 Hz, 1H), 7.45-7.39 (m, 2H), 7.30 (d, J = 2.48 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 5.10 (d, J = 45 Hz, 2H), 4.39 (bs, 4H)
185[Figure (not displayed)]
MS (ESI) m/z 539.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.82 (s, 1H), 8.60 (s, 1H), 8.50 (s, 1H), 7.87-7.71 (m, 2H), 7.53-7.51 (d, J = 8 Hz, 1H), 7.43-7.37 (m, 2H), 7.35-7.20 (m, 2H), 4.53 (t, J = 4 Hz, 2H), 4.39 (t, J = 4 Hz, 2H)
186[Figure (not displayed)]
MS (ESI) m/z 530.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.43 (s, 1H), 8.08 (s, 1H), 7.88 (s, 1H), 7.73 (d, J = 7.2 Hz, 1H), 7.65 (s, 2H), 7.41-7.33 (m, 3H), 7.22 (d, J = 8.72, 1H), 4.30-4.27 (t, J = 6 Hz, 2H), 4.22-4.20 (t, J = 5.54 Hz, 2H)
187[Figure (not displayed)]
MS (ESI) m/z 548.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.47 (s, 1H), 8.29 (s, 1H), 7.88 (s, 1H), 7.77 (d, J = 7.50 Hz, 1H), 7.59 (d, J = 7.90 Hz, 1H), 7.42-7.38 (m, 2H), 7.31 (d, J = 2.48 Hz, 1H), 7.22 (d, J = 9.0 Hz, 1H), 4.52 (d, J = 4.72 Hz, 2H), 4.38 (d, J = 4.8 Hz, 2H)
199[Figure (not displayed)]
MS (ESI) m/z 584.69 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 1H), 8.72 (d, 4.08 Hz, 1H), 8.29 (s, 1H), 8.08 (s, 1H), 7.70 (s, 1H), 7.58 (dd, J = 2.32, 8.52 Hz, 1H), 7.40 (d, J = 2.36 Hz, 1H), 7.35 (d, J = 8.96 Hz, 2H), 4.42 (s, 2H), 4.26 (s, 2H), 1.81 (s, 3H)
201[Figure (not displayed)]
MS (ESI) m/z 585.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.04 (b, 1H), 8.30 (s, 1H), 8.25 (d, J = 5.56 Hz, 1H), 7.96 (d, J = 6.4 Hz, 2H), 7.60-7.58 (m, 2H), 7.50 (dd, J = 8.8 Hz, 1H), 7.30 (d, J = 8.84 Hz, 1H), 4.45 (t, J = 4.72 Hz, 2H), 4.36 (t, J = 4.6 Hz, 2H), 2.18 (s, 1H)
202[Figure (not displayed)]
MS (ESI) m/z 599.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 8.66 (d, 4.56 Hz, 1H), 8.37 (s, 1H), 8.17 (s, 1H), 7.56 (m, 2H), 7.40 (d, J = 2.44 Hz, 1H), 7.33 (d, J = 9.04 Hz, 1H), 7.26 (d, J = 4.6 Hz, 1H), 4.38 (s, 2H), 4.25 (s, 2H), 3.84 (s, 2H), 1.78 ( s, 3H)
203[Figure (not displayed)]
MS (ESI) m/z 589.91 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.88 (s, 1H), 8.29 (s, 1H), 8.04 (s, 1H), 8.01 (s, 1H), 7.92 (s, 1H), 7.48- 7.44 (m, 2H), 7.29 (d, J = 8.8 Hz, 1H), 4.50 (m, 2H), 4.25 (s, 2H), 2.08 (s, 3H)
205[Figure (not displayed)]
MS (ESI) m/z 599.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.96 Hz, 1H), 8.38 (s, 1H), 7.98 (s, 1H), 7.60 (dd, J = 8.88, 2.6 Hz, 1H), 7.53 (d, J = 4.88 Hz, 1H), 7.43 (d, J = 2.56 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.43 (s, 2H), 4.27 (s, 2H), 2.34 (s, 3H), 1.85 (s, 3H)
206[Figure (not displayed)]
MS (ESI) m/z 619.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.64 Hz, 1H), 8.36 (s, 1H), 8.07 (s, 1H), 7.60 (d, J = 8.84 Hz, 1H), 7.52 (d, J = 4.4 Hz, 1H), 7.41 (s, 1H), 7.34 (d, J = 8.92 Hz, 1H), 4.44 (s, 2H), 4.28 (s, 2H), 1.81 (s, 3H)
210[Figure (not displayed)]
MS (ESI) m/z 610.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.82 (d, J = 4.64 Hz, 1H), 8.41 (d, J = 9.8 Hz, 2H), 7.6 (dd, J = 8.92, 2.48 Hz, 1H), 7.45 (dd, J = 9.68, 4.72 Hz, 2H), 7.37 (d, J = 8.88 Hz, 1H), 4.42 (t, J = 5.04 Hz , 2H), 4.27 (t, J = 5.2 Hz, 2H), 1.96 (s, 3H)
214[Figure (not displayed)]
MS (ESI) m/z 609.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.86 (d, J = 4.6 Hz, 1H), 8.16 (s, 1H), 8.11 (s, 1H), 7.60 (d, J = 8.96 Hz, 1H), 7.49 (d, J = 4.44 Hz, 1H), 7.42 (s, 1H), 7.36 (d, J = 9.04, 1H), 4.42 (bs, 2H), 4.28 (bs, 2H), 1.74 (s, 3H)
215[Figure (not displayed)]
MS (ESI) m/z 585 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.33 (s, 1H), 8.38 (s, 2H), 7.98 (s, 1H), 7.64 (dd, J = 8.8, 2.4 Hz, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.38 (d, J = 9.2 Hz, 1H), 4.45 (s, 2H), 4.27 (s, 2H), 1.77 (s, 3H)
225[Figure (not displayed)]
MS (ESI) m/z 585.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 8.59 (d, J = 5.56 Hz, 1H), 8.35-8.32 (m, 2H), 8.05 (s, 1H), 7.93 (s, 1H), 7.55 (dd, J = 9.0, 2.56 Hz, 1H), 7.33-7.30 (m, 1H), 4.38 (s, 2H), 4.22 (s, 2H), 1.69 (s, 3H)
226[Figure (not displayed)]
MS (ESI) m/z 585.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 8.38 (s, 1H), 8.18 (s, 1H), 7.97 (t, J = 6.30 Hz, 2H), 7.55-7.52 (dd, J = 2.24, 2.32 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.30- 7.25 (m, 2H), 4.45-4.29 (m, 4H), 1.98 (s, 3H)
227[Figure (not displayed)]
MS (ESI) m/z 551.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.96 Hz, 1H), 8.38 (s, 1H), 8.32 (s, 1H), 8.01 (s, 1H), 7.55 (t, J = 7.16 Hz, 1H), 7.50 (d, J = 4.48 Hz, 1H), 7.34 (t, J = 5.6 Hz, 2H), 7.16 (t, J = 7.40 Hz, 1H), 4.41 (s, 2H), 4.27 (s, 2H), 1.80 (s, 3H)
246[Figure (not displayed)]
MS (ESI) m/z 603.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.84 Hz, 1H), 8.64 (s, 1H), 8.40 (d, J = 9.16 Hz, 1H), 7.60 (dd, J = 8.92 Hz, 2.6 Hz, 1H), 7.49 (d, J = 4.84 Hz, 1H), 7.45 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 8.96 Hz, 1H), 4.44 (t, J = 4.8 Hz, 2H), 4.29 (t, J = 4.64 Hz, 2H), 1.99 (s, 3H)
255[Figure (not displayed)]
MS (ESI) m/z 581.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.16 (bs, 1H), 8.83 (s, 1H), 7.77 (d, J = 4.4 Hz, 1H), 8.35 (s, 1H), 8.14 (s, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.53 (s, 1H), 7.42 (d, J = 4.4 Hz, 1H), 6.50-6.44 (m, 1H), 5.98 (d, J = 16.0, 1H), 4.73 (d, J = 4.0, 2H), 2.38 (s, 3H)
259[Figure (not displayed)]
MS (ESI) m/z 586.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.80 (d, J = 4.92 Hz, 1H), 8.39 (d, J = 1.12 Hz, 1H), 8.35 (d, J = 2.80 Hz, 1H), 8.25 (s, 1H), 7.98 (d, J = 2.80 Hz, 1H), 7.49 (d, J = 4.88 Hz, 1H), 4.53 (t, J = 5.4 Hz, 2H), 4.41 (t, J = 5.2 Hz, 2H), 2.62 (s, 3H)
261[Figure (not displayed)]
MS (ESI) m/z 644.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83-8.79 (m, 3H), 8.29 (s, 1H), 8.22 (s, 1H), 7.93 (s, 1H), 7.84 (d, J = 5.68 Hz, 2H), 7.59 (dd, J = 2.56, J = 8.84 Hz, 1H), 7.51 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.60 Hz, 1H), 7.34 (d, J = 8.96 Hz, 1H) 4.38 (t, J = 5.76 Hz, 2H), 4.22 (t, J = 4.60 Hz, 2H), 1.69 (s, 3H)
265[Figure (not displayed)]
MS (ESI) m/z 591.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (bs, 1H), 8.9 (s, 1H), 8.28 (s, 1H), 8.16 (s, 1H), 7.68 (d, J = 2.4 Hz, 1H), 7.6 (dd, J = 8.8, 2.3 Hz, 1H), 7.5 (d, J = 9.0 Hz, 1H), 4.76 (t, J = 5.2 Hz, 2H), 4.57 (t, J = 3.6 Hz, 2H), 2.56 (s, 3H)
266[Figure (not displayed)]
MS (ESI) m/z 619.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.64 Hz, 1H), 8.36 (s, 1H), 8.07 (s, 1H), 7.60 (d, J = 8.84 Hz, 1H), 7.52 (d, J = 4.4 Hz, 1H), 7.41 (s, 1H), 7.34 (d, J = 8.92 Hz, 1H), 4.44 (s, 2H), 4.28 (s, 2H), 1.81 (s, 3H)
267[Figure (not displayed)]
MS (ESI) m/z 609.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.04 (bs, 1H), 8.88 (d, J = 4.8 Hz, 1H), 8.30 (d, J = 1.2 Hz, 1H), 8.03 (d, J = 1.4 Hz, 1H), 7.61-7.56 (m, 2H), 7.42 (d, J = 2.8 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.91 (s, 1H), 4.44 (t, J = 4.4 Hz, 2H), 4.26 (d, J = 4.4 Hz, 2H), 1.73 (s, 3H)
27[Figure (not displayed)]
MS (ESI) m/z 586.17 [M + 1]+. 1H NMR (400 MHz, DMSO-d6) δ 13.95 (bs, 1H), 8.98 (d, J = 4.4 Hz, 1H), 8.38 (s, 1H), 8.11 (s, 1H), 7.66 (d, J = 4.0 Hz, 1H), 7.60 (d, J = 9.6 Hz, 1H) 7.49 (s, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.45 (s, 2H), 4.28 (s, 2H), 1.74 (s, 3H)
275[Figure (not displayed)]
MS (ESI) m/z 601.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 8.85 (d, J = 4.80 Hz, 1H), 8.39 (s, 1H), 7.89 (s, 1H), 7.60 (dd, J = 8.88, 2.36 Hz, 1H), 7.50 (d, J = 4.80 Hz, 1H), 7.42 (d, J = 2.44 Hz, 1H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 5.28 Hz, 2H). 4.23 (t, J = 4.40 Hz, 2H), 1.71 (s, 3H)
285[Figure (not displayed)]
MS (ESI) m/z 552.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.91 (d, J = 4.8 Hz, 1H), 8.79 (d, J = 6.2 Hz, 1H), 8.64 (s, 1H), 8.40 (s, 1H), 8.34 (s, 1H), 8.05 (s, 1H), 7.61 (d, J = 3.1 Hz, 1H), 7.55 (d, J = 4.7 Hz, 1H), 4.62 (t, J = 4.2 Hz, 2H), 4.31 (t, J = 4.7 Hz, 2H), 1.75 (s, 3H)
287[Figure (not displayed)]
MS (ESI) m/z 576.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.28 (bs, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.38 (s, 1H), 8.26 (s, 1H), 8.05 (dd, J = 8.6, 2.0 Hz, 1H), 8.01 (s, 1H), 7.89 (d, J = 2.0 Hz, 1H), 7.52 (d, J = 3.4 Hz, 1H), 7.5 (s, 1H), 4.51 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 5.9 Hz, 2H), 1.7 (s, 3H)
289[Figure (not displayed)]
MS (ESI) m/z 594.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 ( d, J = 4.5 1H), 8.39 (s, 1H), 8.28 (s, 1H), 8.00 (d, J = 8.52, 2H), 7.63 (d, J = 11.4 Hz, 1H), 7.49 (d, J = 4.28 Hz, 1H), 4.527 (s, 2H), 4.26 (s, 2H), 1.683 (s, 3H)
291[Figure (not displayed)]
MS (ESI) m/z 577.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.91 (d, J = 4.72 Hz, 1H), 8.87 (s, 1H), 8.39 (s, 1H), 8.35 (s, 1H), 8.17 (s, 1H), 8.05 (s, 1H), 7.54 (d, J = 4.72 Hz, 1H), 4.66 (s, 2H), 4.27 (s, 2H), 1.79 (s, 3H)
292[Figure (not displayed)]
MS (ESI) m/z 577.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 8.87 (s, 1H), 8.38 (s, 1H), 8.27 (d, J = 8.7 Hz, 1H), 8.22 (s, 1H), 8.1 (d, J = 4.9 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 4.68 (t, J = 4.2 Hz, 2H), 4.55 (t, J = 4.4 Hz, 2H), 2.37 (s, 3H)
294[Figure (not displayed)]
MS (ESI) m/z 603.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.84 Hz, 1H), 8.45 (s, 1H), 8.37 (d, J = 5.28 Hz, 1H), 7.60 (dd, J = 8.56, 6.72, Hz, 1H), 7.49 (d, J = 4.56 Hz 1H), 7.43 (d, J = 2.04 Hz, 1H), 7.37 (d, J = 8.88 Hz, 1H), 4.42 (t, J = 4.90, 2H), 4.27 (t, J = 4.40 Hz, 2H), 1.86 (s, 3H)
295[Figure (not displayed)]
MS (ESI) m/z 634.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6), 68.76 (d, J = 2.68 Hz 1H), 8.35 (s, 1H), 8.10 (s, 1H), 7.74 (s, 1H), 7.58 (dd, J = 9.24, 2.81 Hz, 1H), 7.42 (d, J = 2.80 Hz, 1H), 7.40 (d, J = 4.40 Hz, 1H), 7.34 (d, J = 8.96 Hz, 1H), 4.45-4.37 (m, 2H), 4.30-4.22 (m, 2H), 1.82 (s, 3H)
296[Figure (not displayed)]
MS (ESI) m/z 599.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 8.36 (s, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.60-7.57 (dd, J = 2.52, 8.8 Hz, 1H), 7.41 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 5 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 2.69 (s, 3H), 1.82 (s, 3H)
299[Figure (not displayed)]
MS (ESI) m/z 585.17 [M + 1]+. 1H NMR (400 MHz, DMSO-d6) δ 14.22 (bs, 1H), 8.37 (s, 1H), 8.34 (d, J = 4.8 Hz, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.47-7.44 (m, 2H), 7.38 (d, J = 2.4 Hz, 1H), 7.25 (d, J = 9.2 Hz, 1H), 4.34 (t, 4.8 Hz, 2H), 4.25 (t, J = 4.4, 2H), 1.97 (s, 3H)
300[Figure (not displayed)]
MS (ESI) m/z 568.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 8.33 (s,1H), 8.20 (s, 1H), 8.06 (s, 1H), 7.61 (d, J = 7.28 Hz, 1H), 7.51 (d, J = 7.56 Hz, 1H), 7.47 (d, J = 2.32 Hz, 1H), 7.43 (d, J = 2.2 Hz, 1H), 7.28 (d, J = 8.8 Hz, 1H), 6.97 (t, J = 7.56 Hz, 1H,), 4.43 (s, 2H), 4.32 (s,2H), 2.10 (s, 3H)
301[Figure (not displayed)]
MS (ESI) m/z 583.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.46 (bs, 1H), 8.35 (s, 1H), 7.94 (s, 1H), 7.79 (s, 1H), 7.55 (d, J = 7.32 Hz, 1H), 7.49 (dd, J = 8.80, 2.68 Hz, 1H), 7.32-7.27 (m, 3H), 6.89 (t, J = 7.64 Hz, 1H), 4.30 (t, J = 5.08 Hz, 2H), 4.16 (t, J = 5.12 Hz, 2H), 1.92 (s, 3H)
314[Figure (not displayed)]
MS (ESI) m/z 585.94 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.25 (s, 1H), 9.18 (s, 1H), 8.33 (s, 1H), 8.24 (s, 1H), 7.97 ( s, 1H), 7.62 (dd, J = 8.8, 2.7 Hz, 1H), 7.49 (d, J = 2.32 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.44 (t, J = 4.96 Hz, 2H), 4.27 (t, J = 4.96 Hz, 2H), 1.71 (s, 3H)
315[Figure (not displayed)]
MS (ESI) m/z 591.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 ( s, 1H), 8.33 (s, 1H), 8.11 (s, 1H), 8.01 (s, 1H), 7.67 (d, J = 2.64 Hz, 1H), 7.59 (dd, J = 8.92, 2.68 Hz, 1H), 7.38 (d, J = 9 Hz, 1H), 4.60 (t, J = 5.24 Hz, 2H), 4.37 (t, J = 5.36 Hz, 2H), 2.14 (s, 3H)
319[Figure (not displayed)]
MS (ESI) m/z 585.2 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO)/ppm = 13.31 (bs, 1H), 9.59 (s, 1H), 8.37 (s, 1H), 8.34 (d, J = 1.9 Hz, 1H), 7.95-7.94 (m, 1H), 7.91 (s, 1H), 7.54 (dd, J = 8.9, 2.6 Hz, 1H), 7.38 (d, J = 2.6 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H), 4.36 (t, J = 4.7 Hz, 2H), 4.21 (t, J = 4.7 Hz, 2H), 1.70 (s, 3H)
320[Figure (not displayed)]
MS (ESI) m/z 582.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) / ppm = 8.49 (d, J = 5.1 Hz, 1H), 8.39 (d, J = 1.5 Hz, 1H), 8.15-8.02 (m, 2H), 7.60 (dd, J = 9.1, 2.6 Hz, 1H), 7.41 (d, J = 2.6 Hz, 1H), 7.30 (d, J = 9.1 Hz, 1H), 7.34-7.20 (m, 1H), 4.46-4.33 (m, 2H), 4.28- 4.20 (m, 2H), 3.16 (s, 3H), 1.66 (s, 3H)
321[Figure (not displayed)]
MS (ESI) m/z 700.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 8.87-8.81 (m, 1H), 8.24-8.17 (m, 1H), 7.98 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (dd, J = 4.9, 2.0 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.77-4.71 (m, 1H), 4.66-4.59 (m, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.32-4.11 (m, 6H), 3.70-3.53 (m, 2H), 3.23- 3.11 (m, 2H), 1.81 (s, 3H)
322[Figure (not displayed)]
[0503] MS (ESI) m/z 567.2 [M + 1]+; 1H NMR (400 MHz, d6-DMSO) δ/ppm = 11.04 (d, J = 3.2 Hz, 1H), 8.38-8.37 (m, 1H), 8.10-8.08 (m, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.45 (dd, J = 8.9 Hz, 2.8 Hz, 1H), 7.25-7.15 (m, 4H), 7.02 (dd, J = 7.2, 1.2 Hz, 1H), 4.40-4.35 (m, 2H), 4.22- 4.18 (m, 2H), 1.61 (s, 3H)
323[Figure (not displayed)]
MS (ESI) m/z 568.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 13.49 (b, 1H), 8.59 (d, J = 5.6 Hz, 1H), 8.40-8.39 (m, 1H), 8.07- 8.05 (m, 1H), 7.87-7.77 (m, 1H), 7.62 (dd, J = 8.9, 2.6 Hz, 1H), 7.60-7.49 (m, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.34 (d, J = 8.9 Hz, 1H), 4.45 (t, J = 4.6 Hz, 2H), 4.25 (t, J = 4.6 Hz, 2H), 1.76 (s, 3H)
324[Figure (not displayed)]
MS (ESI) m/z 569.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.80 (s, 1H), 8.65 (d, J = 4.9 Hz, 1H), 8.53 (d, J = 2.7 Hz, 1H), 8.33 (bd, J = 1.7 Hz, 1H), 8.15-8.14 (m, 1H), 7.69 (d, J = 4.9 Hz, 1H), 7.43 (dd, J = 8.9, 2.7 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H), 4.55-4.52 (m, 4H), 2.45 (s, 3H)
325[Figure (not displayed)]
MS (ESI) m/z 569.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.98-8.90 (m, 1H), 8.54-8.45 (m, 1H), 8.36-8.31 (m, 1H), 8.23-8.18 (m, 1H), 7.64-7.51 (m, 3H), 7.34-7.27 (m, 1H), 4.43-4.34 (m, 2H), 4.34- 4.23 (m, 2H), 1.77 (s, 3H)
326[Figure (not displayed)]
[0506] MS (ESI) m/z 535.1 [M + 1]+
327[Figure (not displayed)]
MS (ESI) m/z 616.4 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.33 (bd, J = 1.7 Hz, 1H), 8.24 (dd, J = 7.8, 0.9 Hz, 1H), 7.95 (s, 1H), 7.76 (dd, J = 7.8, 7.8 Hz, 1H), 7.50 (dd, J = 8.9, 2.6 Hz, 1H), 7.45 (bd, J = 7.8 Hz, 1H), 7.23-7.20 (m, 2H), 7.14 (s, 1H), 4.36-4.21 (m, 4H), 1.84 (s, 3H)
328[Figure (not displayed)]
MS (ESI) m/z 549.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.39 (bd, J = 1.7 Hz, 1H), 8.24-8.22 (m, 1H), 7.01-6.87 (m, 3H), 4.52 (t, J = 4.8 Hz, 2H), 4.35 (t, J = 4.8 Hz, 2H), 3.22-3.16 (m, 2H), 2.80 (s, 3H), 2.50-2.43 (m, 2H), 2.13-2.09 (m, 2H), 1.74-1.57 (m, 3H), 1.27-1.11 (m, 2H)
329[Figure (not displayed)]
MS (ESI) m/z 615.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.36 (bd, J = 1.6 Hz, 1H), 8.12 (s, 1H), 8.01-8.00 (m, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.33 (d, J = 8.9 Hz, 1H), 6.90 (d, J = 0.3 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 1H), 4.03 (s, 3H), 1.87 (s, 3H)
330[Figure (not displayed)]
MS (ESI) m/z 613.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.37 (bs, 1H), 8.24 (s, 1H), 7.95 (bs, 1H), 7.60 (dd, J = 8.8, 2.6, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.41 (bt, 2H), 4.25 (bt, 2H), 3.01 (q, J = 7.6 Hz, 2H), 1.78 (s, 3H), 1.34 (t, J = 7.6 Hz, 3H)
331[Figure (not displayed)]
MS (ESI) m/z 601.6 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 10.48 (s, 1H), 8.37-8.36 (m, 1H), 7.95 (bs, 1H), 7.78 (bs, 1H), 7.56 (dd, J = 8.7, 2.6, 1H), 7.38 (d, J = 2.6 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H), 6.36 (bs, 1H), 4.41 (bt, 2H), 4.32 (bt, 2H), 2.15 (s, 3H)
332[Figure (not displayed)]
MS (ESI) m/z 615.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 13.35 (b, 1H), 8.32 (d, J = 1.2 Hz, 1H), 8.06-8.04 (m, 1H), 7.68 (s, 1H), 7.51 (dd, J = 8.8, 2.7 Hz, 1H), 7.32 (d, J = 2.7 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 6.35 (s, 1H), 4.35 (bt, 1H), 4.28 (bt, 1H), 3.65 (s, 3H), 2.06 (s, 3H)
333[Figure (not displayed)]
MS (ESI) m/z 616.2 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 12.89 (b, 1H), 8.35 (d, J = 1.5 Hz, 1H), 8.07 (bs, 1H), 7.77 (bs, 1H), 7.50 (dd, J = 8.9, 2.7 Hz, 1H), 7.30-7.26 (m, 2H), 7.19 (d, J = 6.0 Hz, 1H), 4.35 (bt, 2H), 4.25 (bt, 2H), 2.33 (s, 3H), 1.83 (s, 3H)
341[Figure (not displayed)]
MS (ESI) m/z 690.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.75 (d, J = 5.3 Hz, 1H), 8.28 (s, 1H), 8.06 (s, 1H), 7.60 (dd, J = 8.9, 2.8 Hz, 1H), 7.59 (s, 1H), 7.52 (bd, J = 5.3 Hz, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.42 (t, J = 5.2 Hz, 2H), 4.28 (t, J = 5.2 Hz, 2H), 2.73 (s, 3H), 2.64 (s, 3H), 1.87 (s, 3H)
342[Figure (not displayed)]
MS (ESI) m/z 694.2 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.82 (d, J = 2.8 Hz, 1H), 8.60-8.59 (m, 1H), 8.28 (s, 1H), 8.11-8.06 (m, 1H), 8.07 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.43 (t, J = 4.9 Hz, 2H), 4.29 (t, J = 4.9 Hz, 2H), 2.73 (s, 3H), 1.89 (s, 3H)
343[Figure (not displayed)]
MS (ESI) m/z 694.5 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.85 (dd, J = 7.5, 5.8 Hz, 1H), 8.79 (d, J = 9.9 Hz, 1H), 8.35 (s, 1H), 8.12 (s 1H), 7.64 (dd, J = 9.8, 5.8 Hz 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.49-4.19 (m, 4H), 2.73 (s, 3H), 1.87 (s, 3H)
344[Figure (not displayed)]
MS (ESI) m/z 694.2 [M + 1]+; 1H-NMR (400 MHz, d6- DMSO) δ/ppm = 8.87 (s, 1H), 8.71 (d, J = 4.7 Hz, 1H), 8.34 (s, 1H), 8.14 (s, 1H), 7.74-7.70 (m, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 8.9 Hz, 1H), 4.48-4.20 (m, 4H), 2.72 (s, 3H), 1.87 (s, 3H)
347[Figure (not displayed)]
MS (ESI) m/z 682.5 [M + 1]+; 1H-NMR (400 MHz, d6- DMSO) δ/ppm = 9.32 (s, 1H), 8.71 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.42 (t, J = 4.7 Hz, 2H), 4.28 (t, J = 4.7 Hz, 2H), 2.72 (s, 3H), 1.88 (s, 3H)
348[Figure (not displayed)]
MS (ESI) m/z 682.4 [M + 1]+; 1H-NMR (400 MHz, d6- DMSO) δ/ppm = 8.74 (d, J = 1.7 Hz, 1H), 8.31 (s, 1H), 8.06 (s, 1H), 7.67 (d, J = 1.7 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 8.6 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 4.28 (t, J = 4.9 Hz, 2H), 2.74 (s, 3H), 1.86 (s, 3H)
349[Figure (not displayed)]
MS (ESI) m/z 704.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 8.28 (s, 1H), 8.08 (s, 1H), 7.83-7.77 (m, 1H), 7.60 (dd, J = 9.0, 2.8 Hz, 1H), 7.46 (s, 1H), 7.44 (d, J = 2.8 Hz, 1H), 7.43-7.38 (m, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.47-4.38 (m, 2H), 4.33-4.19 (m, 2H), 2.73 (s, 3H), 2.59 (s, 3H), 2.22 (s, 3H), 1.84 (s, 3H)
350[Figure (not displayed)]
MS (ESI) m/z 704.5 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) □/ppm = 8.47-8.37 (m, 1H), 8.29 (s, 1H), 8.08 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (s, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.43-7.39 (m, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.47-4.43 (m, 2H), 4.34-4.18 (m, 2H), 2.73 (s, 3H), 2.57 (s, 3H), 2.06 (s, 3H), 1.84 (s, 3H)
352[Figure (not displayed)]
MS (ESI) m/z 599.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.68 (d, J = 4.7 Hz, 1H), 8.38 (dd, J = 1.8, 0.6 Hz, 1H), 8.22 (dt, J = 1.8, 0.8 Hz, 1H), 7.53 (dd, J = 8.9, 2.7 Hz, 1H), 7.42 (s, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.29 (d, J = 9.0 Hz, 1H), 7.21 (d, J = 4.7 Hz, 1H), 5.43 (s, 1H), 4.37 (t, J = 4.9 Hz, 2H), 4.24 (t, J = 4.9 Hz, 2H), 1.75 (s, 6H), 1.65 (s, 3H)
354[Figure (not displayed)]
MS (ESI) m/z 615.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.87-8.84 (m, 2H), 7.61-7.57 (m, 2H), 7.53-7.51 (m, 2H), 7.38 (d, J = 9.0 Hz, 1H), 7.35 (s, 1H), 4.23 (t, J = 5.5 Hz, 2H), 3.74 (t, J = 5.4 Hz, 2H), 2.75 (s, 3H), 1.07 (s, 6H)
356[Figure (not displayed)]
MS (ESI) m/z 602.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.34 (s, 1H), 8.82 (d, J = 4.9 Hz, 1H), 8.45 (s, 1H), 8.37-8.36 (m, 1H), 8.05-8.04 (m, 1H), 7.95 (s, 1H), 7.52 (d, J = 4.9 Hz, 1H), 4.63 (t, J = 5.0 Hz, 2H), 4.31 (t, J = 5.0 Hz, 2H), 1.90 (s, 3H)
363[Figure (not displayed)]
MS (ESI) m/z 613.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.92 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 2.71 (s, 3H), 2.70 (s, 3H), 1.85 (s, 3H)
364[Figure (not displayed)]
MS (ESI) m/z 613.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.16 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 4.44 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 2.68 (s, 3H), 2.69-2.63 (m, 3H), 1.93 (s, 3H)
373[Figure (not displayed)]
MS (ESI) m/z 694.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.25 (d, J = 5.1 Hz, 1H), 7.98 (d, J = 5.3 Hz, 1H), 7.60 (dd, J = 8.9, 2.6 Hz, 1H), 7.44 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 5.95 (s, 1H), 4.41 (t, J = 5.4 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 4.13 (d, J = 17.4 Hz, 1H), 3.84 (d, J = 17.8 Hz, 1H), 3.02-2.88 (m, 5H), 2.73-2.66 (m, 5H), 1.87 (s, 3H)
374[Figure (not displayed)]
MS (ESI) m/z 626.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.15 (s, 1H), 7.83 (dt, J = 7.7, 1.5 Hz, 1H), 7.80 (t, J = 1.8 Hz, 1H), 7.50 (dt, J = 7.7, 1.6 Hz, 1H), 7.45- 7.38 (m, 2H), 7.28 (d, J = 2.7 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 3.85 (t, J = 12.3 Hz, 2H), 3.54 (d, J = 11.7 Hz, 2H), 3.19 (d, J = 12.8 Hz, 2H), 3.12-2.99 (m, 2H), 2.89 (s, 3H), 2.21 (s, 3H)
375[Figure (not displayed)]
MS (ESI) m/z 619.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.92-7.85 (m, 2H), 7.84 (t, J = 1.8 Hz, 1H), 7.54 (dt, J = 7.8, 1.6 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.43-7.37 (m, 3H), 7.29 (d, J = 2.6 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 4.40- 4.33 (m, 4H), 2.52 (s, 3H), 2.24 (s, 3H)
376[Figure (not displayed)]
MS (ESI) m/z 717.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.22 (s, 1H), 7.98 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 6.38 (tt, J = 53.3, 3.0 Hz, 1H), 4.42 (t, J = 5.1 Hz, 2H), 4.31-4.25 (m, 6H), 3.87 (td, J = 16.3, 3.0 Hz, 2H), 3.41 (s, 2H), 3.24 (s, 1H), 1.81 (s, 3H)
377[Figure (not displayed)]
MS (ESI) m/z 676.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.85-7.78 (m, 2H), 7.51 (dt, J = 7.7, 1.5 Hz, 1H), 7.44-7.37 (m, 2H), 7.28 (d, J = 2.7 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 6.38 (t, J = 54.0 Hz, 1H), 2.20 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
378[Figure (not displayed)]
MS (ESI) m/z 654.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.85-7.79 (m, 2H), 7.51 (dt, J = 7.7, 1.6 Hz, 1H), 7.44- 7.37 (m, 2H), 7.27 (d, J = 2.6 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 4.34 (s, 4H), 3.06-2.76 (m, 2H), 2.20 (s, 3H), 2.06 (s, 3H) Note: some aliphatic signals were very broad and could not be integrated
379[Figure (not displayed)]
MS (ESI) m/z 689.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.15 (s, 1H), 8.11 (dd, J = 5.6, 1.9 Hz, 1H), 7.87-7.79 (m, 3H), 7.51 (dt, J = 7.7, 1.6 Hz, 1H), 7.45-7.38 (m, 2H), 7.28 (d, J = 2.7 Hz, 1H), 7.21 (d, J = 8.9 Hz, 2H), 6.85 (t, J = 6.3 Hz, 1H), 4.35 (s, 4H), 2.20 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
380[Figure (not displayed)]
MS (ESI) m/z 689.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.51 (d, J = 2.9 Hz, 1H), 8.22 (d, J = 5.3 Hz, 1H), 8.15 (s, 1H), 8.08 (dd, J = 8.8, 2.8 Hz, 1H), 7.85 (dt, J = 7.7, 1.5 Hz, 1H), 7.83-7.78 (m, 2H), 7.51 (dt, J = 7.7, 1.6 Hz, 1H), 7.45-7.38 (m, 2H), 7.28 (d, J = 2.7 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 4.35 (s, 4H), 2.20 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
381[Figure (not displayed)]
MS (ESI) m/z 640.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.84 (dt, J = 7.7, 1.5 Hz, 1H), 7.80 (t, J = 1.8 Hz, 1H), 7.51 (dt, J = 7.7, 1.5 Hz, 1H), 7.45-7.38 (m, 2H), 7.27 (d, J = 2.6 Hz, 1H), 7.21 (d, J = 8.9 Hz, 1H), 4.35 (s, 4H), 2.92 (s, 3H), 2.19 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
382[Figure (not displayed)]
MS (ESI) m/z 688.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.87-7.80 (m, 2H), 7.52 (dt, J = 7.7, 1.5 Hz, 1H), 7.45-7.37 (m, 2H), 7.30- 7.19 (m, 4H), 7.05-6.99 (m, 2H), 6.83 (t, J = 7.3 Hz, 1H), 4.35 (s, 4H), 2.20 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
383[Figure (not displayed)]
MS (ESI) m/z 711.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.26 (s, 1H), 7.92 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.1 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 2.94 (s, 3H), 2.72 (s, 3H), 1.82 (s, 3H). Note: some aliphatic signals were very broad and could not be integrated
386[Figure (not displayed)]
MS (ESI) m/z 605.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J = 5.1 Hz, 2H), 8.29 (s, 1H), 7.86 (dt, J = 7.6, 1.6 Hz, 1H), 7.82 (t, J = 1.8 Hz, 1H), 7.55-7.50 (m, 3H), 7.47-7.39 (m, 2H), 7.28 (d, J = 2.7 Hz, 1H), 7.22 (d, J = 8.9 Hz, 1H), 4.43-4.31 (m, 4H), 2.24 (s, 3H)
387[Figure (not displayed)]
MS (ESI) m/z 689.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 7.4 Hz, 2H), 7.88 (s, 1H), 7.45-7.34 (m, 5H), 7.26 (d, J = 2.7 Hz, 1H), 7.19 (d, J = 8.9 Hz, 1H), 7.13 (d, J = 7.1 Hz, 2H), 4.31 (s, 4H), 3.85-3.49 (m, 8H), 2.20 (s, 3H)
388[Figure (not displayed)]
MS (ESI) m/z 605.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (dd, J = 4.9, 1.6 Hz, 1H), 8.62 (s, 1H), 8.28 (s, 1H), 7.91 (dt, J = 7.9, 1.9 Hz, 1H), 7.86 (dt, J = 7.6, 1.5 Hz, 1H), 7.82 (t, J = 1.8 Hz, 1H), 7.62 (dd, J = 7.8, 4.8 Hz, 1H), 7.53 (dt, J = 7.7, 1.5 Hz, 1H), 7.48- 7.38 (m, 2H), 7.28 (d, J = 2.6 Hz, 1H), 7.22 (d, J = 8.9 Hz, 1H), 4.42-4.32 (m, J = 2.5 Hz, 4H), 2.24 (s, 3H)
389[Figure (not displayed)]
MS (ESI) m/z 703.9 [M + 1]+;; 1H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.27 (s, 1H), 8.06 (s, 1H), 8.00 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.43 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 4.9 Hz, 2H), 2.73 (s, 3H), 2.64 (s, 3H), 2.42 (s, 3H), 1.88 (s, 3H)
398[Figure (not displayed)]
MS (ESI) m/z 656.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.16 (t, J = 5.4 Hz, 1H), 8.34 (d, J = 1.7 Hz, 1H), 8.14 (s, 1H), 8.05 (dd, J = 1.8, 0.8 Hz, 1H), 7.58 (dd, J = 8.9, 2.7 Hz, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 7.33 (s, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 4.21 (d, J = 5.4 Hz, 2H), 2.69 (s, 3H), 1.84 (s, 3H)
401[Figure (not displayed)]
MS (ESI) m/z 568.2 [M + H]+; 1H NMR (400 MHz, CD3OD) δ 8.16-8.13 (m, 1H), 8.05-8.02 (m, 1H), 7.97 (s, 1H), 7.90 (dd, J = 7.9, 1.3 Hz, 1H), 7.41 (dd, J = 8.8, 2.7 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 7.20 (dd, J = 7.4, 1.3 Hz, 1H), 7.19 (d, J = 8.9 Hz, 1H), 4.40-4.30 (m, 4H), 1.98 (s, 3H)
402[Figure (not displayed)]
MS (ESI) m/z 584.3 [M + H]+; 1H NMR (400 MHz, Methanol-d4) δ 8.52 (dd, J = 8.3, 1.1 Hz, 1H), 8.15 (dd, J = 1.8, 0.6 Hz, 1H), 8.01 (dd, J = 1.7, 0.8 Hz, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.2, 7.2 Hz, 1H), 7.45 (dd, J = 8.9, 2.7 Hz, 1H), 7.30-7.25 (m, 1H), 7.22 (s, 1H), 7.21-7.16 (m, 1H), 4.40 (t, J = 4.8 Hz, 2H), 4.31 (t, J = 4.8 Hz, 2H), 1.82 (s, 3H)
410[Figure (not displayed)]
MS (ESI) m/z 543.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 1.7 Hz, 1H), 8.17 (bs, 1H), 7.77 (bd, J = 1.6 Hz, 1H), 7.48 (bd, J = 1.4 Hz, 1H), 7.47 (dd, J = 8.9, 2.7 Hz, 1H), 7.36 (d, J = 2.7 Hz, 1H), 7.25 (d, J = 8.9 Hz, 1H), 4.39 (bs, 4H), 2.51 (s, 3H), 2.24 (s, 3H)
411[Figure (not displayed)]
MS (ESI) m/z 557.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 1.7 Hz, 1H), 8.20 (d, J = 1.7 Hz, 1H), 7.49 (dd, J = 8.9, 2.7 Hz, 1H), 7.46-7.40 (br, 2H), 7.37 (d, J = 2.7 Hz, 1H), 7.26 (d, J = 8.9 Hz, 1H), 4.49-4.35 (m, 4H), 3.86 (s, 2H), 2.53 (s, 3H), 2.31 (s, 3H)
414[Figure (not displayed)]
MS (ESI) m/z 583.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 1.8 Hz, 1H), 8.10 (br, 1H), 7.97 (s, 1H), 7.62 (dd, J = 8.9, 2.7 Hz, 1H), 7.53 (d, J = 2.7 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 7.15 (s, 1H), 4.37 (t, J = 4.9 Hz, 2H), 4.25 (t, J = 4.9 Hz, 2H), 2.59 (s, 3H), 1.85 (s, 3H)
415[Figure (not displayed)]
MS (ESI) m/z 599.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (bs, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.50 (bs, 1H), 7.42 (bs, 1H), 7.36 (d, J = 7.8 Hz), 4.40 (bs, 2H), 4.25 (bs, 2H), 2.72 (s, 3H), 1.76 (s, 3H)
416[Figure (not displayed)]
MS (ESI) m/z 599.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 4.6 Hz, 1H), 8.42 (s, 1H), 8.17 (s, 1H), 7.60 (dd, J = 9.4, 2.6 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.44 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 2.67 (s, 3H), 1.84 (s, 3H)
417[Figure (not displayed)]
MS (ESI) m/z 725.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 7.60 (dd, J = 8.8, 2.6 Hz, 1H), 7.44 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.0 Hz, 2H), 3.94 (s, 2H), 3.43-3.29 (m, 4H), 2.99-2.82 (m, 4H), 2.78 (d, J = 4.3 Hz, 3H), 2.70 (s, 3H), 2.31 (s, 3H), 1.91 (s, 3H)
421[Figure (not displayed)]
MS (ESI) m/z 690.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (dt, J = 4.8, 1.4 Hz, 1H), 8.08-7.99 (m, 2H), 7.65-7.53 (m, 3H), 7.45 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 4.28 (br, 2H), 2.72 (s, 3H), 2.48 (s, 3H), 1.94 (s, 3H)
422[Figure (not displayed)]
MS (ESI) m/z 668.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.92 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (dd, J = 4.3, 1.8 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 3.37-3.28 (m, 4H), 2.70 (s, 3H), 2.10-1.99 (m, 4H), 1.82 (s, 3H)
423[Figure (not displayed)]
MS (ESI) m/z 682.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.32 (s, 1H), 7.89 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 5.04 (br, 6H), 4.39 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 3.21 (br, 4H), 2.71 (s, 3H), 1.80 (s, 3H)
424[Figure (not displayed)]
MS (ESI) m/z 668.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.95 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 4.11-3.92 (m, 4H), 3.39 (br, 2H), 3.35-3.21 (m, 1H), 2.71 (s, 3H), 1.85 (s, 3H)
425[Figure (not displayed)]
MS (ESI) m/z 682.5 [M + 1]+; 1H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 8.12 (s, 1H), 7.47 (dd, J = 8.9, 2.6 Hz, 1H), 7.26 (s, 1H), 7.18 (s, 1H), 7.03 (d, J = 8.9 Hz, 1H), 4.56 (t, J = 9.0 Hz, 2H), 4.40 (t, J = 4.8 Hz, 2H), 4.29 (t, J = 4.9 Hz, 2H), 3.84 (t, J = 9.6 Hz, 2H), 3.49 (d, J = 6.6 Hz, 2H), 3.45-3.29 (m, 1H), 2.89 (s, 3H), 2.80 (s, 3H), 1.89 (s, 3H)
428[Figure (not displayed)]
MS (ESI) m/z 747.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.91 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 6.38 (br, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 5.0 Hz, 3H), 4.06-2.83 (br, 10H), 2.71 (s, 3H), 1.83 (s, 3H)
429[Figure (not displayed)]
MS (ESI) m/z 681.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (dd, J = 7.3, 2.1 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 5.92 (s, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.29-4.15 (m, 4H), 3.86 (m, 4H), 2.71 (s, 3H), 1.85 (s, 3H)
430[Figure (not displayed)]
MS (ESI) m/z 729.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.95 (t, J = 4.4 Hz, 1H), 4.82 (d, J = 4.6 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.65-3.03 (br, 10H), 2.72 (s, 3H), 1.85 (s, 3H)
431[Figure (not displayed)]
MS (ESI) m/z 683.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.50 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.40 (s, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.35 (t, J = 5.1 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 3.98 (dd, J = 11.3, 4.0 Hz, 2H), 3.43 (t, J = 11.3 Hz, 2H), 3.22 (m, 1H), 2.72 (s, 3H), 2.08 (s, 3H), 2.03-1.88 (m, 2H), 1.59 (d, J = 12.6 Hz, 2H)
433[Figure (not displayed)]
MS (ESI) m/z 712.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J = 2.4 Hz, 1H), 8.42 (s, 1H), 8.33 (td, J = 9.1, 2.4 Hz, 1H), 8.17 (s, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.44 (s, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.1 Hz, 2H), 2.70 (s, 3H), 1.84 (s, 3H)
434[Figure (not displayed)]
MS (ESI) m/z 708.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.15 (s, 1H), 7.89 (t, J = 8.9 Hz, 1H), 7.62-7.53 (m, 2H), 7.45 (s, 1H), 7.44 (d, J = 2.6, 0.9 Hz, 1H), 7.35 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.28 (d, J = 5.0 Hz, 2H), 2.71 (s, 3H), 2.52 (s, 3H), 1.82 (s, 3H)
437[Figure (not displayed)]
MS (ESI) m/z 705.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.27 (s, 1H), 8.10 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.43 (t, J = 5.1 Hz, 2H), 4.28 (tt, J = 9.5, 5.0 Hz, 2H), 2.74 (s, 3H), 2.71 (s, 3H), 2.23 (s, 3H), 1.85 (s, 3H)
442[Figure (not displayed)]
MS (ESI) m/z 691.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 2.1 Hz, 1H), 8.26 (s, 1H), 8.08 (s, 1H), 7.85 (d, J = 2.1 Hz, 1H), 7.60 (dd, J = 8.9, 2.6 Hz, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.43 (t, J = 5.0 Hz, 2H), 4.29 (t, J = 5.0 Hz, 2H), 2.77 (s, 3H), 2.73 (s, 3H), 1.89 (s, 3H)
443[Figure (not displayed)]
MS (ESI) m/z 604.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 4.8 Hz, 1H), 8.36-8.32 (m, 1H), 8.15-8.11 (m, 1H), 7.52 (dd, J = 8.9, 2.7 Hz, 1H), 7.38 (d, J = 2.7 Hz, 1H), 7.29 (d, J = 9.0 Hz, 1H), 7.23 (d, J = 4.8 Hz, 1H), 4.36 (t, J = 5.0 Hz, 2H), 4.25 (d, J = 5.0 Hz, 2H), 1.88 (s, 3H), 1.33 (s, 9H)
444[Figure (not displayed)]
MS (ESI) m/z 619.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J = 1.9 Hz, 1H), 8.22 (s, 1H), 7.97 (dd, J = 1.9, 0.8 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.31 (d, J = 9.0 Hz, 1H), 4.37 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 1.79 (s, 3H)
445[Figure (not displayed)]
MS (ESI) m/z 628.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.32 (d, J = 1.8 Hz, 1H), 8.25 (s, 1H), 8.01 (d, J = 3.1 Hz, 1H), 7.94 (dd, J = 1.8, 0.9 Hz, 1H), 7.89 (s, 2H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 4.37 (t, J = 5.0 Hz, 2H), 4.20 (t, J = 5.0 Hz, 2H), 1.65 (s, 3H)
446[Figure (not displayed)]
MS (ESI) m/z 610.7 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 1.1 Hz, 1H), 8.35 (d, J = 1.7 Hz, 1H), 8.01-7.97 (m, 2H), 7.58 (ddd, J = 9.1, 2.7, 1.0 Hz, 1H), 7.44 (dd, J = 2.6, 1.0 Hz, 1H), 7.33 (d, J = 9.0 Hz, 1H), 4.38 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 1.71 (s, 3H)
447[Figure (not displayed)]
MS (ESI) m/z 599.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37-8.31 (m, 1H), 7.97 (d, J = 1.3 Hz, 1H), 7.95 (dt, J = 1.8, 0.8 Hz, 1H), 7.55 (dd, J = 8.9, 2.7 Hz, 1H), 7.35-7.28 (m, 2H), 7.17 (d, J = 0.9 Hz, 1H), 4.36 (t, J = 5.0 Hz, 2H), 4.20 (t, J = 5.0 Hz, 2H), 2.65 (d, J = 0.7 Hz, 3H), 1.86 (s, 3H)
452[Figure (not displayed)]
MS (ESI) m/z 614.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.86 (s, 1H), 8.50-8.37 (m, 4H), 8.30 (s, 1H), 8.01 (s, 1H), 7.62 (dd, J = 8.9, 2.7 Hz, 1H), 7.57 (s, 1H), 7.40-7.35 (m, 2H), 4.44 (q, J = 6.1 Hz, 4H), 4.27 (t, J = 5.2 Hz, 2H), 1.77 (s, 3H)
453[Figure (not displayed)]
MS (ESI) m/z 552.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.18 (dd, J = 6.2, 0.7 Hz, H), 8.89-8.84 (m, 2H), 8.37-8.33 (m, 1H), 8.20 (dt, J = 1.8, 0.8 Hz, 1H), 8.07-8.03 (m, 1H), 7.66 (dd, J = 6.2, 0.8 Hz, 1H), 4.63 (t, J = 5.0 Hz, 2H), 4.53 (t, J = 5.0 Hz, 2H), 3.88 (s, 1H), 2.33 (s, 3H)
454[Figure (not displayed)]
MS (ESI) m/z 587.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.96 (s, 1H), 8.93 (d, J = 5.0 Hz, 1H), 8.39-8.37 (m, 1H), 8.26 (d, J = 5.0 Hz, 1H), 8.24 (dd, J = 1.7, 0.8 Hz, 1H), 4.77 (t, J = 5.1 Hz, 2H), 4.62 (t, J = 5.1 Hz, 2H), 2.53 (s, 3H)
455[Figure (not displayed)]
MS (ESI) m/z 578.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.92 (s, 2H), 8.35 (s, 1H), 8.20 (d, J = 4.9 Hz, 2H), 4.83 (s, 2H), 4.60 (s, 2H), 2.56 (2, 3H)
465[Figure (not displayed)]
LCMS: 704.5 [M + H]+; 1H NMR (400 MHz, DMSO- d6) δ 8.25 (s, 1H), 8.05 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.50-7.33 (m, 4H), 4.42 (t, J = 5.0 Hz, 2H), 4.28 (t, J = 5.0 Hz, 2H), 2.73 (s, 3H), 2.62 (s, 6H), 1.87 (s, 3H)
466[Figure (not displayed)]
LCMS: 704.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74-8.65 (m, 1H), 8.32 (s, 1H), 8.09 (s, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.41 (m, 3H), 7.37 (d, J = 9.0 Hz, 1H), 4.52-4.10 (m, 2H), 2.73 (s, 3H), 2.45-2.35 (m, 2H), 1.85 (s, 3H), 1.15 (t, J = 7.5 Hz, 3H)
468[Figure (not displayed)]
LCMS: 704.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 5.2 Hz, 1H), 8.29 (s, 1H), 8.06 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.57 (s, 1H), 7.52-7.47 (m, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.1 Hz, 2H), 4.29 (d, J = 5.2 Hz, 2H), 2.91 (q, J = 7.5 Hz, 2H), 2.73 (s, 3H), 1.87 (s, 3H), 1.29 (t, J = 7.6 Hz, 3H)
469[Figure (not displayed)]
LCMS: 704.5 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (s, 1H), 8.25 (s, 1H), 8.11 (s, 1H), 7.63-7.58 (m, 2H), 7.47 (s, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.43 (h, J = 5.9 Hz, 2H), 4.27 (dd, J = 11.3, 5.7 Hz, 1H), 2.74 (s, 3H), 2.64 (s, 3H), 2.08 (s, 3H), 1.84 (s, 3H)
470[Figure (not displayed)]
LCMS: 708.5 [M + H]+; 1H NMR (400 MHz, DMSO- d6) δ 8.70-8.65 (m, 1H), 8.27 (d, J = 0.9 Hz, 1H), 8.10 (s, 1H), 7.91 (dd, J = 9.0, 2.9 Hz, 1H), 7.60 (ddd, J = 8.9, 2.6, 1.0 Hz, 1H), 7.47-7.41 (m, 2H), 7.37 (d, J = 8.9 Hz, 1H), 4.43 (d, J = 4.8 Hz, 2H), 4.37-4.17 (m, 2H), 2.74 (d, J = 0.9 Hz, 3H), 2.21 (s, 3H), 1.86 (s, 3H)
471[Figure (not displayed)]
LCMS: 708.6 [M + H]+; 1H NMR (400 MHz, DMSO- d6); 1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 0.8 Hz, 1H), 8.30 (s, 1H), 8.11 (s, 1H), 7.61-7.57 (m, 1H), 7.55 (d, J = 5.6 Hz, 1H), 7.45-7.42 (m, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.54-4.10 (m, 1H), 2.72 (s, 3H), 2.58 (d, J = 1.0 Hz, 3H), 1.86 (s, 3H)
472[Figure (not displayed)]
LCMS: 708.6 [M + H]+; 1H NMR (400 MHz, DMSO- d6) δ 8.54 (d, J = 4.8 Hz, 1H), 8.33 (s, 1H), 8.12 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.51 (t, J = 5.1 Hz, 1H), 7.46-7.41 (m, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.57-4.15 (m, 2H), 2.72 (s, 3H), 2.56 (d, J = 3.0 Hz, 3H), 1.87 (s, 3H)
473[Figure (not displayed)]
LCMS: 708.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 8.17 (dt, J = 4.7, 1.4 Hz, 1H), 7.99 (s, 1H), 7.77 (ddd, J = 9.8, 8.3, 1.3 Hz, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.45-7.40 (m, 2H), 7.36 (dt, J = 8.4, 1.9 Hz, 2H), 4.66 (s, 2H), 4.42 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 2.70 (s, 3H), 1.86 (s, 3H)
483[Figure (not displayed)]
MS (ESI) m/z 711.6 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.38 (s, 1H), 8.27 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46-7.34 (m, 3H), 4.43 (d, J = 5.3 Hz, 2H), 4.27 (s, 2H), 4.14 (s, 2H), 3.30 (d, J = 11.8 Hz, 2H), 2.77 (d, J = 20.8 Hz, 7H), 2.68 (s, 3H), 1.88 (s, 3H)
484[Figure (not displayed)]
MS (ESI) m/z 615.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 1.7 Hz, 1H), 8.24 (s, 1H), 7.98-7.94 (m, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.53 (s, 1H), 7.41 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.81 (s, 2H), 4.41 (t, J = 5.1 Hz, 2H), 4.25 (t, J = 5.1 Hz, 2H), 1.77 (s, 3H)
485[Figure (not displayed)]
MS (ESI) m/z 711.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 8.22 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 2.5 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.1 Hz, 2H), 4.26 (d, J = 5.0 Hz, 2H), 3.95 (s, 2H), 3.38 (d, J = 11.4 Hz, 2H), 2.92 (d, J = 11.8 Hz, 4H), 2.78 (d, J = 4.5 Hz, 3H), 2.70 (s, 3H), 1.85 (s, 3H)
486[Figure (not displayed)]
MS (ESI) m/z 711.6 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (d, J = 2.5 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.89 (s, 2H), 3.53 (s, 4H), 2.70 (s, 3H), 1.83 (s, 3H)
487[Figure (not displayed)]
MS (ESI) m/z 791.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 8.33 (d, J = 1.8 Hz, 1H), 7.96-7.93 (m, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 5.0 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.1 Hz, 2H), 2.61 (s, 4H), 1.86 (s, 3H)
489[Figure (not displayed)]
MS (ESI) m/z 741.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.21 (s, 1H), 7.97 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.48-7.41 (m, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.74 (s, 2H), 4.41 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 3.94 (s, 2H), 2.92 (d, J = 12.0 Hz, 5H), 2.78 (d, J = 4.2 Hz, 3H), 1.77 (s, 3H)
494[Figure (not displayed)]
MS (ESI) m/z 735.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.98 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.51 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 4.08- 3.82 (m, 4H), 3.38 (d, J = 6.2 Hz, 2H), 3.16- 3.02 (m, 1H), 1.79 (s, 3H)
495[Figure (not displayed)]
MS (ESI) m/z: 599.01; 1H-NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.36 (s, 1H), 8.22 (s, 1H), 8.01 (s, 1H), 7.59-7.56 (m, 1H), 7.37- 7.35 (m, 2H), 4.48-4.44 (m, 1H), 4.27-4.20 (m, 3H), 2.08 (s, 3H), 1.17 (s, 3H)
496[Figure (not displayed)]
MS (ESI) m/z 569.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.34 (d, J = 4.28 Hz, 1H), 8.23 (s, 1H), 7.44 (dd, J = 8.80, 2.40 Hz, 1H), 7.25 (d, J = 2.16 Hz, 1H), 7.21 (d, J = 8.84 Hz, 1H), 7.10 (s, 1H), 4.41-4.29 (m, 4H), 4.08 (t, J = 8.48, 1H), 2.12-2.10 (m, 4H), 2.03 (s, 3H)
501[Figure (not displayed)]
MS (ESI) m/z 684.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.28 (s, 1H), 7.99 (s, 1H), 7.61 (dd, J = 8.92, 2.6 Hz, 1H), 7.51 (d, J = 4.76 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.00 Hz, 1H), 4.42 (t, J = 5.76 Hz, 2H), 4.26 (t, J = 4.36 Hz, 2H), 3.95 (bs, 2H), 3.55 (bs, 4H), 2.56 (bs, 4H), 1.76 (s, 3H)
502[Figure (not displayed)]
MS (ESI) m/z 697.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.76, 1H), 8.23 (s, 1H), 7.98 (s, 1H), 7.61 (dd, J = 8.84, 2.56 Hz, 1H), 7.48 (d, J = 4.76 Hz, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.00 Hz, 1H), 4.42 (t, J = 3.8 Hz, 2H), 4.26 (t, J = 5.8, 2H), 3.94 (bs, 2H), 3.40 (d, J = 10.68 Hz, 2H), 2.94 (d, J = 10.68 Hz, 4H), 2.79 (d, J = 3.4 Hz, 3H), 2.50 (m, 2H), 1.77 (s, 3H)
503[Figure (not displayed)]
MS (ESI) m/z 660.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 4.68 Hz, 1H), 8.11 (s, 1H), 8.07 (s,1H), 7.63 (d, J = 8.36, 1H), 7.57 (d, J = 11.32 Hz, 1H), 7.49 (d, J = 4.72 Hz, 1H), 4.63 (bs, 2H), 4.46 (t, J = 4.64 Hz, 2H), 4.28 (t, J = 4.72 Hz, 2H), 2.89 (bs, 6H), 1.75 (s, 3H)
505[Figure (not displayed)]
MS (ESI) m/z 637.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 4.76 Hz, 1H), 8.25 (s, 1H), 8.08 (s, 1H), 7.63 (d, J = 8.32 Hz, 1H), 7.55 (d, J = 11.2 Hz, 1H), 7.50 (d, J = 4.68 Hz, 1H), 4.43 (t, J = 5.00 Hz, 2H), 4.26 (t, J = 4.44 Hz, 2H), 1.68 (s, 3H)
519[Figure (not displayed)]
MS (ESI) m/z 696.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.69 (s, 1H), 8.92 (d, J = 4.44 Hz, 1H), 8.34 (s, 1H), 8.09 (s, 1H), 7.65- 7.54 (m, 2H), 7.45 (d, J = 1.84 Hz, 1H), 7.36 (d, J = 8.84 Hz, 1H), 4.42 (t, J = 4.68 Hz, 2H), 4.24 (t, J = 5.24 Hz, 2H), 3.56 (s, 3H), 1.65 (s, 3H)
521[Figure (not displayed)]
MS (ESI) m/z 648.07 [M + 1]+. 1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 8.84 (d, J = 4.80 Hz, 1H), 8.12 (s, 1H), 8.09 (S, 1H), 7.59 (dd, J = 8.88, 2.80 1H), 7.46 (d, J = 4.76 Hz, 1H), 7.41 (d, J = 2.60 Hz,1H), 7.34 (d, J = 9.04 Hz, 1H), 4.42-4.38 (m, 2H), 4.28-4.21 (m, 2H), 3.88 (s, 3H), 1.66 (s, 3H)
522[Figure (not displayed)]
MS (ESI) m/z 718.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.16 Hz, 1H), 8.27 (s, 1H), 8.98 (s, 1H), 7.59 (d, J = 8.52 Hz, 1H), 7.50 (d, J = 4.4 Hz, 1H), 7.43 (s, 1H), 7.36 (d, J = 9.08 Hz, 1H), 4.41 (bs, 2H), 4.24 (bs, 2H), 3.94 (s, 2H), 2.61 (s, 4H), 1.92 (s, 4H), 1.76 (s, 3H)
523[Figure (not displayed)]
MS (ESI) m/z 710.21 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 8.82 (d, J = 3.2 Hz, 1H), 8.27 (s, 1H), 7.99 (s, 1H), 7.59 (d, J = 8.88 Hz, 1H), 7.50-7.42 (m, 1H), 7.43 (s, 1H) 7.35 (d, J = 8.24 Hz, 1H), 4.41 (s, 2H), 4.24 (s, 2H), 3.84 (s, 1H), 3.50-3.30 (m, 4H), 3.07 (s, 2H), 2.02 (s, 2H), 1.85- 1.70 (m, 5H)
524[Figure (not displayed)]
MS (ESI) m/z 616.13 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.27 (bs, 1H), 8.82 (s, J = 4.72 Hz, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.58 (dd, J = 8.80, 2.44 Hz, 1H ), 7.46 (d, J = 4.76 Hz, 1H), 7.40 (d, J = 2.52 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 5.52 (s, 2H), 4.40 (t, J = 4.28 Hz, 2H), 4.23 (t, J = 5.2 Hz, 2H), 1.73 (s, 3H)
525[Figure (not displayed)]
MS (ESI) m/z 692.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.23 (s, 1H), 7.97 (s, 1H), 7.65-7.26 (m, 4H), 6.16 (t, J = 56.26 Hz, 1H), 4.40 (s, 2H), 4.24 (s, 2H), 4.04 (s, 2H), 2.94 (t, J = 14.2 Hz, 2H), 2.28 (s, 3H), 1.75 (s, 3H)
526[Figure (not displayed)]
MS (ESI) m/z 668.20 [M + 1]+; 1H-NMR (400 MHz, CD3OD) δ 8.80 (d ,J = 4.84 Hz, 1H), 8.27 (s, 1H), 8.19 (s, 1H), 7.57 (dd, J = 2.96, 9.76 Hz, 1H), 7.49 (d, J = 4.84 Hz, 1H), 7.36 (d, J = 2.36 Hz, 1H), 7.31 (d, J = 8.88 Hz, 1H), 4.98 (s, 2H), 4.46 (t, J = 2.36, 2H), 4.37 (t, J = 4.6 Hz, 2H),.3.74 (s, 4H), 2.20 (s, 4H), 2.03 (s, 3H)
527[Figure (not displayed)]
MS (ESI) m/z 670.40 [M + 1]+; 1H-NMR (400 MHz CD3OD) δ 8.78 (d, J = 4.88 Hz, 1H), 8.27 (s, 1H), 8.20 (s, 1H), 7.57 (dd, J = 2.56, 8.92 Hz, 1H), 7.49 (d, J = 4.92 Hz, 1H), 7.36 (d, J = 2.48 Hz, 1H), 7.32 (d, J = 8.84 Hz, 1H), 4.98 (s, 2H), 4.46 (t, J = 4.76, 2H), 4.37 (t, J = 4.5 Hz, 2H),.3.52-3.47 (m, 4H), 2.03 (s, 3H), 1.48-1.29 (m, 6H)
528[Figure (not displayed)]
MS (ESI) m/z 682.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 + D20) δ 8.83 (d, J = 4.80 Hz, 1H), 8.21 (s, 1H), 8.06 (s, 1H), 7.61-7.57 (dd, J = 2.48, 8.80 Hz, 1H), 7.48 (d, J = 4.68 Hz, 1H), 7.44 (d, J = 2.48 Hz, 1H), 7.36 (d, J = 8.92 Hz, 1H), 4.58 (m, 2H), 4.40 (t, J = 6.36 Hz, 2H), 4.26 (t, J = 4.52 Hz, 2H)., 3.29 (m, 4H), 1.75 (m, 7H), 1.54 (m, 2H)
535[Figure (not displayed)]
MS (ESI) m/z 537.11 [M +1]+. 1H NMR (400 MHz, DMSO-d6) δ 12.77 (bs, 1H), 8.39 (s, 1H), 7.23 (s, 1H), 7.03 (d, J = 8.9 Hz), 6.92 (s, 1H), 4.51 (m, 2H), 4.38 (t, J = 4.8 Hz, 3H), 4.19-4.16 (m, 2H), 3.95 (d, J = 11.2 Hz, 1H), 3.63-3.59 (m, 1H), 3.27 (d, J = 9.6 Hz, 1H), 2.94-2.79 (m, 5H)
549[Figure (not displayed)]
MS (ESI) m/z 651.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.72 Hz, 1H), 8.22 (s, 1H), 8.07 (s, 1H), 7.61-7.23 (m, 5H), 4.41 (t, J = 4.2 Hz, 2H), 4.26 (t, J = 4.2 Hz, 2H), 1.72 (s, 3H)
553[Figure (not displayed)]
MS (ESI) m/z 636.0 [M + 1]+;; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 4.7 Hz, 1H), 8.53 (s, 1H), 8.21 (s, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.7 (d, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.54 (d, J = 4.7 Hz, 1H), 4.91 (s, 2H), 4.63 (bs, 2H), 2.87 (bs, 6H), 2.11 (s, 3H)
554[Figure (not displayed)]
MS (ESI) m/z 613.04 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.55 (s, 1H), 8.22 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.7 (d, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 4.7 Hz, 1H), 4.88 (s, 2H), 2.07 (s, 3H)
555[Figure (not displayed)]
MS (ESI) m/z 633. [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 4.88, 1H), 8.089 (s, 1H), 7.615 (dd, J = 8.92, 8.96, 1H), 7.519 (d, J = 4.88 Hz, 1H), 7.414 (d, J = 2.6, 1H), 7.37 (d, J = 8.96 Hz, 1H), 4.43 (bs, 2H), 4.29 (bs, 2H), 2.41 (s, 3H), 1.89 (s, 3H)
556[Figure (not displayed)]
MS (ESI) m/z 656.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.76, 1H), 8.088 (s,1H), 7.618 (dd, J = 8.84, 8.72, 1H), 7.517 (d, J = 4.84 Hz, 1H), 7.44 (d, J = 2.16, 1H), 7.36 (d, J = 8.88 Hz, 1H), 4.602 (bs, 2H), 4.419 (bs, 2H), 4.28 (bs, 2H), 2.84 (bs, 6H), 2.34 (s, 3H), 1.83 (s, 3H)
558[Figure (not displayed)]
MS (ESI) m/z 633.10 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.24 (s ,1H), 8.03 (s, 1H), 7.61-7.58 (dd, J = 2.52,J = 8.84 Hz, 1H), 7.44 (s, 1H),-7.41 (d, J = 2.52, 1H),7.37 (d, J = 8.92, 1H), 4.42 (t, J = 5.46 Hz, 2H), 4.27 (t, J = 4.32 Hz, 2H), 2.71 (s, 3H),1.79 (s, 3H)
559[Figure (not displayed)]
MS (ESI) m/z 656.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.48 (s, 1H), 8.06 (bs, 1H), 8.03 (s, 1H), 7.62 (dd, J = 8.92 Hz, 2.52 Hz, 1 H), 7.45-7.34 (m, 2 H), 7.36 (d, J = 8.32 Hz, 1H), 4.75 (s, 2 H), 4.44 (t, J = 3.6 Hz, 2H), 4.29 (t, J = 5.6 Hz, 2 H), 2.99 (s, 6H), 2.72 (s, 3H), 1.82 (s, 3 H)
560[Figure (not displayed)]
MS (ESI) m/z: 593 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 8.59 (s, 1H), 8.42 (s, 1H), 8.12 (s, 1H), 7.75 (d, J = 8.24 Hz, 1H), 7.68-7.64 (m, 2H), 7.46 (s, 1H), 4.87 (s, 2H), 2.59 (s, 3H), 2.14 (s, 3H)
561[Figure (not displayed)]
MS (ESI) m/z 627.06 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) 13.23 (bs, 1H), 8.54 (s, 1H), 8.20 (s, 1H), 7.75 (d, J = 8.32 Hz, 1H), 7.69 (dd, J = 8.24, 1.96 Hz, 1H), 7.64 (s, 1H), 7.47 (s, 1H), 4.87 (s, 2H). 2.64 (s, 3H), 2.14 (s 3H)
562[Figure (not displayed)]
MS (ESI) m/z 650.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.34 (bs, 1H), 8.73 (d, J = 4.7 Hz, 1H), 8.66 (s, 1H), 8.13 (d, J = 9.7 Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.68 (m, 1H), 7.53 (d, J = 4.7 Hz, 1H), 7.37 (t, J = 53.7 Hz, 1H), 4.88 (s, 2H), 2.22 (s, 3H)
563[Figure (not displayed)]
MS (ESI) m/z 635.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (bs, 1H), 8.37 (s, 1H), 8.28 (s, 1H), 8.00 (s, 1H), 7.67 (s, 1H), 7.60 (dd, J = 1.68, 8.56 Hz, 1H), 7.45 (bs, 1H), 7.35 (d, J = 8.88 Hz, 1H), 7.18 (t, J = 54.84 Hz, 1H), 4.39-4.35 (m, 2H), 4.23-4.20 (m, 2H), 1.67 (s, 3H)
564[Figure (not displayed)]
MS (ESI) m/z 655.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 9.45 (s, 1H), 8.18 (s, 1H), 7.50 (dd, J = 2.52 Hz, J = 9.12 Hz, 2H), 7.28-7.25 (m, 2H), 7.15 (d, J = 7.28 Hz, 1H), 4.75 (s, 2H), 4.36 (bs, 2H), 4.24 (bs, 2H), 2.98 (s, 6H), 2.68 (s, 3H), 1.72 (s, 3H)
565[Figure (not displayed)]
MS (ESI) m/z 676.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (bs, 1H), 8.38 (s, 1H), 8.35 (s, 1H), 7.60 (dd, J = 8.80, 2.40 Hz, 1H), 7.47 (s, 1H), 7.42 (d, J = 2.48 Hz, 1H), 7.35 (d, J = 8.16 Hz, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4. 24 (t, J = 4.72 Hz, 2H), 3.56 (s, 3H), 2.68 (s, 3H), 1.78 (s, 3H)
568[Figure (not displayed)]
MS (ESI) m/z 733.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.32 (s, 1H), 7.97 (s, 1H), 7.61-7.59 (m, 1H), 7.48 (s, 1H), 7.43 (s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.41 (s, 2H), 4.23 (bs, 2H), 3.77 (bs, 2H), 3.55 (s, 3H), 2.69 (s, 3H), 2.22 (s, 6H), 1.75 (s, 3H)
569[Figure (not displayed)]
MS (ESI) m/z 662.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.70 (s, 1H), 8.89 (d, J = 4.76 Hz, 1H), 8.39 (s, 2H), 8.02 (s, 1H), 7.63- 7.60 (dd, J = 2.56, 2.44 Hz 1H), 7.56 (d, J = 4.72 Hz, 1H), 7.46 (d, J = 2.44 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 4.4 Hz, 2H), 4.24 (t, J = 3.86 Hz, 2H), 3.56 (s, 3H), 1.73 (s, 3H)
571[Figure (not displayed)]
MS (ESI) m/z 617.11 [M + 1]+; 1H NMR (400 MHz, MeOD) δ 8.31 (s, 1H), 8.16 (s, 1H), 8.00 (s, 1H), 7.56 (s, 1H),7.51 (d, J = 8.08 Hz, 1H), 7.34 (d, J = 10.84 Hz, 1H), 4.50 (t, J = 4.80 Hz, 2H), 4.38 (t, J = 5.20 Hz, 2H), 2.96 (s, 3H), 2.03 (s, 3H)
589[Figure (not displayed)]
MS (ESI) m/z 617.11 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.36 (d, J = 5.64 Hz, 1H), 7.60 (dd, J = 8.88, 2.64 Hz, 1H), 7.43-7.39 (m, 2H), 7.36 (d, J = 9.00 Hz, 1H), 4.42 (t, J = 4.52 Hz, 2H), 4.28 (t, J = 4.76 Hz, 2H), 2.69 (s, 3H), 1.94 (s, 3H)
590[Figure (not displayed)]
MS (ESI) m/z 615.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.95-7.93 (m, 3H), 7.57 (dd, J = 2.56, 8.92 Hz, 1H), 7.39 (d, J = 2.52 Hz, 1H), 7.33 (d, J = 9.04 Hz, 1H), 4.39 (t, J = 4.48 Hz, 2H), 4.30 (t, J = 4.36 Hz, 2H), 3.69 (s, 3H), 2.10 (s, 3H)
591[Figure (not displayed)]
MS (ESI) m/z 612.91 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 14.09 (bs, 1H), 68.77 (d, J = 4.56 Hz, 1H), 8.37 (s, 1H), 7.97 (s, 1H), 7.59 (d, J = 8.48 Hz, 1H), 7.50 (d, J = 4.56 Hz, 1H), 7.42 (bs, 1H), 7.35 (d, J = 8.84 Hz, 1H), 4.42 (t, J = 4.32 Hz, 2H), 4.26 (t, J = 3.20 Hz, 2H), 2.85-2.79 (m, 2H), 1.85 (s, 3H), 0.97 (t, J = 7.24 Hz, 3H)
595[Figure (not displayed)]
MS (ESI) m/z 629.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37-8.28 (m, 2H), 7.61 (s, 1H), 7.48-7.43 (m, 1H), 7.31-7.26 (m, 2H), 7.05 (bs, 1H), 4.33 (bs, 2H), 4.24 (bs, 2H), 3.81 (s, 2H), 3.01 (s, 2H), 1.80 (s, 3H)
605[Figure (not displayed)]
MS (ESI) m/z 615.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.16 (s, 1H), 7.52 (d, J = 7.44, 1H), 7.36 (s, 1H), 7.29 (d, J = 9.04 Hz, 1H), 6.54 (s, 1H), 6.30 (s, 1H), 4.88 (s, 2H), 4.38 (s, 2H), 4.31 (s, 2H), 2.32 (s, 3H)
610[Figure (not displayed)]
MS (ESI) m/z 670.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.93 (s, 1H), 7.59 (dd, J = 8.68, 2.16 Hz, 1H), 7.41-7.34 (m, 3H), 4.40 (t, J = 4.76 Hz, 2H), 4.24 (t, J = 4.68 Hz, 2H), 3.20 (d, J = 7.48 Hz, 2H), 2.69 (s, 3H), 2.57 (d, J = 10.48 Hz, 2H), 2.28 (s, 6H), 1.83 (s, 3H)
614[Figure (not displayed)]
MS (ESI) m/z 617.06 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.14 (bs, 2H), 7.74 (t, J = 8.56 Hz, 1H), 7.29 (bs, 1H), 7.20 (d, J = 9.08 Hz, 1H), 4.41 (bs, 1H), 4.36 (bs, 1H), 4.23 (s, 2H), 2.66 (s, 3H), 1.70 (s, 3H)
615[Figure (not displayed)]
MS (ESI) m/z 691.19 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 4.72 Hz, 1H), 8.48 (s, 1H), 8.06 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 7.1 Hz, 1H), 7.57 (s, 1H), 7.47 (d, J = 4.64, 1H), 4.78 (s, 2H), 3.95 (s, 2H), 3.37 (d, J = 12.5 Hz, 2H), 2.97 (d, J = 10.68 Hz, 4H), 2.75 (s, 3H), 2.58-2.56 (m, 2H), 2.1 (s, 3H)
616[Figure (not displayed)]
MS (ESI) m/z 705.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.43 (s, 1H), 8.54 (s, 1H), 8.11 (s, 1H), 7.75 (d, J = 8.32 Hz, 1H), 7.69 (dd, J = 8.36, 6.2 Hz, 1H), 7.65 (d, J = 1.96 Hz, 1H), 7.47 (s, 1H), 4.87 (s, 2H), 3.97 (s, 2H), 2.95 (d, J = 10.08 Hz, 4H), 2.80 (s, 3H), 2.66 (s, 3H), 2.62 (s, 4H), 2.17 (s, 3H)
617[Figure (not displayed)]
MS (ESI) m/z 678.16 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 4.76 Hz, 1H), 8.6 (s, 1H), 8.1 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 4.76 Hz, 1H), 4.88 (s, 2H), 3.97 (s, 2H), 3.56 (s, 4H), 2.58 (s, 4H), 2.13 (s, 3H)
629[Figure (not displayed)]
MS (ESI) m/z 676.18 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 5.56 Hz, 2H), 8.25 (s, 1H), 8.09 (s, 1H), 7.59 (dd, J = 7.56 Hz, 2.64 Hz, 1H), 7.53 (d, J = 4.88 Hz, 2H), 7.42-7.40 (m, 2H), 7.36 (d, J = 8.92 Hz, 1H), 4.41 (t, J = 4.76 Hz ,2H), 4.28 (t, J = 4.36 Hz, 2H), 2.72 (s, 3H), 1.86 (s, 3H)
630[Figure (not displayed)]
MS (ESI) m/z 676.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 3.7, 1H), 8.69 (s, 1H), 8.31 (s, 1H), 8.05 (s,1H), 7.99 (d, J = 7.8 Hz, 1H), 7.66- 7.58 (m, 2H), 7.45 (s, 1H), 7.424 (d, J = 2.56 Hz, 1H), 7.36 (d, J = 8.9, 1H), 4.42 (t, J = 9.2 Hz, 2H), 4.28 (t, J = 9.6 Hz, 2H), 2.73 (s, 3H), 1.87 (s, 3H)
631[Figure (not displayed)]
MS (ESI) m/z 676.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 4.7 Hz, 1H), 8.37 (s, 1H), 8.07 (s, 1H), 8.03 (t, J = 7.8 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.61-7.52 (m, 2H), 7.43 (s, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.40 (s, 2H), 4.26 (s, 2H), 2.72 (s, 3H), 1.83 (s, 3H)
632[Figure (not displayed)]
MS (ESI) m/z 665.30 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6), 13.51 (bs, 1H), 8.26 (s ,1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.60 (dd, J = 2.36, 8.88 Hz, 1H), 7.52 (s, 1H), 7.44 (s, 1H),7.42 (d, J = 2.52 Hz, 1H), 7.37 (d, J = 8.88 Hz, 1H), 7.19 (s, 1H), 4.42 (t, J = 5.28 Hz, 2H), 4.28 (t, J = 4.24 Hz, 2H), 2.73 (s, 3H), 1.87 (s, 3H)
633[Figure (not displayed)]
MS (ESI) m/z 665.23 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) 8.35 (s ,1H), 8.19 (d, J = 2.08 Hz,1H), 8.11 (s, 1H), 7.87 (d, J = 1.52 Hz, 1H), 7.61-7.58 (dd, J = 2.64, 8.88 Hz, 1H), 7.44- 7.42 (m, 2H), 7.37 (d, J = 8.88 Hz, 1H), 6.63 (t, J = 2.24 Hz, 1H), 4.41 (t, J = 4.52 Hz, 2H), 4.28 (t, J = 4.12 Hz, 2H), 2.72 (s, 3H), 1.84 (s, 3H)
634[Figure (not displayed)]
MS (ESI) m/z 697.13 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 13.51 (bs, 1H), 9.75 (bs, 1H), 8.23 (s, 1H), 7.92 (s, 1H), 7.61-7.58 (t, J = 6.5 Hz, 1H), 7.42-7.41 (t, J = 6.5 Hz, 2H), 7.37 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 6.2 Hz, 2H), 4.24 (t, J = 6.1 Hz, 2H), 3.83 (m, 2H), 3.49 (m, 2H), 3.24 (m, 2H), 3.03 (m, 2H), 2.28 (s, 3H), 2.71 (s, 3H), 1.82 (s, 3H)
636[Figure (not displayed)]
MS (ESI) m/z 642.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.87 (bs, 1H), 9.92 (s, 1H), 8.39 (s, 1H), 8.29 (s, 1H), 8.03 (s, 1H), 7.62 (dd, J = 2.40, 8.8 Hz, 1H), 7.57 (s, 1H), 7.42 (d, J = 3.28 Hz, 1H), 7.37 (d, J = 8.92 Hz, 1H), 4.63 (bs, 2H), 4.43 (t, J = 4.84 Hz, 2H), 4.26 (t, J = 4.64 Hz, 2H), 2.96 (s, 6H), 1.76 (s, 3H
637[Figure (not displayed)]
MS (ESI) m/z 725.09 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.18 (s,1H), 7.94 (s, 1H), 7.61-7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.46 (s, 1H), 7.44 (d, J = 2.48 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.41 (t, J = 5.2 Hz, 2H), 4.24 (t, J = 5.2 Hz, 2H), 3.94 (s, 2H), 3.40-3.37 (m, 2H), 3.04-2.98 (m, 2H), 2.92 (m, 4H), 2.78 (d, J = 3.52 Hz, 3H), 2.54 (m, 2H), 1.80 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H)
638[Figure (not displayed)]
MS (ESI) m/z 727.07 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 12.7 (bs, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.59-7.56 (dd, J = 2.8, 9.2 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 6.90 (s, 1H), 4.41 (t, J = 6.4 Hz, 2H), 4.28 (t, J = 5.6 Hz, 2H), 4.07 (s, 3H), 3.94 (s, 2H), 3.39 (d, J = 11.2 Hz, 2H), 2.91 (d, J = 11.2 Hz, 4H), 2.78 (d, J = 3.2 Hz, 2H), 2.56 (d, J = 7.6 Hz, 2H), 1.88 (s, 3H)
640[Figure (not displayed)]
MS (ESI) m/z 751.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 4.9 Hz, 1H), 8.32 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.53 (d, J = 4.9 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 4.9 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 3.31 (q, J = 10.1 Hz, 2H), 3.07-2.58 (m, 6H), 1.75 (s, 3H). Note: piperazine protons were very broad and could not be properly integrated
641[Figure (not displayed)]
MS (ESI) m/z 642.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 4.92 Hz, 1H), 8.15 (s, 1H), 7.86 (s, 1H), 7.61 (dd, J = 8.6, 2.4 Hz, 1H), 7.47 (m, 2H), 7.37 (d, J = 9 Hz, 1H), 4.67 (s, 2H), 4.41 (t, J = 5.28 Hz, 2H), 4.25 (t, J = 4.28 Hz, 2H), 2.88 (s, 6H), 2.53 (s, 3H)
642[Figure (not displayed)]
MS (ESI) m/z 726.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.44 (bs, 1H), 8.27 (s, 1H), 7.95 (s, 1H), 7.59 (dd, J = 8.8, 2.5 Hz, 1H), 7.42-7.41 (m, 2H), 7.35 (d, J = 8.9 Hz, 1H), 4.4 (t, J = 5.9 Hz, 2H), 4.24 (t, J = 5.6 Hz, 2H), 3.83 (s, 2H), 3.47-3.43 (m, 2H), 2.68 (s, 3H), 2.62 (d, J = 10.5 Hz, 2H), 1.89 (d, J = 6.2 Hz, 2H), 1.86 (s, 3H), 1.01 (d, J = 6.2 Hz, 6H)
643[Figure (not displayed)]
MS (ESI) m/z 705.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 4.84 Hz, 1H), 8.05 (s, 1H), 7.75 (d, J = 8.20 Hz, 1H), 7.69 (d, J = 8.48 Hz, 1H), 7.65 (s, 1H), 7.57 (d, J = 4.76 Hz, 1H), 4.88 (s, 2H), 3.86 (s, 2H), 2.50- 2.32 (m, 8H, merged with moisture peak in DMSO), 2.17 (s, 3H), 2.10 (s, 3H), 1.23 (s, 3H)
644[Figure (not displayed)]
MS (ESI) m/z 743.07 [M + 1]+.;; 1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.62-7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.59 (s, 1H), 7.43 (d, J = 2.4 Hz, 1H ), 7.37 (d, J = 8.8 Hz, 1H), 4.99 (t, J = 6.0 Hz, 1H), 4.87 (t, J = 6.0 Hz, 1H), 4.42 (t, J = 6.4 Hz, 2H), 4.26 (t, J = 6.8 Hz, 2H), 3.94 (s, 2H), 3.45 (t, J = 6.0 Hz, 2H), 2.93 (m, 4H), 2.78 (s, 3H), 2.50 (m, 2H), 1.76 (s, 3H)
645[Figure (not displayed)]
MS (ESI) m/z 729.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.04 (bs, 1H), 9.40 (s, 1H), 8.26 (s, 1H), 7.99 (s, 1H), 7.60 (dd, J = 2.28, 8.72 Hz, 1H), 7.53 (bs, 1H), 7.44 (d, J = 2.32 Hz, 1H), 7.36 (d, J = 8.92 Hz, 1H), 5.76-5.65 (d, J = 46.8 Hz, 2H), 4.41 (t, J = 5.16 Hz, 2H), 4.25 (t, J = 5.72 Hz, 2H), 3.94 (s, 2H), 3.40-3.37 (m, 2H), 2.93-2.90 (m, 4H), 2.79 (d, J = 3.32 Hz, 3H), 2.56-2.54 (m, 2H), 1.77 (s, 3H)
649[Figure (not displayed)]
MS (ESI) m/z 697.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.52 (bs, 2H), 8.22 (s, 1H), 7.59 (s, 1H), 7.61 (dd, J = 2.76, 8.64 Hz, 1H), 7.42 (s, 2H), 7.37 (d, J = 9.0, 1H), 4.42 (t, J = 4.44 Hz, 2H), 4.26 (t, J = 4.96 Hz, 2H), 3.93 (s, 2H), 3.07 (s, 4H), 2.70 (m, 6H ), 1.84 (s , 3H)
652[Figure (not displayed)]
MS (ESI) m/z 667.97 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.29 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 2.56 Hz, 8.8 Hz, 1H), 7.41 (s, 2H), 7.37 (d, J = 9.0 Hz, 1H ), 4.39 (m, 2H), 4.26 (m, 3H), 3.96 (bs, 2H), 3.55 (bs, 2H), 2.70 (s, 3H), 2.35 (s, 3H), 1.85 (s, 3H)
655[Figure (not displayed)]
MS (ESI) m/z 715.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.25 (s, 1H), 7.96 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.89 (dt, J = 47.3, 4.5 Hz, 2H), 4.41 (t, J = 5.0 Hz, 2H), 4.25 (t, J = 5.0 Hz, 2H), 4.03-3.88 (m, 2H), 3.74-3.09 (m, 8H), 1.77 (s, 3H)
660[Figure (not displayed)]
LCMS (ESI) m/z 553.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 2.1 Hz, 1H), 8.71 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 1.8, 0.7 Hz, 1H), 8.23 (t, J = 2.1 Hz, 1H), 7.80 (dd, J = 1.7, 0.8 Hz, 1H), 7.50-7.39 (m, 2H), 7.26 (d, J = 8.9 Hz, 1H), 4.43-4.31 (m, 4H), 2.11 (s, 3H)
661[Figure (not displayed)]
LCMS (ESI) m/z 569.1 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.3 Hz, 1H), 8.37-8.31 (m, 1H), 8.07 (dt, J = 1.7, 0.8 Hz, 1H), 7.98 (s, 1H), 7.64-7.47 (m, 3H), 7.29 (d, J = 9.0 Hz, 1H), 7.22 (d, J = 4.2 Hz, 1H), 4.35 (t, J = 5.0 Hz, 2H), 4.21 (t, J = 4.9 Hz, 2H), 1.79 (s, 3H)
662[Figure (not displayed)]
LCMS (ESI) m/z 553.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.71 (dd, J = 5.0, 0.8 Hz, 1H), 8.34- 8.28 (m, 1H), 8.05 (dd, J = 1.7, 0.8 Hz, 1H), 7.88 (dd, J = 1.8, 0.8 Hz, 1H), 7.57 (dd, J = 5.0, 1.7 Hz, 1H), 7.52-7.40 (m, 2H), 7.26 (d, J = 8.9 Hz, 1H), 4.44-4.31 (m, 4H), 2.96 (s, 3H), 2.13 (s, 3H).5 (t, J = 4.7 Hz, 2H), 1.69 (s, 3H)
663[Figure (not displayed)]
LCMS (ESI) m/z 557.0 [M + 1]+1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 4.7 Hz, 1H), 8.32 (s, 1H), 8.11 (s, 1H), 7.51 (dd, J = 8.9, 2.7 Hz, 1H), 7.33 (d, J = 2.6 Hz, 1H), 7.28 (d, J = 9.0 Hz, 1H), 7.22 (d, J = 4.4 Hz, 1H), 6.32 (d, J = 1.6 Hz, 1H), 4.34 (s, 2H), 4.23 (s, 2H), 1.81 (s, 3H)
664[Figure (not displayed)]
LCMS (ESI) m/z 615.0 [M + 1]+1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 1.9 Hz, 1H), 8.35 (d, J = 1.9 Hz, 1H), 8.32-8.28 (m, 1H), 8.01 (dd, J = 1.7, 0.8 Hz, 1H), 7.49-7.40 (m, 2H), 7.25 (dd, J = 8.6, 0.6 Hz, 1H), 4.36 (dd, J = 11.4, 4.4 Hz, 4H), 3.85 (s, 3H), 2.19 (s, 3H)
666[Figure (not displayed)]
LCMS (ESI) m/z 653.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.88 (d, J = 4.7 Hz, 1H), 8.38-8.32 (m, 1H), 8.17-8.05 (m, 1H), 7.61- 7.51 (m, 2H), 7.42 (d, J = 2.6 Hz, 1H), 7.32
667[Figure (not displayed)]
LCMS (ESI) m/z 627.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 5.0 Hz, 1H), 8.35 (dd, J = 1.7, 0.6 Hz, 1H), 7.97 (dt, J = 1.7, 0.8 Hz, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 5.0 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 4.37 (t, J = 5.0 Hz, 1H), 4.23 (t, J = 5.1 Hz, 1H), 3.85 (q, J = 6.8 Hz, OH), 1.83 (s, 2H), 0.99 (d, J = 6.8 Hz, 3H)
668[Figure (not displayed)]
LCMS (ESI) m/z 613.3 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 1.7 Hz, 1H), 7.93 (dt, J = 1.7, 0.8 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.42-7.29 (m, 2H), 4.39 (t, J = 5.0 Hz, 1H), 4.24 (t, J = 5.0 Hz, 1H), 2.66 (s, 2H), 2.35 (s, 2H), 1.92 (s, 2H)
670[Figure (not displayed)]
LCMS (ESI) m/z 670.2 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.43- 7.36 (m, 2H), 7.32 (d, J = 9.0 Hz, 1H), 4.38 (t, J = 4.9 Hz, 2H), 2.67 (s, 4H), 2.32 (s, 3H), 1.87 (s, 3H)
672[Figure (not displayed)]
LCMS (ESI) m/z 625.9 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 1.7 Hz, 1H), 8.17 (s, 1H), 7.92 (d, J = 1.7 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.44-7.38 (m, 2H), 7.32 (d, J = 9.0 Hz, 1H), 4.36 (t, J = 5.1 Hz, 2H), 4.23 t, J = 5.1 Hz, 2H), 1.78 (s, 3H)
675[Figure (not displayed)]
LCMS (ESI) m/z 690.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.03 (s, 1H), 7.87 (t, J = 7.8 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.46-7.36 (m, 5H), 7.33 (d, J = 9.0 Hz, 1H), 4.37 (s, 2H), 4.24 (s, 2H), 2.69 (s, 3H), 2.50 (s, 4H), 1.80 (s, 3H)
684[Figure (not displayed)]
LCMS (ESI) m/z 708.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.06 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.56 (dd, J = 9.3, 2.3 Hz, 1H), 7.43 (dd, J = 6.7, 4.0 Hz, 3H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (bs, 2H), 4.28 (bs, 2H), 2.73 (s, 3H), 2.56 (s, 3H), 1.85 (s, 3H)
686[Figure (not displayed)]
LCMS (ESI) m/z 704.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 5.4 Hz, 1H), 8.27 (s, 1H), 8.08 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.50-7.38 (m, 3H), 7.33 (d, J = 9.0 Hz, 1H), 4.39 (m, 2H), 4.25 (m 2H), 2.70 (s, 3H), 2.61 (s, 3H), 2.00 (s, 3H), 1.81 (s, 3H)
687[Figure (not displayed)]
LCMS (ESI) m/z 690.2 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.85 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.86 (t, J = 12.5 Hz, 4H), 4.39 (t, J = 5.0 Hz, 2H), 4.22 (t, J = 5.0 Hz, 2H), 2.72 (s, 3H), 1.79 (s, 3H)
705[Figure (not displayed)]
MS (ESI) m/z 639.0 [M + 1]+; 1H-NMR (400 MHz, d6- DMSO) δ/ppm = 9.81-9.70 (b, 1H), 8.63 (d, J = 4.7 Hz, 1H), 8.09 (s, 1H), 7.72 (d, J = 5.4 Hz, 1H), 7.56 (dd, J = 8.9, 2.6 Hz, 1H), 7.38 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 5.4 Hz, 1H), 7.33 (d, J = 8.9 Hz, 1H), 7.22 (d, J = 4.7 Hz, 1H), 4.38 (t, J = 4.9 Hz, 2H), 4.27 (t, J = 4.9 Hz, 2H), 3.92-3.82 (m, 2H), 3.59- 3.50 (m, 2H), 3.30-3.20 (m, 2H), 3.14-3.01 (m, 2H), 2.91 (bs, 3H), 1.90 (s, 3H)
706[Figure (not displayed)]
MS (ESI) m/z 650.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.71-8.64 (m, 2H), 8.29 (d, J = 0.6 Hz, 1H), 7.90 (dd, J = 9.2, 3.0 Hz, 1H), 7.78 (d, J = 5.6 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 5.5 Hz, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.33 (d, J = 8.9 Hz, 1H), 7.26 (d, J = 4.7 Hz, 1H), 4.43-4.35 (m, 2H), 4.34-4.15 (m, 1H), 2.19 (d, J = 1.0 Hz, 3H), 1.88 (s, 3H)
708[Figure (not displayed)]
MS (ESI) m/z 682.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.90 (s, 1H), 7.63-7.56 (m, 1H), 7.46-7.38 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.49-4.32 (m, 2H), 4.31-4.18 (m, 2H), 3.70-3.66 (m, 1H), 3.26-3.22 (m, 2H), 2.69 (s, 3H), 2.32-2.22 (m, 2H), 2.22-2.09 (m, 2H), 2.07 (s, 3H), 1.80 (s, 3H)
709[Figure (not displayed)]
MS (ESI) m/z 684.07 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) 8.23 (s, 1H), 7.94 (s, 1H), 7.60 (dd, J = 8.80, 2.40 Hz, 1H), 7.44-7.38 (m, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.76 Hz, 2H), 4.25 (t, J = 4.24 Hz, 2H), 3.05-3.01 (m, 4H), 2.69 (s, 3H), 2.50-2.30 (m, 6H), 1.91- 1.78 (m, 5H)
711[Figure (not displayed)]
MS (ESI) m/z 670.05 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.89 (s, 1H), 7.59 (dd, J = 8.80, 2.40, 1H), 7.45-7.40 (m, 2H), 7.35 (d, J = 8.84 Hz, 1H), 4.39 (t, J = 5.40 Hz, 2H),), 4.30-4.22 (m, 2H) 3.72-3.67 (m, 1H), 2.70 (s, 3H), 2.16 (s, 6H), 1.80 (s, 3H), 1.55 (d, J = 6.68 Hz, 3H)
713[Figure (not displayed)]
MS (ESI) m/z 710.17 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6-FD20) δ 9.18 (bs, 1H), 8.20 (s, 1H), 7.97 (s, 1H), 7.61-7.58 (dd, J = 2.4, 8.8 Hz, 1H), 7.43 (s, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.42 (t, J = 5.6 Hz, 2H), 4.26 (t, J = 3.6 Hz, 2H), 3.43 (bs, 3H), 3.06 (d, J = 6.8 Hz, 2H), 2.92-2.86 (m, 2H), 2.73-2.70 (m, 3H), 2.02 (bs, 1H), 1.83-1.78 (m, 5H), 1.63-1.54 (m, 2H)
714[Figure (not displayed)]
MS (ESI) m/z 696.11 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.50 (bs, 1H), 8.19-8.15 (m, 2H), 7.97 (s, 1H), 7.61-7.58 (dd, J = 2.8, 9.2 Hz, 1H), 7.43- 7.42 (m, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.42 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.4 Hz, 2H), 3.29 (d, J = 11.2 Hz, 2H), 3.06 (d, J = 11.2 Hz, 2H), 2.83-2.78 (m, 2H), 2.70 (s, 3H), 2.11-2.01 (m, 1H), 1.82 (s, 3H), 1.75 (d, J = 12.4 Hz, 2H), 1.59-1.50 (m, 2H)
717[Figure (not displayed)]
MS (ESI) m/z 621.98 [M + 1+9-; 1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 4.76 Hz, 1H), 8.65 (s, 1H), 8.30 (bs, 2H), 7.75 (d, J = 8.32, 1H), 7.69 (m, 2H), 7.54 (d, J = 4.72 Hz, 1H), 4.85 (s, 2H), 4.48 (s, 2H), 2.77 (s, 6H)
719[Figure (not displayed)]
MS (ESI) m/z 710.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 8.10 (s, 1H), 7.65 (s, 1H), 7.49 (dd, J = 8.76, 2.48 Hz, 1H), 7.28-7.24 (m, 3H), 7.13 (d, J = 7.32 Hz, 1H), 4.34 (t, J = 5.16 Hz, 2H), 4.22 (t, J = 5.12 Hz, 2H), 3.93 (s, 2H), 3.37 (d, J = 11.32, 2H,), 3.33- 3.29 (m, 2H, merged with moisture peak in DMSO), 2.90-2.88 (m, 4H), 2.78 (s, 3H), 2.67 (s, 3H), 1.72 (s, 3H)
735[Figure (not displayed)]
MS (ESI) m/z 690.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 3.72 Hz, 1H), 8.29 (s, 1H), 8.09 (s, 1H), 7.86 (d, J = 7.76 Hz, 1H), 7.60 (dd, J = 2.52, 8.84 Hz, 1H), 7.50 (d, J = 4.96 Hz, 1H), 7.48 (s, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.38 (d, J = 8.92 Hz, 1H), 4.43 (t, J = 6.12 Hz, 2H), 4.27 (t, J = 5.32, 2H), 2.73 (s, 3H), 2.24 (s, 3H), 1.84 (s, 3H)
736[Figure (not displayed)]
MS (ESI) m/z 690.04 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 4.0 Hz, 1H), 8.56 (s, 1H), 8.29 (s, 1H), 8.09 (s, 1H), 7.60 (dd, J = 8.8, 2.5 Hz, 1H), 7.56 (d, J = 5 Hz, 1H), 7.46 (s, 1H), 7.45 (d, J = 2.5 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.43 (bs, 2H), 4.28- 4.26 (m, 2H), 2.73 (s, 3H), 2.11 (s, 3H), 1.84 (s, 3H)
738[Figure (not displayed)]
MS (ESI) m/z 753.46 [M + 1]+.; 1H-NMR (400 MHz, CD3OD) δ 13.50 (bs, 1H), 8.94 (t, J = 8.44 Hz, 1H), 8.21 (s, 1H), 7.96 (s, 1H), 7.57 (dd, J = 2.25, 8.88 Hz, 1H),7.42 (s, 1H), 7.36 (d, J = 8.80 Hz, 1H), 4.41 (t, J = 4.32 Hz, 2H), 4.25 (t, J = 3.24 Hz, 2H), 3.96 (s, 2H),.3.50 (d, J = 10.48 Hz, 2H), 2.95 (d, J = 11.64 Hz, 2H), 2.82 (d, J = 10.52 Hz, 2H), 2.70 (s, 3H), 2.65 (d, J = 11.68 Hz, 2H), 1.85 (s, 3H), 1.30 (s, 9H)
739[Figure (not displayed)]
MS (ESI) m/z 761.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 2.44, 8.88 Hz, 1H), 7.43 (s, 1H), 7.42 (s, 1H), 7.36 (d, J = 8.96 Hz, 1H), 6.58-6.31 (m, 1H), 4.41 (t, J = 4.56 Hz, 2H), 4.25 (t, J = 4.64 Hz, 2H), 3.95 (bs, 2H), 3.60-3.45 (m, 2H), 3.32-3.11 (m, 4H), 2.77-2.72 (m, 4H), 2.70 (s, 3H), 1.83 (s, 3H)
740[Figure (not displayed)]
MS (ESI) m/z 737.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.61 (bs, 1H), 9.01 (bs, 1H), 8.23 (s, 1H), 7.96 (s, 1H), 7.59 (dd, J = 8.88, 2.56 Hz, 1H), 7.42 (s, 2H), 7.37 (d, J = 8.96 Hz, 1H), 4.41 (t, J = 4.16 Hz, 2H), 4.25 (t, J = 4.96 Hz, 2H), 3.93 (s, 2H), 3.43 (s, 2H), 3.32-3.29 (m, 2H), 2.98-2.88 (m, 2H), 2.72 (d, J = 3.60, 3H), 2.69 (s, 3H), 2.18-2.16 (m, 2H), 1.91 (d, J = 8.2 Hz, 2H), 1.84 (s, 3H)
747[Figure (not displayed)]
MS (ESI) m/z 690.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 1H), 8.30 (d, J = 10.6 Hz, 1H), 8.07 (t, J = 9.7 Hz, 2H), 7.66 (bs, 1H), 7.57 (s, 2H), 7.44 (bs, 2H), 7.36-7.29 (m, 1H), 4.39 (bs, 2H), 4.26 (bs, 2H), 3.02 (bs, 2H), 1.77 (d, J = 11.0 Hz, 3H), 1.35 (s, 3H)
751[Figure (not displayed)]
MS (ESI) m/z 693.99 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.71 (d, J = 4.6 Hz, 1H), 8.33 (s, 1H), 8.13 (s, 1H), 7.72 (t, J = 10.4 Hz, 1H), 7.60 (dd, J = 8.84, 2.28 Hz, 1H), 7.45-7.35 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.44-4.24 (m, 4H), 2.72 (s, 3H), 1.87 (s, 3H)
753[Figure (not displayed)]
MS (ESI) m/z 629.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 16.55 (s, 1H), 8.00-7.83 (m, 3H), 7.60-7.52 (m, 1H), 7.40-7.28 (m, 2H), 4.49-4.23 (m, 4H), 3.70 (s, 3H), 2.69 (s, 3H), 2.16 (s, 3H)
754[Figure (not displayed)]
MS (ESI) m/z 622.96 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 16.04 (s, 1H), 8.18 (s, 1H), 8.02 (s, 1H), 8.01 (s, 1H), 7.71 (d, J = 8.36 Hz, 1H), 7.65 (dd, J = 8.36,1.88 Hz, 1H), 7.58 (d, J = 1.72 Hz, 1H), 4.90 (s, 2H) 3.64 (s, 3H), 2.73 (s, 3H), 2.36 (s, 3H)
774[Figure (not displayed)]
MS (ESI) m/z 703.98 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.32 (s, 1H), 8.05 (s, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.60 (dd, J = 2.56, 8.88 Hz, 1H), 7.54 (d, J = 8.04 Hz, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.60 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H) 4.42 (t, J = 4.64 Hz, 2H), 4.27 (t, J = 4.20 Hz, 2H), 2.90 (q, J = 7.52 Hz, 2H), 2.73 (s, 3H), 1.87 (s, 3H), 1.32 ( t, J = 7.60 Hz, 3H)
775[Figure (not displayed)]
MS (ESI) m/z 690.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.52 (s, 1H), 8.29 (s, 1H), 8.04 (s, 1H), 7.86 (s, 1H), 7.59 (dd, J = 8.84, 2.52 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 2.56 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.42 (t, J = 5.76 Hz, 2H), 4.28 (t, J = 4.24 Hz, 2H), 2.73 (s, 3H), 2.43 (s, 3H), 1.87 (s, 3H)
776[Figure (not displayed)]
MS (ESI) m/z 704.04 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 8.06 (s, 1H), 7.92 (t, J = 7.80 Hz, 1H), 7.59 (dd, J = 8.80, 2.40 Hz, 1H), 7.50-7.39 (m, 4H), 7.36 (d, J = 8.88 Hz, 1H), 4.40 (s, 2H), 4.27 (s, 2H), 2.80 (q, J = 7.44 Hz, 2H), 2.72 (s, 3H), 1.84 (s, 3H), 1.22 (q, J = 7.44 Hz, 3H)
777[Figure (not displayed)]
MS (ESI) m/z 693.96 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.85 (dd, J = 5.88, 7.96 Hz, 1H), 8.79 (d, J = 10.04 Hz, 1H), 8.34 (s, 1H), 8.12 (s, 1H), 7.65-7.58 (m, 2H), 7.45 (s, 1H), 7.43 (d, J = 2.56 Hz, 1H), 7.37 (d, J = 8.96 Hz, 1H), 4.45-4.26 (m, 4H), 2.72 (s, 3H), 1.87 (s, 3H)
779[Figure (not displayed)]
MS (ESI) m/z 679.00 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 8.02 (s, 1H), 7.87 (d, J = 1.92 Hz, 1H), 7.59 (dd, J = 8.88, 2.62 Hz, 1H), 7.42 (d, J = 3.0 Hz, 2H), 7.35 (d, J = 8.96 Hz, 1H), 6.48 (s, 1H), 4.40 (t, J = 6.04 Hz, 2H), 4.25 (t, J = 5.2 Hz, 2H), 3.93 (s, 3H), 2.70 (s, 3H), 1.82 (s, 3H)
789[Figure (not displayed)]
MS (ESI) m/z 670.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.24 (s, 1H), 7.97 (s, 1H), 7.56 (dd, J = 8.88, 2.52 Hz, 1H), 7.39-7.37 (m, 2H), 7.31 (d, J = 8.96 Hz, 1H), 4.39-4.34 (m, 2H), 4.22 (bs, 2H), 3.05 (s, 3H), 2.84 (s, 3H), 2.69 (s, 3H), 1.75 (s, 3H)
790[Figure (not displayed)]
MS (ESI) m/z 622.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.95 (s, 1H), 7.59 (dd, J = 8.84, 2.52 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 2.56 Hz, 1H), 7.35 (d, J = 8.96 Hz, 1H), 5.25 (s, 1H), 4.40 (t, J = 4.52 Hz, 2H), 4.25 (t, J = 2.44 Hz, 2H), 2.70 (s, 3H), 1.79 (s, 3H)
808[Figure (not displayed)]
MS (ESI) m/z 506.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34-7.24 (m, 2H), 6.98- 6.93 (m, 2H), 4.49 (t, J = 5.2 Hz, 2H), 4.31 (t, J = 5.2 Hz, 2H), 3.85 (t, J = 12.3 Hz, 2H), 3.53 (d, J = 11.8 Hz, 2H), 3.17 (d, J = 12.9 Hz, 2H), 3.05 (d, J = 11.6 Hz, 2H), 2.88 (s, 3H), 2.77 (s, 3H)
832[Figure (not displayed)]
MS (ESI) m/z = 584.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.85-9.70 (b, 1H), 8.20 (s, 1H), 7.67 (d, J = 2.6 Hz, 1H), 7.40 (dd, J = 8.9, 2.6 Hz, 1H), 7.17 (d, J = 8.9 Hz, 1H), 4.55 (t, J = 4.5 Hz, 2H), 4.39 (t, J = 4.5 Hz, 2H), 3.84 (bt, J = 12.0 Hz, 2H), 3.53 (bd, J = 12.0 Hz, 2H), 3.17 (d, J = 12.5 Hz, 2H), 3.12- 2.97 (m, 2H), 2.92-2.84 (m, 6H)
833[Figure (not displayed)]
MS (ESI) m/z = 582.1 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.84-9.70 (b, 1H), 8.22 (s, 1H), 7.37 (dd, J = 8.8, 2.7, 1H), 7.34- 7.24 (m, 5H), 7.23 (d, J = 2.7 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 4.41-4.30 (m, 4H), 3.86 (bt, J = 12.6 Hz, 2H), 3.54 (bd, J = 11.5 Hz, 2H), 3.18 (d, J = 12.5 Hz, 2H), 3.12-2.99 (m, 2H), 2.89 (bs, 3H), 2.23 (s, 3H)
834[Figure (not displayed)]
MS (ESI) m/z = 683.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.81-9.69 (b, 1H), 8.84 (d, J = 4.7 Hz, 1H), 8.23 (s, 1H), 7.96 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 4.7 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 4.41 (t, J = 5.1 Hz, 2H), 4.25 (t, J = 5.1 Hz, 2H), 3.92-3.82 (m, 2H), 3.57 (bd, J = 11.2 Hz, 2H), 3.26 (bd, J = 13.3 Hz, 2H), 3.15-3.02 (m, 2H), 2.92 (bs, 3H), 1.77 (s, 3H)
835[Figure (not displayed)]
MS (ESI) m/z = 611.3 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.98-9.85 (b, 1H), 8.15 (s, 1H), 7.73-7.64 (bs, 2H), 7.55 (dd, J = 8.9, 2.8 Hz, 1H), 7.46 (d, J = 2.8 Hz, 1H), 7.31 (d, J = 8.9 Hz, 1H), 4.43 (bs, 4H), 3.85 (bt, J = 11.1 Hz, 2H), 3.54 (bd, J = 11.4 Hz, 2H), 3.17 (bd, J = 12.8 Hz, 2H), 3.12- 2.99 (m, 2H), 2.89 (s, 3H), 2.62 (s, 6H), 2.37 (s, 3H)
836[Figure (not displayed)]
MS (ESI) m/z = 653.0 [M + 1]+; 1H-NMR (400 MHz, d6-DMSO) δ/ppm = 9.85-9.74 (b, 1H), 8.06 (s, 1H), 7.70 (d, J = 5.4 Hz, 1H), 7.55 (dd, J = 8.9, 2.6 Hz, 1H), 7.36 (d, J = 2.6 Hz, 1H), 7.32 (d, J = 8.9 Hz, 1H), 7.25 (d, J = 5.4 Hz, 1H), 7.18 (s, 1H), 4.38 (t, J = 4.7 Hz, 2H), 4.28 (t, J = 4.7 Hz, 2H), 3.87 (bt, J = 13 Hz, 2H), 3.56 (bd, J = 11.7 Hz, 2H), 3.25 (bd, J = 13 Hz, 2H), 3.15-3.01 (m, 2H), 2.91 (bs, 3H), 2.62 (s, 3H), 1.96 (s, 3H)
847[Figure (not displayed)]
LCMS: 694.4.5 [M + H]+; 1H NMR (400 MHz, DMSO- d6) δ 8.88 (d, J = 4.8 Hz, 1H), 8.67 (d, J = 2.9 Hz, 1H), 8.29 (s, 1H), 8.13 (s, 1H), 7.89 (dd, J = 9.0, 2.8 Hz, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.43 (q, J = 4.9 Hz, 2H), 4.28 (q, J = 6.6, 5.9 Hz, 2H), 2.22 (s, 3H), 1.79 (s, 3H)
852[Figure (not displayed)]
LCMS: 669.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.59 (d, J = 4.7 Hz, 1H), 8.05 (s, 1H), 7.68 (d, J = 5.5 Hz, 1H), 7.52 (dd, J = 8.9, 2.7 Hz, 1H), 7.38-7.26 (m, 3H), 7.18 (d, J = 4.7 Hz, 1H), 4.35 (t, J = 5.2 Hz, 2H), 4.24 (t, J = 4.9 Hz, 2H), 3.92 (d, J = 12.8 Hz, 2H), 3.76 (t, J = 5.2 Hz, 2H), 3.60 (d, J = 12.0 Hz, 2H), 3.23 (dd, J = 26.4, 8.6 Hz, 4H), 3.09 (s, 3H), 1.86 (s, 3H)
853[Figure (not displayed)]
LCMS: 669.6 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.61 (d, J = 4.7 Hz, 1H), 8.08 (s, 1H), 7.70 (d, J = 5.5 Hz, 1H), 7.52 (dd, J = 8.9, 2.7 Hz, 1H), 7.42-7.34 (m, 2H), 7.29 (d, J = 9.0 Hz, 1H), 7.19 (d, J = 4.7 Hz, 1H), 4.43 (t, J = 5.4 Hz, 2H), 4.35 (t, J = 5.0 Hz, 2H), 4.23 (t, J = 5.0 Hz, 2H), 3.14 (s, 5H), 3.01 (s, 2H), 2.83 (s, 5H), 1.83 (s, 3H)
855[Figure (not displayed)]
MS (ESI) m/z 625.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 27.2 Hz, 2H), 8.62 (d, J = 4.7 Hz, 1H), 8.08 (s, 1H), 7.72 (d, J = 5.5 Hz, 1H), 7.55 (dd, J = 8.9, 2.7 Hz, 1H), 7.44-7.26 (m, 3H), 7.21 (d, J = 4.7 Hz, 1H), 4.38 (t, J = 5.0 Hz, 2H), 4.27 (t, J = 5.0 Hz, 2H), 3.38 (s, 2H), 3.23 (s, 1H), 3.04 (s, 2H), 1.89 (s, 3H)
856[Figure (not displayed)]
LCMS: 720.9 [M + H]+; 1H NMR (400 MHz, DMSO- d6) δ 9.81 (d, J = 9.6 Hz, 1H), 8.59 (s, 1H), 8.09 (s, 1H), 7.79-7.63 (m, 3H), 7.50 (s, 1H), 4.85 (s, 2H), 4.07-3.92 (m, 2H), 3.87-3.74 (m, 2H), 3.66 (d, J = 11.7 Hz, 2H), 3.29 (d, J = 18.2 Hz, 4H), 3.14 (d, J = 11.5 Hz, 2H), 2.67 (s, 3H), 2.23 (s, 3H)
859[Figure (not displayed)]
LCMS: 707.4 [M + H; ]+. 1H NMR (400 MHz, DMSO- d6) δ 9.79 (s, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.11 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.72- 7.66 (m, 2H), 7.57 (d, J = 4.8 Hz, 1H), 4.87 (s, 2H), 3.98 (d, J = 12.8 Hz, 2H), 3.80 (t, J = 5.2 Hz, 2H), 3.72-3.53 (m, 2H), 3.39-3.21 (m, 4H), 3.21- 3.03 (m, 1H), 2.16 (s, 3H)
867[Figure (not displayed)]
MS (ESI) m/z 732.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.91 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.24 (t, J = 5.0 Hz, 2H), 3.98 (t, J = 11.9 Hz, 2H), 3.50 (d, J = 13.5 Hz, 2H), 3.34 (d, J = 13.5 Hz, 2H), 3.18 (d, J = 12.0 Hz, 2H), 2.72 (s, 3H), 1.81 (s, 3H)
870[Figure (not displayed)]
MS (ESI) m/z 650.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.71-8.64 (m, 2H), 8.29 (d, J = 0.6 Hz, 1H), 7.90 (dd, J = 9.2, 3.0 Hz, 1H), 7.78 (d, J = 5.6 Hz, 1H), 7.56 (dd, J = 8.9, 2.7 Hz, 1H), 7.48 (d, J = 5.5 Hz, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.33 (d, J = 8.9 Hz, 1H), 7.26 (d, J = 4.7 Hz, 1H), 4.43-4.35 (m, 2H), 4.34- 4.15 (m, 1H), 2.19 (d, J = 1.0 Hz, 3H), 1.88 (s, 3H)
876[Figure (not displayed)]
LCMS (ESI) m/z 678.8 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.96 (s, 1H), 7.57 (dd, J = 8.9, 2.7 Hz, 1H), 7.43-7.36 (m, 2H), 7.33 (d, J = 9.0 Hz, 1H), 4.38 (t, J = 4.9 Hz, 2H), 4.23 (t, J = 4.9 Hz, 2H), 2.68 (s, 3H), 1.76 (s, 3H)
879[Figure (not displayed)]
LCMS (ESI) m/z 697.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.81 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.49-7.34 (m, 3H), 4.41 (s, 2H), 4.26 (s, 2H), 3.79 (s, 7H), 3.40 (d, J = 12.1 Hz, 2H), 3.18 (d, J = 12.2 Hz, 2H), 3.05 (s, 2H), 2.72 (s, 3H), 2.42 (s, 3H), 1.97 (s, 3H)
887[Figure (not displayed)]
LCMS (ESI) m/z 682.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 11.8 Hz, 1H), 8.76 (d, J = 4.9 Hz, 1H), 8.41 (d, J = 11.5 Hz, 1H), 7.94 (s, 1H), 7.58 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (d, J = 4.9 Hz, 1H), 7.39 (d, J = 2.7 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 5.1 Hz, 2H), 4.22 (t, J = 5.0 Hz, 2H), 3.66 (s, 2H), 3.58 (s, 1H), 3.45 (d, J = 12.3 Hz, 2H), 3.35 (s, 1H), 3.15-3.08 (m, 1H), 3.05 (d, J = 12.2 Hz, 1H), 2.75 (d, J = 13.4 Hz, 2H), 2.30 (s, 3H), 1.85 (d, J = 17.3 Hz, 1H), 1.84 (s, 3H
899[Figure (not displayed)]
MS (ESI) m/z 643.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.90 (s, 1H), 7.57 (dd, J = 8.80, 2.56 Hz, 1H), 7.31-7.30 (m, 2H), 4.41 (t, J = 4.80 Hz, 2H), 4.33 (t, J = 4.80 Hz, 2H), 3.69 (s, 3H), 2.64 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H)
901[Figure (not displayed)]
MS (ESI) m/z 690.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.71 (s, 1H), 8.65 (d, J = 4.60 Hz, 1H), 8.29 (s, 1H), 8.10 (s, 1H), 7.60 (d, J = 8.88, 2.44 Hz, 1H), 7.48 (bs, 1H), 7.46 (s, 1H), 7.44 (d, J = 2.48 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H) 4.42 (t, J = 6.20 Hz, 2H), 4.32-4.22 (m, 2H), 2.73 (s, 3H), 2.07 (s, 3H), 1.84 (s, 3H)
902[Figure (not displayed)]
MS (ESI) m/z 704.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.41 (bs, 1H), 8.45 (s, 1H), 8.25 (s, 1H), 8.08 (s, 1H), 7.63-7.57 (m, 2H), 7.46-7.40 (m, 2H), 7.36 (d, J = 8.80 Hz, 1H), 4.45-4.35 (m, 2H), 4.35-4.23 (m, 2H), 2.72 (s, 3H), 2.35 (s, 3H), 2.15 (s, 3H), 1.83 (s, 3H)
903[Figure (not displayed)]
MS (ESI) m/z 704.16 [M +1]+; 1H NMR (400 MHz, DMSO-d6) 8.46 (s, 1H), 8.30 (s, 1H), 8.24 (s, 1H), 7.84 (bs, 1H), 7.58-7.49 (m, 1H), 7.37 (s, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.16 (s, 1H), 4.37 (t, J = 4.68 Hz, 2H), 4.27 (t, J = 4.2 Hz, 2H), 2.64 (s, 3H), 2.31 (s, 3H), 1.95 (s, 3H), 1.85 (s, 3H)
904[Figure (not displayed)]
MS (ESI) m/z 704.22 [M + 1]+;; 1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.04 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.57 (dd, J = 8.88 Hz, 2.4 Hz, 1H), 7.43 (s, 2H), 7.40-7.34 (m, 2H), 4.40 (t, J = 4.48 Hz, 2H), 4.22 (t, J = 5.2 Hz, 2H), 2.72 (s, 3H), 2.50 (s, 3H), 2.36 (s, 3H), 1.82 (s, 3H)
905[Figure (not displayed)]
MS (ESI) m/z 704.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.04 (s, 1H), 7.59 (dd, J = 8.84 Hz, 2.60 Hz, 1H), 7.43 (s, 2H), 7.36 (d, J = 8.96 Hz, 1H), 7.30 (s, 1H), 7.25 (s, 1H), 4.40 (s, 2H), 4.27 (s, 2H), 2.72 (s, 3H), 2.50 (s, 3H), 2.39 (s, 3H), 1.82 (s, 3H)
906[Figure (not displayed)]
MS (ESI) m/z 704.03 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.52 (bs, 1H), 8.37 (s, 1H), 8.11 (s, 1H), 7.72 (d, J = 7.88 Hz, 1H), 7.59 (dd, J = 8.88, 2.4 Hz, 1H), 7.45-7.43 (m, 2H), 7.36-7.31 (m, 2H), 4.43 (t, J = 4.36 Hz, 2H), 4.26 (t, J = 5.88 Hz, 2H), 2.72 (s, 3H), 2.46 (s, 3H), 2.04 (s, 3H), 1.80 (s, 3H) MS (ESI) m/z 679.00 [M + 1]+; 1H NMR (400 MHz,
907[Figure (not displayed)]
DMSO-d6) δ 13.56 (bs, 1H), 8.40 (s, 1H), 7.99 (s, 1H), 7.77 (s, 1H), 7.58 (d, J = 7.20 Hz, 1H), 7.42-7.34 (m, 4H), 4.39 (s, 2H), 4.25 (s, 2H), 3.77 (s, 3H), 2.69 (s, 3H), 1.82 (s, 3H)
908[Figure (not displayed)]
MS (ESI) m/z 670.97 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.44 (s, 1H) 9.15 (d, J = 5.08 Hz, 1H), 8.64 (s, 1H), 8.27 (s, 1H), 7.97 (d, J = 5 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.67 (m, 1H), 7.65 (d, J = 0.84 Hz, 1H), 7.49 (s, 1H), 4.89 (s, 2H), 2.64 (s, 3H), 2.22 (s, 3H)
909[Figure (not displayed)]
MS (ESI) m/z 684.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.57 (bs, 1H), 8.23 (s, 1H), 7.93 (s, 1H), 7.59 (dd, J = 2.44, 8.84 Hz, 1H), 7.41 (d, J = 2.76 Hz, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.20 Hz, 2H), 4.25 (t, J = 5.88 Hz, 2H), 4.16 (s, 2H), 3.17 (s, 3H), 2.86 (s, 3H), 2.69 (s, 3H), 1.82 (s, 3H)
934[Figure (not displayed)]
MS (ESI) m/z 722.05 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.5 (bs,1H), 8.24 (s, 1H), 8.05 (s, 1H), 7.59 (dd, J = 8.88, 2.4 Hz, 1H), 7.43-7.40 (m, 4H), 7.36 (d, J = 9.2 Hz,1H), 5.55 (d, J = 44 Hz, 2H), 4.41 (t, J = 5.2 Hz, 2H), 4.27 (t, J = 5.2 Hz, 2H), 2.72 (s, 3H), 2.58 (s, 3H), 1.84 (s, 3H)
937[Figure (not displayed)]
MS (ESI) m/z 688.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 8.06 (s, 1H), 7.41-7.35 (m, 2H), 7.25 (dd, J = 8.56, 2.84 Hz, 1H), 4.38 (t, J = 4.48 Hz, 2H), 4.27 (t, J = 4.32 Hz, 2H), 2.72 (s, 3H), 2.63 (s, 6H), 1.90 (s, 3H)
963[Figure (not displayed)]
MS (ESI) m/z 705.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (bs, 1H), 8.33 (s, 1H), 8.07 (s, 1H), 7.60 (dd, J = 2.48, 8.90 Hz, 1H), 7.55 (s, 1H), 7.43-7.42 (m, 2H), 7.36 (d, J = 8.92 Hz, 1H), 4.41 (bs, 2H), 4.27 (bs, 2H), 2.72 (s, 3H), 2.65 (s, 1H), 2.56 (s, 1H), 1.84 (s, 3H)
964[Figure (not displayed)]
MS (ESI) m/z 709.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.57 (bs, 1H), 9.14 (s, 1H), 8.41 (s, 1H), 8.19 (s, 1H), 7.60 (dd, J = 2.56, 8.92 Hz, 1H), 7.44-7.43 (m, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.42 (t, J = 5.20 Hz, 2H), 4.27 (t, J = 4.52 Hz, 2H), 2.73 (s, 3H), 2.70 (s, 3H), 1.82 (s, 3H)
965[Figure (not displayed)]
MS (ESI) m/z 705.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.11 (s, 1H), 7.58 (d, J = 8.84 Hz, 1H), 7.46-7.39 (m, 3H), 7.34 (d, J = 8.88 Hz, 1H), 4.39 (t, J = 4.76 Hz, 2H), 4.26 (t, J = 4.44, Hz, 2H), 2.70 (s, 3H), 2.49 (s, merged, 6H), 1.77 (s, 3H)
966[Figure (not displayed)]
MS (ESI) m/z 695.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.43 (s, 1H) 9.22 (s, 2H), 8.35 (s, 1H), 8.17 (s, 1H), 7.57 (t, J = 6.56 Hz, 1H), 7.42 (d, J = 2.24 Hz, 1H), 7.38 (s, 1H), 7.34 (d, J = 8.88 Hz, 1H), 4.39 (t, J = 2.96 Hz, 2H), 4.27 (t, J = 3.88 Hz, 2H), 2.69 (s, 3H), 1.82 (s, 3H)
967[Figure (not displayed)]
MS (ESI) m/z 691.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.29 (bs, 1H), 8.16 (bs, 1H), 7.94 (bs, 1H), 7.86-7.83 (m, 1H), 7.59 (d, J = 7.16 Hz, 1H), 7.41-7.28 (m, 3H), 4.41 (bs, 2H), 4.30 (bs, 2H), 2.76 (s, 3H), 2.50 (bs, 3H), 1.86 (bs, 3H)
968[Figure (not displayed)]
MS (ESI) m/z 705.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 ) 8.63 (s, 1H), 8.37 (s, 1H), 8.14 (s, 1H), 7.60 (dd, J = 8.88, 2.52 Hz, 1H), 7.48-7.43 (m, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.48-4.35 (m, 2H), 4.30- 4.24 (m, 2H), 2.73 (m, 3H), 2.52 (m, 3H), 2.29 (m, 3H), 1.80 (s, 3H)
969[Figure (not displayed)]
MS (ESI) m/z 705.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.36 (s, 1H), 8.08 (s, 1H), 7.60 (dd, J = 8.80, 2.48 Hz,1H), 7.45-7.42 (m, 2H), 7.36 (d, J = 8.92, 1H), 4.44-4.38 (m, 2H), 4.31-4.23 (m, 2H), 2.72 (s, 3H), 2.66 (s, 3H), 2.57 (s, 3H), 1.84 (s, 3H)
991[Figure (not displayed)]
MS (ESI) m/z 714.06 [M − 1]−; 1H NMR (400 MHz, DMSO-d6) δ 8.29 (s, 1H), 7.90 (s, 1H), 7.59 (dd, J = 8.84, 2.40 Hz, 1H), 7.46-7.40 (m, 2H), 7.36 (d, J = 9.00, 1H), 4.39 (t, J = 4.48 Hz, 2H), 4.23 (t, J = 4.08 Hz, 3H), 3.60-3.40 (m, 2H), 3.20-3.02 (m, 2H), 3.01- 2.80 (m, 1H), 2.70 (s, 3H), 2.30-2.10 (m, 2H), 2.00- 2.82 (m, 2H), 1.81 (s, 3H)
992[Figure (not displayed)]
MS (ESI) m/z 700.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 8.26 (s, 1H), 7.89 (s, 1H), 7.63-7.58 (m, 1H), 7.44-7.39 (m, 2H), 7.36 (d, J = 8.8 Hz, 1H), 4.39 (s, 2H), 4.23 (s, 2H), 3.71-3.50 (m, merged, 2H), 3.31-3.20 (m, 2H), 2.87-.73 (m, 2H), 2.71 (s, 3H), 2.69-2.60 (m. 2H), 1.80 (s, 3H)
995[Figure (not displayed)]
MS (ESI) m/z 744.09 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.20 (bs, 1H), 8.35 (s, 1H), 8.29-8.25 (m, 1H), 8.22 (s, 1H), 8.09-8.06 (m, 1H), 7.57 (d, J = 9.24 Hz, 1H), 7.43-7.33 (m, 3H), 7.07 (t, J = 54.36 Hz, 1H), 4.39 (bs, 2H), 4.27 (bs, 2H), 2.69 (s, 3H), 1.83 (s, 3H)
996[Figure (not displayed)]
MS (ESI) m/z 642.01 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.89 (s, 1H), 7.59 (dd, J = 2.60, 8.88 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.64 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.39 (t, J = 4.68 Hz, 2H), 4.23 (t, J = 4.64 Hz, 2H), 2.94 (s, 6H), 2.70 (s, 3H), 1.81 (s, 3H)
1009[Figure (not displayed)]
MS (ESI) m/z 684.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1H), 8.39 (s, 1H), 7.77 (s, 1H), 7.58 (dd, J = 2.44, 8.84 Hz, 1H), 7.41-7.39 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.65-4.62 (m, 2H), 4.37 (bs, 2H), 4.32-4.27 (m, 3H), 4.18 (bs, 2H), 3.37 (s, 3H), 2.70 (s, 3H), 1.74 (s, 3H)
1012[Figure (not displayed)]
MS (ESI) m/z 690.14 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6): δ 13.74 (s, 1H), 8.71 (d, J = 5.0 Hz, 2H), 8.26 (s,1H), 8.041 (s, 1H), 7.61 (dd, J = 7.2.24 Hz, J = 2.20 Hz,1H), 7.54 (d, J = 4.64 Hz, 2H), 7.48 (s, 1H), 7.44 (d, J = 2.24 Hz, 1H), 7.38 (d, J = 8.88 Hz, 1H), 4.43 (t, J = 4.52 Hz, 2H), 4.27 (t, J = 4.44 Hz, 2H), 3.06 (m, 2H), 1.80 (s, 3H), 1.39 (t, J = 7.52 Hz, 3H)
1013[Figure (not displayed)]
MS (ESI) m/z 690.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 4.12 Hz, 1H), 8.69 (s, 1H), 8.26 (s, 1H), 8.04 (s, 1H), 7.98 (d, J = 7.68 Hz, 1H), 7.65-7.59 (m, 2H), 7.49 (s, 1H), 7.44 (d, J = 2.48 Hz, 1H), 7.38 (d, J = 8.96 Hz, 1H), 4.43 (t, J = 4.52 Hz, 2H), 4.27 (t, J = 4.44 Hz, 2H), 3.06 (m, 2H), 1.80 (s, 3H), 1.39 (t, J = 7.52 Hz, 3H)
1014[Figure (not displayed)]
MS (ESI) m/z 693.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.32 (s, 1H), 8.00 (s, 1H), 7.87 (d, J = 2.56 Hz, 1H), 7.60 (dd, J = 2.56, 8.88 Hz, 1H), 7.46 (s, 1H), 7.44 (d, J = 2.44 Hz, 1H), 7.35 (d, J = 9.00 Hz, 1H), 6.48 (s, 1H), 4.40 (t, J = 4.56 Hz, 2H), 4.24 (t, J = 4.72 Hz, 2H), 3.93 (s, 3H), 3.02 (q, J = 7.36, 2H), 1.76 (s, 3H), 1.35 (t, J = 7.52 Hz, 3H)
1017[Figure (not displayed)]
MS (ESI) m/z 722.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 8.67 (d, J = 2.68 Hz, 1H), 8.22 (s, 1H), 8.08 (s, 1H), 7.90 (d, J = 6.68 Hz, 1H), 7.59 (dd, J = 2.48, 8.92 Hz, 1H), 7.49 (s, 1H), 7.44 (d, J = 2.48 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.41 (t, J = 3.88 Hz, 2H), 4.28 (bs, 2H), 3.04 (q, J = 7.2 Hz, 2H), 2.21 (s, 3H), 1.79 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H)
1025[Figure (not displayed)]
MS (ESI) m/z 727.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (bs, 1H), 9.24 (s, 1H), 9.22 (s, 1H), 8.34 (s, 1H), 8.14 (s, 1H), 7.60 (dd, J = 2.52, 8.84 Hz, 1H), 7.43-7.17 (m, 4H), 4.42 (bs, 2H), 4.28 (bs, 2H), 2.72 (s, 3H), 1.87 (s, 3H)
1026[Figure (not displayed)]
MS (ESI) m/z 745.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 9.49 (s, 1H), 8.36 (s, 1H), 8.15 (s, 1H), 7.61 (dd, J = 2.48, 8.8 Hz, 1H), 7.44- 7.42 (m, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.42 (bs, 2H), 4.30 (bs, 2H), 2.72 (s, 3H), 1.89 (s, 3H)
1027[Figure (not displayed)]
MS (ESI) m/z 693.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 8.04 (s, 1H), 7.65 (s, 1H), 7.59 (dd, J = 8.92 Hz, 1.48 Hz, 1H), 7.44 (s, 2H), 7.36 (s, 1H),4.41 (s, 2H), 4.25 (s, 2H), 3.86 (s, 3H), 2.71 (s, 3H), 1.86 (s, 3H), 1.79 (s, 3H)
1028[Figure (not displayed)]
MS (ESI) m/z 693.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.57 (s, 1H), 8.32 (s, 1H), 8.07 (s, 1H), 7.61 (dd, J = 2.56 Hz, J = 8.88 Hz, 1H), 7.45- 7.43 (m, 2H), 7.37 (d, J = 9.00 Hz, 1H), 6.27 (s, 1H), 4.41 (bs, 3H), 4.27 (bs, 2H), 3.55 (s, 3H), 2.72 (s, 3H), 2.23 (s, 3H), 1.84 (s, 3H)
1029[Figure (not displayed)]
MS (ESI) m/z 693.00 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (bs, 1H), 8.34 (s, 1H), 8.01 (s, 1H), 7.59 (dd, J = 8.88, 2.4 Hz, 1H), 7.43-7.41 (m, 3H), 7.35 (d, J = 8.8 Hz, 1H), 4.40 (t, J = 6.04 Hz, 2H), 4.25 (t, J = 5.2 Hz, 2H), 3.83 (s, 3H), 2.70 (s, 3H), 2.10 (s, 3H), 1.83 (s, 3H)
1030[Figure (not displayed)]
MS (ESI) m/z 693.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (bs, 1H), 8.26 (s, 1H), 8.10 (s, 1H), 7.61 (dd, J1 = 6.48, J2 = 2.28 Hz 1H), 7.45-7.43 (m, 3H), 7.38 (d, J = 8.88 Hz, 1H), 4.42 (bs, 2H), 4.26 (bs, 2H), 3.57 (s, 3H), 2.72 (s, 3H), 1.82 (s, 6H)
1031[Figure (not displayed)]
MS (ESI) m/z 693.13 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.56 (bs, 1H), 8.34 (s, 1H), 8.00 (s, 1H), 7.77 (s, 1H), 7.59 (dd, J = 8.84, 2.40 Hz, 1H), 7.43 (s, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.48-4.36 (m, 2H), 4.35-4.19 (m, 2H), 3.86 (s, 3H), 2.70 (s, 3H), 1.97 (s, 3H), 1.84 (s, 3H)
1032[Figure (not displayed)]
MS (ESI) m/z 693.10 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 8.01 (s, 1H), 7.60 (dd, J = 9.92, 3.32 Hz, 1H), 7.45-7.39 (m, 3H), 7.36 (d, J = 8.88 Hz, 1H), 4.46-4.45 (m, 2H), 4.30-4.20 (m, 2H), 3.83 (s, 3H), 2.70 (s, 3H), 2.10 (s, 3H), 1.83 (s, 3H)
1033[Figure (not displayed)]
MS (ESI) m/z 706.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 4.4 Hz, 1H), 8.28 (s, 1H), 8.00-7.95 (m, 2H), 7.72 (d, J = 7.72 Hz, 1H), 7.60 (dd, J = 8.88, 2.56 Hz, 1H), 7.46-7.39 (m, 3H), 7.37 (d, J = 8.96 Hz, 1H), 5.45 (s, 2H), 4.42 (t, J = 3.8 Hz, 2H), 4.25 (t, J = 4.3 Hz, 2H), 2.72 (s, 3H), 1.80 (s, 3H)
1034[Figure (not displayed)]
MS (ESI) m/z 655.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.54 (bs, 1H), 8.29 (s, 1H), 7.90 (s, 1H), 7.59 (dd, J = 8.92, 2.32 Hz, 1H), 7.42 (s, 2H), 7.36 (d, J = 8.92 Hz, 1H), 4.77-4.70 (m, 1H), 4.40 (t, J = 6.64 Hz, 2H), 4.23 (t, J = 5.12 Hz, 2H), 2.70 (s, 3H), 1.76 (s, 3H), 0.92-0.75 (m, 4H)
1035[Figure (not displayed)]
MS (ESI) m/z 792.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.45 (bs, 1H), 8.44 (d, J = 2.52 Hz, 1H), 8.38 (d, J = 3.32 Hz, 1H), 8.34 (s, 1H), 8.11 (s, 1H), 7.60 (dd, J = 2.55, 8.88 Hz, 1H), 7.49-7.42 (m, 4H), 7.35 (d, J = 8.90 Hz, 1H), 4.41 (t, J = 5.24 Hz, 2H), 4.05 (t, J = 4.0 Hz, 2H), 2.72 (s, 3H), 1.77 (s, 3H)
1036[Figure (not displayed)]
MS (ESI) m/z 629.11 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.91 (s, 1H), 7.60 (dd, J = 8.92, 2.56 Hz, 1H), 7.43 (s, 1H)- 7.42, (d, J = 2.80 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.40 (t, J = 4.72 Hz, 2H), 4.24 (t, J = 4.48 Hz, 2H), 4.13 (s, 3H), 2.71 (s, 3H), 1.78 (s, 3H)
1046[Figure (not displayed)]
MS (ESI) m/z 639.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.90 (s, 1H), 7.59 (dd, J = 8.84, 2.40 Hz, 1H), 7.44-7.39 (m, 2H), 7.35 (d, J = 8.92 Hz, 1H), 4.38 (t, J = 5.56 Hz, 2H), 4.24 (t, J = 6.04 Hz, 2H), 2.69 (s, 3H), 2.30-2.18 (m, 1H) 1.83 (s, 3H), 1.26-1.12 (m, 2 h), 1.00-0.90 (m, 2H)
1049[Figure (not displayed)]
MS (ESI) m/z 639.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.90 (s, 1H), 7.59 (dd, J = 8.84, 2.40 Hz, 1H), 7.44-7.39 (m, 2H), 7.35 (d, J = 8.92 Hz, 1H), 4.38 (t, J = 5.56 Hz, 2H), 4.24 (t, J = 6.04 Hz, 2H), 2.69 (s, 3H), 2.30-2.18 (m, 1H) 1.83 (s, 3H), 1.26-1.12 (m, 2 h), 1.00-0.90 (m, 2H)
1055[Figure (not displayed)]
MS (ESI) m/z 684.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.55 (s, 1H), 8.40 (s, 1H), 7.77 (s, 1H), 7.59 (dd, J = 2.28 Hz, J = 8.84 Hz, 1H), 7.42 (d, J = 2.40 Hz, 1H), 7.40 (s, 1H), 7.35 (d, J = 8.88, 1H), 5.72 (s, 1H), 4.39-4.30 (m, 6H), 4.18 (t, J = 6.68, 2H), 2.70 (s, 3H), 1.73 (s, 3H), 1.45 (s, 3H)
1058[Figure (not displayed)]
MS (ESI) m/z 706.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.49 (bs, 1H), 8.27 (s, 1H), 8.05 (s, 1H), 7.56-7.48 (m, 2H), 7.39 (s, 1H), 4.41 (t, J = 5.52 Hz, 2H), 4.27 (t, J = 5.04 Hz), 2.72 (s, 3H), 2.61 (s, 6H), 1.86 (s, 3H)
1059[Figure (not displayed)]
MS (ESI) m/z 710.5 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 8.57 (d, J = 1.6 Hz, 1H), 8.27 (s, 1H), 8.10-8.03 (m, 2H), 7.79 (d, J = 8.2 Hz,1H), 7.60 (dd, J = 8.8, 2.6 Hz, 1H), 7.45 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 8.9 Hz, 1H), 4.42 (t, J = 4.24 Hz, 2H), 4.28 (t, J = 5.4 Hz, 2H), 2.73 (s, 3H), 1.87 (s, 3H)
1030[Figure (not displayed)]
MS (ESI) m/z 667.06 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.53 (bs, 1H), 8.35 (d, J = 2.68 Hz, 1H), 8.29 (s, 1H), 8.08 (s, 1H), 7.60 (dd, J = 8.84, 2.36 Hz, 1H), 7.46-7.40 (m, 3H), 7.36 (d, J = 8.96 Hz, 1H), 4.50-4.20 (m, 4H), 3.86 (s, 3H), 2.72 (s, 3H), 2.12 (s, 3H), 1.86 (s, 3H)
1073[Figure (not displayed)]
MS (ESI) m/z 643.20 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.91 (s, 1H), 7.59 (dd, J = 8.84 Hz, 2.56 Hz, 1H), 7.43-7.41 (m, 2H), 7.36 (d, J = 8.96 Hz, 1H), 4.40-4.35 (m, 4H), 4.23 (t, J = 4.16 Hz, 2H), 2.70 (s, 3H), 1.78 (s, 3H), 1.46 (t, J = 6.96 Hz, 3H)
1074[Figure (not displayed)]
MS (ESI) m/z 697.14 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 ) 8.21 (s, 1H), 7.96 (s, 1H), 7.59 (d, J = 8.96 Hz, 1H), 7.43 (s, 1H), 7.41 (s, 1H), 7.36 (d, J = 8.96 Hz, 1H), 5.00 (q, J = 8.40 Hz, 2H), 4.41 (t, J = 5.24 Hz, 2H), 4.25 (t, J = 4.8 Hz, 2H), 2.72 (s, 3H), 1.79 (s, 3H)
1075[Figure (not displayed)]
MS (ESI) m/z 711.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 8.06 (s, 1H), 7.59 (d, J = 8.84 Hz, 1H), 7.43 (d, J = 5.5 Hz, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.46-3.64 (m, 10H), 2.82 (s, 3H), 2.71 (s, 3H), 1.85 (s, 3H)
1079[Figure (not displayed)]
MS (ESI) m/z 767.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.00 (d, J = 6.4 Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.33 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.19 (s, 1H), 4.33 (bs, 2H), 4.20 (bs, 2H), 2.54 (s, 3H), 2.19 (s, 3H), 1.67 (s, 3H)
1080[Figure (not displayed)]
MS (ESI) m/z 751.17 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.94 (s, 1H), 7.53 (dd, J = 8.76, 2.16 Hz, 1H), 7.40 (d, J = 2.16 Hz, 1H), 7.29 (d, J = 8.92 Hz, 1H), 7.19 (s, 1H), 7.00 (d, J = 6.52, Hz, 1H), 5.76-5.68 (m, 1H), 4.40-4.30 (m, 2H), 4.30-4.15 (m, 2H), 3.70-3.45 (m, 2H), 3.10-2.70 (m, 2H), 2.60 (s, 3H), 2.35-1.90 (m, 7H), 1.69 (s, 3H)
1081[Figure (not displayed)]
MS (ESI) m/z 805.02 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 2.76 Hz, 1H), 8.26 (s, 1H), 8.12 (s, 1H), 7.97 (d, J = 6.76 Hz, 1H), 7.57 (dd, J = 2.56, 8.8 Hz, 1H), 7.36 (t, J = 2.56 Hz, 2H), 7.28 (s, 1H), 4.41-4.21 (m, 6H), 2.82 (bs, 2H), 2.64 (s, 3H), 2.50 (s, 4H), 2.19 (s, 3H), 1.91 (s, 3H), 1.69 (s, 4H)
1082[Figure (not displayed)]
MS (ESI) m/z, 867.35 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.96 (s, 1H), 7.57 (dd, J = 2.52, 8.88 Hz, 1H), 7.36 (d, J = 2.52 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 7.27 (s, 1H), 6.94-6.90 (m, 1H), 4.61-4.56 (m, 1H), 4.37 (bs, 2H), 4.23 (bs, 2H), 3.60 (bs, 2H), 2.95 (bs, 2H), 2.63 (s, 3H), 2.24 (s, 4H), 1.84 (bs, 2H), 1.75 (s, 3H), 1.63 (d, J = 5.36 Hz, 6H), 1.44-1.39 (m, 4H), 1.33-1.20 (m, 4H)
1085[Figure (not displayed)]
MS (ESI) m/z 711.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.91 (s, 1H), 7.61 (dd, J = 8.9 Hz, 2.44 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.9 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.24 (t, J = 4.0 Hz, 2H), 3.86 (t, J = 9.2 Hz, 2H), 3.55 (bs, 2H), 3.32 (bs, 2H), 3.10 (bs, 2H), 3.02 (q, J = 15.0 Hz, 2H), 2.89 (s, 3H), 1.79 (s, 3H), 1.36 (t, J = 7.5 Hz, 3H)
1087[Figure (not displayed)]
MS (ESI) m/z 725.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.50 (bs, 1H), 7.92 (s, 1H), 7.60 (dd, J = 2.52, 9.28 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.28 Hz, 1H), 7.36 (d, J = 8.88 Hz, 2H), 4.40 (t, J = 5.56 Hz, 2H), 4.24 (t, J = 5.76 Hz, 2H), 3.86 (t, J = 11.28 Hz, 2H), 3.56 (d, J = 11.44 Hz, 2H), 3.21-3.18 (m, 2H), 3.08 (d, J = 10.4 Hz, 2H), 3.01 (q, J = 7.6 Hz, 2H), 2.90 (bs, 3H), 2.37 (s, 3H), 1.90 (s, 3H), 1.36 (t, J = 7.6 Hz, 3H)
1088[Figure (not displayed)]
MS (ESI) m/z 708.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 10.02 (bs,1H), 8.21 (d, J = 5.4 Hz, 1H), 7.97 (d, J = 5.48 Hz, 1H), 7.62 (d, J = 2.28 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 2.24 Hz, 1H), 7.37 (d, J = 8.96 Hz, 1H), 5.95 (s, 1H), 4.42 (bs, 2H), 4.39 (bs, 2H), 4.26 (d, J = 4.55 Hz, 1H), 3.85- 3.65 (m, 2H), 3.4-3.33 (m, 1H), 3.04-2.99 (m, 6H), 2.67 (bs, 1H), 1.86 (s, 3H), 1.36 (t, J = 7.52, 3H)
1093[Figure (not displayed)]
MS (ESI) m/z 697.18 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 4.9 Hz, 1H), 7.95 (s, 1H), 7.61 (dd, J = 2.5, 8.8 Hz, 1H), 7.52 (d, J = 4.8 Hz, 1H), 7.37 (d, J = 2.5 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.3 Hz, 2H), 3.90-3.83 (m, 2H), 3.57-3.54 (m, 2H), 3.21-3.18 (m, 2H), 3.10-3.08 (m, 2H), 2.91 (s, 3H), 2.39 (s, 3H), 1.85 (s, 3H)
1151[Figure (not displayed)]
MS (ESI) m/z 760.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.56 (bs, 1H), 8.89 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), 7.97 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.45-4.38 (m, 2H), 4.26-4.19 (m, 2H), 3.80-3.40 (m, 5H), 3.20-2.75 (m, 4H), 2.65- 2.50 (s, 2H), 2.27 (s, 3H), 1.68 (s, 3H)
1153[Figure (not displayed)]
MS (ESI) m/z 683.16 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 13.12 (bs, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.99 (s, 1H), 7.60 (d, J = 9.2, 2.4 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 5.00 (q, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.25 (s, 2H), 1.73 (s, 3H)
1154[Figure (not displayed)]
MS (ESI) m/z 620.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.79 (bs, 1H), 8.17 (s, 1H), 7.91 (s, 1H), 7.67-7.62 (m, 3H), 7.51 (bs, 2H), 7.37 (bs, 1H), 5.02 (s, 2H), 3.87-3.45 (m, 4H), 3.21-2.91 (m, 4H), 3.02 (bs, 3H), 2.85 (bs, 3H)
1156[Figure (not displayed)]
MS (ESI) m/z 765.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.28 (s, 1H), 7.93 (s, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J = 10.8 Hz, 1H), 4.39 (bs, 2H), 4.23 (bs, 2H), 3.63 (bs, 2H), 3.31 (bs, 2H), 2.95 (m, 4H), 2.60 (t, J = 7.2 Hz, 4H), 1.71 (s, 3H)
1158[Figure (not displayed)]
MS (ESI) m/z 721.16 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.41 (s, 1H), 7.83 (s, 1H), 7.60 (dd, J = 2.4, 8.4 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.71 (s, 2H), 4.63 (s, 2H), 4.40-4.20 (m, 8H), 3.05 (bs, 1H), 1.73 (s, 3H), 0.79-0.77 (m, 4H)
1159[Figure (not displayed)]
MS (ESI) m/z 709.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.4 Hz, 1H), 8.23 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 6.4 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.40 (s, 2H), 4.24 (s, 2H), 3.85 (s, 4H), 3.29 (bs, 4H), 3.12 (bs, 1H), 1.76 (s, 3H), 1.01 (s, 2H), 0.85 (s, 2H)
1178[Figure (not displayed)]
MS (ESI) m/z 715.47 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 5.2 Hz, 1H), 8.66 (s, 1H), 7.93 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 2H), 7.56 (d, J = 4.4 Hz, 1H), 4.82 (s, 2H), 4.73-4.41 (m, 8H), 3.05 (bs, 1H), 2.11 (s, 3H), 0.77 (bs, 4H)
1179[Figure (not displayed)]
MS (ESI) m/z 786.04 [M + 1]+. 1H-NMR (400 MHz, DMSO-d6) δ 12.70 (s, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.31 (s, 1H), 7.97 (s, 1H), 7.63- 7.58 (m, 2H), 7.45 (d, J = 2.40 Hz, 1H), 7.37 (d, J = 9.20 Hz, 1H), 4.42 (bs, 2H), 4.22 (bs, 2H), 3.86-3.66 (m, 4H), 3.57 (s, 3H), 3.28- 3.122 (m, 5H), 1.67 (s, 3H), 2.01-0.84 (m, 4H)
1192[Figure (not displayed)]
MS (ESI) m/z 717.23 [M + 1]+; 1H NMR (400 MHz, DMSO) δ 13.50 (bs, 1H), 8.27 (s, 1H), 8.05 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.59 (dd, J = 8.0, 4.0 Hz, 1H), 7.43 (s, 2H), 7.36 (d, J = 8.0 Hz, 1H), 6.66 (s, 1H), 6.42 (d, J = 4.0 Hz, 1H), 4.41 (s, 2H), 4.26 (s, 2H), 3.46 (t, J = 8.0 Hz, 2H), 2.83-2.60 (m, 5H), 1.84 (s, 3H)
1197[Figure (not displayed)]
MS (ESI) m/z 679.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.46 (bs, 1H), 8.23 (s, 1H), 7.94 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 6.46 (t, J = 52.0 Hz, 1H), 4.70-4.60 (m, 2H), 4.41 (s, 2H), 4.24 (s, 2H), 2.71 (s, 3H), 1.79 (s, 3H)
1200[Figure (not displayed)]
MS (ESI) m/z 684.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.29 (bs, 1H), δ 10.03 (bs, 1H), δ 7.98 (s, 1H), δ 7.61 (dd, J = 9.0 Hz, 2.46 Hz, 1H), 7.43 (s, 1H), 7.42 (s, 1H), 7.35 (d, J = 9.2 Hz, 1H), 4.41 (t, J = 5.1 Hz, 2H), 4.28 (t, J = 4.5 Hz, 2H), 3.42 (bs, 2H), 3.32 (bs, 2H), 2.93 (s, 6H), 2.70 (s, 3H), 2.34 (s, 3H), 1.96 (s, 3H)
1206[Figure (not displayed)]
MS (ESI) m/z 723.34 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 4.6 Hz, 1H), 8.19 (s, 1H), 7.90 (s ,1H), 7.58 (dd, J = 2.48, 8.92 Hz, 1H), 7.38 (d, J = 3.16 Hz, 1H), 7.33 (d, J = 8.96 Hz, 1H), 4.39 (t, J = 5.4 Hz, 2H), 4.22 (t, J = 5.2 Hz, 2H), 3.89 (s, 3H), 3.80-3.40 (m, 4H), 3.10-2.90 (m, 4H), 1.69 (s, 3H), 0.47- 0.35 (m, 4H)
1207[Figure (not displayed)]
MS (ESI) m/z 779.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.32 (bs, 1H), 7.90 (s, 1H), 7.60 (dd, J = 2.6, 8.9 Hz, 1H), 7.41 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.40 (s, 2H), 4.26 (s, 2H), 3.66 (m, 2H), 3.20 (m, 2H), 2.97 (m, 2H), 2.70 (s, 3H), 2.66 (m, 1H), 2.49 (s, 3H), 2.44 (s, 3H), 1.97 (s, 3H)
1212[Figure (not displayed)]
MS (ESI) m/z 677.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.11 (bs, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.11 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.71-7.67 (m, 2H), 7.56 (d, J = 4.8 Hz, 1H), 4.86 (s, 2H), 3.89-3.86 (m, 2H), 3.59-3.56 (m, 2H), 3.29 (d, J = 11.6 Hz, 2H), 3.11 (bs, 2H), 2.92 (s, 3H), 2.17 (s, 3H)
1213[Figure (not displayed)]
MS (ESI) m/z 691.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.77 (s, 1H), 8.58 (s, 1H), 8.09 (s, 1H), 7.76-7.64 (m, 3H), 7.50 (s, 1H), 4.84 (s, 2H), 3.93-3.88 (m, 2H), 3.61-3.58 (m, 2H), 3.32-3.29 (m, 2H), 3.12 (bs, 2H), 2.92 (s, 3H), 2.67 (s, 3H), 2.23 (s, 3H)
1214[Figure (not displayed)]
MS (ESI) m/z 700.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 8.01 (s, 1H), 7.79 (s, 1H), 7.52-7.50 (m, 1H), 7.29-7.20 (m, 4H), 4.34 (bs, 2H), 4.22 (bs, 2H), 3.60-3.38 (m, 2H), 3.25 (bs, 2H), 3.19-2.98 (m, 4H), 2.24 (s, 3H), 1.79 (s, 3H)
1215[Figure (not displayed)]
MS (ESI) m/z 713.31 [M + 1]+;1H NMR (400 MHz, DMSO-d6) δ 13.66 (bs, 1H), 9.74 (bs, 1H), 8.22 (s, 1H), 7.92 (s, 1H), 7.60-7.54 (m, 2H), 7.44 (s, 1H), 4.39 (bs, 2H), 4.23 (bs, 2 H), 3.86 (m, 2H), 3.58 (m, 2H), 3.26-2.98 (m, 6H), 2.89 (s, 3H), 1.79 (s, 3H), 1.35 (t, J = 7.6 Hz, 3H)
1218[Figure (not displayed)]
MS (ESI) m/z 696.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 8.02 (s, 1H), 7.66 (s, 1H), 7.50 (dd, J = 2.4 Hz, J = 8.8 Hz, 1H), 7.27-7.25 (m, 3H), 7.13 (d, J = 7.6 Hz, 1H), 4.34 (t, J = 4.8 Hz, 2H), 4.22 (t, J = 4.8 Hz, 2H), 3.86 (t, J = 10.8, 2H), 3.55-3.53 (m, 2H), 3.24-3.21 (m, 2H), 3.07 (bs, 2H), 2.89 (s, 3H), 2.68 (s, 3H), 1.7 (s, 3H)
1221[Figure (not displayed)]
MS (ESI) m/z 627.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (bs, 1H), 9.72 (bs, 1H), 8.58 (d, J = 4.4 Hz, 1H), 8.15 (s, 1H), 7.90 (s, 1H), 7.54 (d, J = 4.2 Hz, 1H), 7.48 (dd, J = 8.8, 2.5 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 7.25 (d, J = 9.6 Hz, 1H), 4.39 (s, 4H), 3.85 (t, J = 11.3 Hz, 2H), 3.52 (t, J = 11.2 Hz, 2H), 3.21 (d, J = 11.8 Hz, 2H), 3.07 (bs, 2H), 2.89 (s, 3H), 2.24 (s, 3H)
1222[Figure (not displayed)]
MS (ESI) m/z 641.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.73 (bs, 1H), 8.10 (s, 1H), 7.70 (s, 1H), 7.50-7.40 (m, 2H), 7.35 (d, J = 2.8 Hz, 1H), 7.25 (d, J = 9.2 Hz, 1H), 4.38 (s, 4H), 3.85 (t, J = 22.8 Hz, 2H), 3.54 (d, J = 11.2 Hz, 2H), 3.21 (d, J = 11.6 Hz, 2H), 3.13-2.98 (m, 2H), 2.89 (s, 3H), 2.26 (s, 3H)
1223[Figure (not displayed)]
MS (ESI) m/z 655.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.89 (bs, 1H), 9.74 (bs, 1H), 8.10 (s, 1H), 7.72 (s, 1H), 7.48-7.44 (m, 2H), 7.36 (d, J = 2.4 Hz, 1H), 7.24 (d, J = 9.2 Hz, 1H), 4.37 (s, 4H), 4.02- 4.00 (m, 2H), 3.91-3.75 (m, 2H), 3.54 (d, J = 10.4 Hz, 2H), 3.19 (d, J = 12.0 Hz, 2H), 3.15-2.98 (m, 2H), 2.89 (s, 3H), 2.80 (q, J = 8.0 Hz, 2H), 2.29 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H)
1224[Figure (not displayed)]
MS (ESI) m/z 656.30 [M +1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 8.05 (s, 1H), 7.52 (s, 1H), 7.46 (dd, J = 8.8, 2.4 Hz, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.23 (d, J = 8.8 Hz, 1H), 6.95 (s, 1H), 4.36 (bs, 4H), 3.91 (s, 3H), 3.75-3.50 (m, 2H), 3.20-2.70 (m, 6H), 2.26 (s, 3H), 2.24 (s, 3H)
1225[Figure (not displayed)]
MS (ESI) m/z 670.31 [M +1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.39 (bs, 1H), 8.04 (s, 1H), 7.42 (dd, J = 8.0, 4.0 Hz, 1H), 7.28 (d, J = 4.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.09 (s, 1H), 6.63 (s, 1H), 4.34 (s, 4H), 3.82-3.35 (m, 4H), 2.99 (s, 6H), 2.95-2.69 (m, 4H), 2.24 (s, 3H), 2.22 (s, 3H)
1226[Figure (not displayed)]
MS (ESI) m/z 655.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 8.09 (s, 1H), 7.46-7.44 (dd, J = 2.0, 8.8 Hz, 1H), 7.21- 7.16 (m, 2H), 7.08 (s, 1H), 4.30 (bs, 4H), 3.78 (bs, 2H), 3.14 (m, 4H), 2.91 (bs, 2H), 2.74 (s, 3H), 2.45 (s, 3H), 2.02 (s, 3H), 1.88 (s, 3H)
1228[Figure (not displayed)]
MS (ESI) m/z 707.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J = 4 Hz, 1H), 8.19 (s, 1H), 7.68 (s, 1H), 7.60-7.58 (dd, J = 2.4, 8.8 Hz, 1H), 7.45 (t, J = 4 Hz, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.41 (bs, 2H), 4.23 (bs, 2H), 3.86- 2.64 (m, 8H), 2.32 (s, 3H), 1.74 (s, 3H)
1237[Figure (not displayed)]
MS (ESI) m/z 729.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 13.62 (bs, 1H), 7.96 (s, 1H), 7.63-7.60 (dd, J = 2.4, 8.8 Hz, 1H), 7.52 (s, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 5.79 (d, J = 46.4 Hz, 2H), 4.41 (bs, 2H), 4.26 (bs, 2H), 3.89 (t, J = 12.4 Hz, 2H), 3.56 (t, J = 10.4 Hz, 2H), 3.20 (t, J = 12.8 Hz, 2H), 3.09 (bs, 2H), 2.90 (s, 3H), 2.39 (s, 3H), 1.88 (s, 3H)
1238[Figure (not displayed)]
MS (ESI) m/z 741.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 13.98 (bs, 1H), 7.93 (s, 1H), 7.62-7.60 ( m, 1H), 7.48 (s, 1H), 7.43 (bs, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.75 (s, 2H), 4.41 (bs, 2H), 4.25 (bs, 2H), 3.57 (t, J = 12.0 Hz, 2H), 3.44 (bs, 2H), 3.40 (s, 3H), 3.21 (t, J = 10.8 Hz, 2H), 3.10 (bs, 2H), 2.90 (s, 3H), 2.39 (s, 3H), 1.89 (s, 3H)
1239[Figure (not displayed)]
MS (ESI) m/z 733.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.02 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.27 (s, 1H), 7.94 (s, 1H), 7.60 (dd, J = 8.8, 2.8 Hz 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.47-6.19 (m, 1H), 4.40 (s, 2H), 4.24 (s, 2H), 3.70-3.50 (merged, 2H), 3.30-2.80 (m, 8H), 1.75 (s, 3H)
1241[Figure (not displayed)]
MS (ESI) m/z 725.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.77 (bs, 1H), 8.83 (d, J = 4.64 Hz, 1H), 8.24 (s, 1H), 7.96 (s, 1H), 7.11 (dd, J = 8.9 Hz, 2.16 Hz, 1H), 7.48 (d, J = 4.6 Hz, 1H), 7.43 (s, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.74 (bs, 4H), 4.59 (bs, 1H), 4.41 (s, 2H), 4.25 (s, 2H), 4.07 (bs, 2H), 3.54 (bs, 2H), 3.30 (bs, 2H), 2.93 (bs, 2H), 1.76 (s, 3H)
1242[Figure (not displayed)]
MS (ESI) m/z 739.32 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.46 (s, 1H), 8.24 (s, 1H), 7.92 (s, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 6 Hz, 2H), 7.36 (d, J = 8.8 Hz, 1H), 4.78- 4.73 (m, 4H), 4.59 (bs, 1H), 4.40 (s, 2H), 4.25- (s, 2H), 3.91 (bs, 4H), 3.29 (bs, 2H), 2.92 (bs, 2H), 2.72 (s, 3H), 1.84 (s, 3H)
1243[Figure (not displayed)]
MS (ESI) m/z 727.33 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.62 (dd, J = 2.4, 9.2 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.42 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.8 Hz, 2H), 3.95 (bs, 2H), 3.71 (m, 2H), 3.58 (m, 2H), 3.44 (m, 2H), 3.35 (s, 3H), 3.12 (d, J = 10 Hz, 2H), 3.12 (t, J = 10 Hz, 2H), 1.77 (s, 3H)
1244[Figure (not displayed)]
MS (ESI) m/z 663.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.71 (bs, 1H), 8.73 (d, J = 4.4 Hz, 1H), 8.12 (s, 1H), 7.62 (s, 1H), 7.56 (dd, J = 8.8, 2.4 Hz, 1H), 7.38-7.31 (m, 3H), 4.68 (s, 1H), 4.40 (s, 2H), 4.26 (s, 2H), 3.86 (t, J = 12.0 Hz, 2H), 3.54 (d, J = 11.6 Hz, 2H), 3.22 (d, J = 12.8 Hz, 2H), 3.15-3.00 (m, 2H), 2.91 (s, 3H), 1.82 (s, 3H)
1245[Figure (not displayed)]
MS (ESI) m/z 664.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 4.4 Hz, 1H), 8.41 (s, 1H), 8.10 (s, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.56 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 4.43-4.43 (m, 2H), 4.24 (s, 2H), 3.65- 3.49 (m, 2H), 2.99-2.89 (m, 4H), 2.74 (s, 2H), 2.24 (s, 3H), 1.69 (s, 3H)
1246[Figure (not displayed)]
MS (ESI) m/z 673.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.08 (s, 1H), 7.56 (d, J = 7.84, 1H), 7.45 (s, 1H), 7.37-7.31 (m, 3H), 4.40 (s, 2H), 4.27 (s, 2H), 3.72-3.51 (m, 2H), 2.90 (bs, 4H), 2.25 (s, 5H), 1.83 (s, 3H)
1247[Figure (not displayed)]
MS (ESI) m/z 673.19 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.8 Hz, 1H), 8.01 (s, 1H), 7.58 (dd, J = 2.8, 8.8 Hz, 1H), 7.51 (s, 1H), 7.41 (d, J = 4.8 Hz, 1H), 7.37 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 6.8 Hz, 1H), 4.39 (t, J = 4.8 Hz, 2H), 4.24 (t, J = 4.0 Hz, 2H), 3.62 (bs, 2H), 2.81 (bs, 6H), 2.24 (s, 3H),
1248[Figure (not displayed)]
MS (ESI) m/z 653.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.06 (s, 1H), 7.52 (s, 1H), 7.31 (t, J = 9.9 Hz, 2H), 7.13 (s, 1H), 7.06 (s, 1H), 4.36 (s, 2H), 4.26 (s, 2H), 3.91-3.42 (m, 2H), 3.22-2.71 (m, 4H), 2.63- 2.21 (m, 5H), 2.12 (s, 3H), 1.86 (s, 3H)
1249[Figure (not displayed)]
MS (ESI) m/z 653.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.73 (bs, 1H), 8.66 (d, J = 4.8 Hz, 1H), 8.05 (s, 1H), 7.55 (dd, J = 8.8, 2.4 Hz, 1H), 7.34-7.31 (m, 2H), 7.24 (d, J = 4.8 Hz, 1H), 7.13 (s, 1H), 4.41-4.34 (m, 2H), 4.30- 4.20 (m, 2H), 3.87 (t, J = 11.6 Hz, 2H), 3.56 (d, J = 11.6 Hz, 2H), 3.26 (d, J = 12.0 Hz, 2H), 3.15-3.00 (m, 2H), 2.91 (s, 3H), 2.36 (s, 3H), 1.81 (s, 3H)
1250[Figure (not displayed)]
MS (ESI) m/z 640.24 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.74 (bs, 1H), 9.16 (s, 1H), 8.07 (s, 1H), 8.01 (d, J = 5.32 Hz, 1H), 7.62 (dd, J = 8.9, 2.6 Hz, 1H), 7.46 (d, J = 2.6 Hz, 1H) 7.42 (d, J = 5.4 Hz, 1H) 7.36 (d, J = 9.0 Hz, 1H), 4.43 (t, J = 4.9 Hz, 2H), 4.29 (t, J = 4.32 Hz, 2H), 3.87 (t, J = 11.2 Hz, 2H), 3.55 (d, J = 11.6 Hz, 2H), 3.25 (d, 12.36 Hz, 2H), 3.15-3.00 (m, 2H), 2.90 (s, 3H), 1.93 (s, 3H)
1251[Figure (not displayed)]
MS (ESI) m/z 640.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.84 (d, J = 4.5 Hz, 1H), 8.05 (s, 1H), 7.58 (dd, J = 9.0 Hz, 2.5 Hz, 1H), 7.55 (d, J = 4.5 Hz, 1H), 7.47 (d, J = 2.5 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 4.43 (t, J = 4.16 Hz, 2H), 4.27 (t, J = 4.36 Hz, 2H), 3.61 (bs, 4H), 2.96 (bs, 4H), 2.24 (s, 3H), 1.88 (s, 3H)
1252[Figure (not displayed)]
MS (ESI) m/z 667.36 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 4.7 Hz, 1H),), 8.01 (s, 1H), 7.54-7.51 (dd, J = 8.8, J = 2.5 Hz, 1H), 7.30 (m, 2H), 7.18 (d, J = 4.6 Hz, 1H), 4.37 (t, J = 12.7 Hz, 2H), 4.23 (t, J = 3.4 Hz, 2H), 3.64 (m, 4H), 2.89 (m, 4H), 2.23 (s, 6H), 1.97 (s, 3H), 1.79 (s, 3H)
1253[Figure (not displayed)]
MS (ESI) m/z 671.22 [M +1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.78 (d, J = 5.6 Hz, 1H), 7.57 (dd, J = 2.80, 8.8 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 9.6 Hz, 1H), 7.34-7.31 (m, 2H), 5.59 (d, J = 46.8 Hz, 2H), 4.36 (t, J = 4.4 Hz, 2H), 4.25 (t, J = 4.0 Hz, 2H), 3.61 (bs, 2H), 2.93 (bs, 2H), 2.50 (bs, 2H), 2.25 (bs, 5H), 1.85 (s, 3H)
1254[Figure (not displayed)]
MS (ESI) m/z 664.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.48 (s, 1H), 8.03 (s, 1H), 7.61 (dd, J = 2.4, 11.2 Hz, 1H), 7.50 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 4.40 (bs, 2H), 4.26 (bs, 2H), 3.57 (m, 2H), 3.02 (m, 4H), 2.60 (m, 2H), 2.24 (s, 3H), 1.76 (s, 3H)
1255[Figure (not displayed)]
MS (ESI) m/z 612.23 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.99 (bs, 1H), 68.63 (d, J = 4.8 Hz, 1H), 68.10 (s, 1H), 7.66 (d, J = 5.6 Hz, 1H), 7.54 (dd, J = 8.7 Hz, 2.5 Hz, 1H), 7.37 (d, J = 2.4 Hz, 1H), 7.33-31 (m, 2H), 7.21 (d, J = 4.4 Hz, 1H), 4.37 (t, J = 5.1 Hz, 2H), 4.27 (t, J = 4.5 Hz, 2H), 3.45-3.43 (m, 2H), 3.32 (bs, 2H), 2.95 (s, 6H), 1.96 (s, 3H)
1256[Figure (not displayed)]
MS (ESI) m/z 653.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 4.8 Hz, 1H), 8.05 (s, 1H), 7.72 (d, J = 5.6 Hz, 1H), 7.55 (dd, J = 2.4, 8.8 Hz, 1H), 7.42 (d, J = 5.6, Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 7.22 (d, J = 4.4 Hz, 1H), 4.38 (t, J = 4.4 Hz, 2H), 4.25 (t, J = 5.2 Hz, 2H), 3.85 (s, 2H), 2.47 (m, 4H), 2.27 (m, 4H), 1.83 (s, 3H), 1.23 (s, 3H)
1259[Figure (not displayed)]
MS (ESI) m/z 666.25 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 4.0 Hz 1H), 8.20 (s, 1H), 8.02 (s, 1H), 7.58 (d, J = 6.4 Hz, 1H), 7.42 (d, J = 9.2 Hz, 2H), 7.33 (d, J = 8.8 Hz 1H), 4.39 (s, 2H), 4.23 (s, 2H), 3.67 (s, 2H), 2.32 (s, 6H), 1.68 (s, 3H)
1260[Figure (not displayed)]
MS (ESI) m/z 638.08 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.47 (bs, 3H), 8.31 (s, 1H), 8.04 (s, 1H), 7.61 (dd, J = 8.8, 2.4 Hz, 1H), 7.49 (d, J = 4.4 Hz, 1H), 7.44 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 4.41 (bs, 2H), 4.27 (bs, 4H), 1.74 (s, 3H)
1261[Figure (not displayed)]
MS (ESI) m/z 713. 27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 9.60 (bs, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.21 (s, 1H), 7.95 (s, 1H), 7.61 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 5.69 (bs, 1H), 4.41 (s, 2H), 4.24 (s, 2H), 3.95-3.89 (m, 3H), 3.63-3.58 (m, 2H), 3.22-3.30 (m, 6H), 2.96-2.89 (m, 4H), 1.75 (s, 3H)
1262[Figure (not displayed)]
MS (ESI) m/z 749.29 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.37 (bs, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.24 (s, 1H), 7.94 (s, 1H), 7.59 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.40 (s, 2H), 4.23 (s, 2H), 3.96 (m, 2H), 3.48 (m, 4H), 3.24 (m, 1H), 2.96 (s, 3H), 1.72 (s, 3H)
1263[Figure (not displayed)]
MS (ESI) m/z 682.0 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.90 (s, 1H), 7.63-7.56 (m, 1H), 7.46-7.38 (m, 2H), 7.35 (d, J = 8.96 Hz, 1H), 4.49-4.32 (m, 2H), 4.31-4.18 (m, 2H), 3.70-3.66 (m, 1H), 3.26-3.22 (m, 2H), 2.69 (s, 3H), 2.32-2.22 (m, 2H), 2.22-2.09 (m, 2H), 2.07 (s, 3H), 1.80 (s, 3H)
1269[Figure (not displayed)]
MS (ESI) m/z 699.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.12 (bs, 1H), 8.94 (s, 1H), 8.91 (d, J = 4.8 Hz, 1H), 8.15 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.57 (d, J = 4.4 Hz, 1H), 7.49 (bs, 2H), 4.18 (t, J = 6.0 Hz, 2H), 3.87 (bs, 2H), 3.54 (d, J = 12.4 Hz, 2H), 3.33 (bs, 2H), 3.22 (d, J = 11.6 Hz, 2H), 3.08 (bs, 2H), 2.90 (s, 3H), 2.52 (s, 3H)
1270[Figure (not displayed)]
MS (ESI) m/z 691.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.11 (bs, 1H), 8.7 (d, J = 4.7 Hz, 1H), 8.62 (s, 1H), 8.26 (s, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.72-7.66 (m, 2H), 7.25 (d, J = 4.7 Hz, 1H), 5.01- 4.45 (m, 2H), 4.20-3.82 (m, 4H), 3.70-3.45 (m, 2H), 2.88 (s, 3H), 2.16 (s, 3H)
1271[Figure (not displayed)]
MS (ESI) m/z 691.28 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 13.75 (bs, 1H), 9.75 (bs, 1H), 8.74 (d, J = 4.8 Hz, 1H), 8.11 (s, 1H), 7.76-7.69 (m, 2H), 7.65 (s, 1H), 7.58 (d, J = 4.8 Hz, 1H), 4.86 (s, 2H), 3.89 (t, J = 22.4 Hz, 2H), 3.59 (d, J = 11.2 Hz, 2H), 3.30 (d, J = 11.2 Hz, 2H), 3.11 (d, J = 8 Hz, 2H), 2.92 (bs, 3H), 2.64 (s, 3H), 2.22 (s, 3H)
1272[Figure (not displayed)]
MS (ESI) m/z 711.31 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.8 (d, J = 4.8 Hz, 1H), 8.09 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.50 (d, J = 4.8 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.8 Hz 1H), 4.42 (bs, 2H), 4.28 (bs, 2H), 4.08-3.55 (m, 6H), 2.87 (s, 3H), 2.37 (s, 3H), 1.82 (s, 3H)
1275[Figure (not displayed)]
MS (ESI) m/z 724.28 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) 13.73 (bs, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.62-7.59 (dd, J = 2.8, 9.2 Hz, 1H), 7.47-7.44 (m, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.41 (bs, 2H), 4.24 (bs, 2H), 3.43-3.40 (m, 2H), 3.23-2.86 (m, 6H), 2.73 (s, 3H), 2.02 (bs, 1H), 1.79 (bs, 5H), 1.64-1.55 (m, 2H), 1.37 (t, J = 7.6 Hz, 3H)
1276[Figure (not displayed)]
MS (ESI) m/z 710.27 [M + 1]+; ; 1H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 8.45 (bs, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.61-7.59 (dd, J = 6.8, 8.8 Hz, 1H), 7.46-7.43 (m, 2H), 7.37 (d, J = 8.8 Hz, 1H), 4.41 (bs, 2H), 4.24 (bs, 2H), 3.30 (m, 2H), 3.06-2.98 (m, 4H), 2.84 (m, 2H), 2.08 (bs, 1H), 1.79 (s, 3H), 1.75 (d, J = 13.6 Hz, 2H), 1.60 (t, J = 10.0 Hz, 2H), 1.37 (t, J = 7.6 Hz, 3H)
1283[Figure (not displayed)]
MS (ESI) m/z 682.22 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 14.06 (bs, 1H), 8.79 (d, J = 5.2 Hz, 1H), 7.97 (d, J = 5.2 Hz, 1H), 7.61 (dd, J = 2.8, 9.2 Hz, 1H), 7.52 (d, J = 4.8 Hz, 1H), 7.9 (d, J = 2.4 Hz, 1H), 7.38 (d, J = 9.2 Hz, 1H), 4.42 (bs, 2H), 4.27 (bs, 2H), 4.20 (d, J = 6.0 Hz, 2H), 4.02 (d, J = 8.0 Hz, 2H), 3.95 (bs, 1H), 3.38 (d, J = 5.6 Hz, 2H), 2.85 (d, J = 4.8 Hz, 3H), 2.33 (s, 3H), 1.88 (s, 3H)
1286[Figure (not displayed)]
MS (ESI) m/z 714.39 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.23 (bs, 1H), 8.14 (s, 1H), 7.52 (dd, J = 8.8 Hz, 2.5 Hz, 1H), 7.27-7.25 (m, 2H), 7.23- 7.21 (m, 2H), 4.34-4.33 (m, 2H), 4.27-4.25 (m, 2H), 3.87 (t, J = 12.3 Hz, 2H), 3.55-3.53 (m, 2H), 3.18- 3.15 (m, 2H), 3.08-3.06 (m, 2H), 2.89 (s, 3H), 2.04 (s, 3H), 1.83 (s, 3H)
1287[Figure (not displayed)]
MS (ESI) m/z 704.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.8 Hz, 1H), 8.20 (s, 1H), 7.98 (s, 1H), 7.60 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.49 (d, J = 4.4 Hz, 1H), 7.42-7.36 (m, 2H), 4.41 (bs, 6H), 4.24 (s, 2H), 3.31 (d, J = 6.4 Hz, 2H), 3.21 (d, J = 4.8 Hz, 2H), 1.81 (s, 3H)
1288[Figure (not displayed)]
MS (ESI) m/z 706.37 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.4 Hz 1H), 8.21 (s, 1H), 7.98 (s, 1H) 7.59 (dd, J = 8.9, 2.6 Hz, 1H), 7.49 (d, J = 4.8 Hz 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 6.18-6.46 (m, 1H), 4.41 (t, J = 6.02 Hz, 2H), 4.25 (t, J = 8.0 Hz, 2H), 3.39 (s, 4H), 3.09 (s, 2H), 2.73 (s, 3H), 1.77 (s, 3H)
1259[Figure (not displayed)]
MS (ESI) m/z 620.27 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.79 (bs, 1H), 8.17 (s, 1H), 7.91 (s, 1H), 7.67-7.62 (m, 3H), 7.51 (bs, 2H), 7.37 (bs, 1H), 5.02 (s, 2H), 3.87-3.45 (m, 4H), 3.21-2.91 (m, 4H), 3.02 (bs, 3H), 2.85 (bs, 3H)
1291[Figure (not displayed)]
MS (ESI) m/z 709.12 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 4.4 Hz, 1H), 8.23 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 6.4 Hz, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.40 (s, 2H), 4.24 (s, 2H), 3.85 (s, 4H), 3.29 (bs, 4H), 3.12 (bs, 1H), 1.76 (s, 3H), 1.01 (s, 2H), 0.85 (s, 2H)
1292[Figure (not displayed)]
MS (ESI) m/z 759.38 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.30 (bs, 1H), 8.83 (d, J = 4.8 Hz, 1H), 8.25 (s, 1H), 7.96 (s, 1H), 7.60 (dd, J = 6.4, 9.2 Hz, 1H), 7.47 (d, J = 4.8 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.40 (s, 2H), 4.24 (s, 2H), 3.85-3.52 (m, 5H), 3.02 (m, 8H), 1.75 (m, 3H)
1293[Figure (not displayed)]
MS (ESI) m/z 765.30 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 8.82 (d, J = 4.8 Hz, 1H), 8.28 (s, 1H), 7.93 (s, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J = 10.8 Hz, 1H), 4.39 (bs, 2H), 4.23 (bs, 2H), 3.63 (bs, 2H), 3.31 (bs, 2H), 2.95 (m, 4H), 2.60 (t, J = 7.2 Hz, 4H), 1.71 (s, 3H)
1298[Figure (not displayed)]
MS (ESI) m/z 650.26 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 13.06 (bs, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.57 (s, 1H), 8.14 (s, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.70-7.66 (m, 2H), 7.55 (d, J = 4.8 Hz, 1H), 4.88 (s, 2H), 3.38-3.23 (m, 4H), 3.18-3.08 (m, 2H), 2.78 (s, 6H), 2.16 (s, 3H)
1372[Figure (not displayed)]
MS (ESI) m/z 606.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (dd, J = 5.0, 0.8 Hz, 1H), 8.38 (d, J = 1.7 Hz, 1H), 8.26 (dd, J = 1.7, 0.8 Hz, 1H), 8.03 (dd, J = 1.7, 0.8 Hz, 1H), 7.70 (dd, J = 5.0, 1.8 Hz, 1H), 7.57-7.39 (m, 2H), 7.27 (d, J = 8.9 Hz, 1H), 4.40 (s, 4H), 3.39 (s, 3H), 2.23 (s, 3H)
1374[Figure (not displayed)]
MS (ESI) m/z 628.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 1.7 Hz, 1H), 8.25 (s, 3H), 7.99 (d, J = 1.7 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (s, 1H), 7.39-7.34 (m, 2H), 4.41 (d, J = 5.1 Hz, 2H), 4.27 (t, J = 5.1 Hz, 2H), 3.41 (d, J = 6.0 Hz, 2H), 3.28 (t, J = 6.5 Hz, 2H), 1.83 (s, 3H)
1375[Figure (not displayed)]
MS (ESI) m/z 624.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.83 (d, J = 4.7 Hz, 1H), 8.34 (d, J = 1.6 Hz, 1H), 7.95 (s, 1H), 7.81 (d, J = 1.6 Hz, 1H), 7.59 (dd, J = 8.9, 2.7 Hz, 1H), 7.45-7.39 (m, 2H), 7.35 (d, J = 9.0 Hz, 1H), 6.92 (s, 1H), 4.40 (d, J = 5.0 Hz, 2H), 4.25 (t, J = 4.9 Hz, 2H), 1.74 (s, 3H)
1376[Figure (not displayed)]
MS (ESI) m/z 714.3 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.95 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.46-7.40 (m, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.40 (d, J = 5.0 Hz, 2H), 4.25 (s, 2H), 3.91 (s, 2H), 2.70 (s, 5H), 2.58 (s, 2H), 1.83 (s, 3H)
1377[Figure (not displayed)]
MS (ESI) m/z 746.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 8.16 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45-7.34 (m, 3H), 5.49 (d, J = 22.9 Hz, 2H), 4.58 (t, J = 13.1 Hz, 2H), 4.42 (s, 2H), 4.29 (s, 2H), 3.82 (s, 2H), 2.72 (s, 3H), 1.84 (s, 3H)
1380[Figure (not displayed)]
MS (ESI) m/z 690.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.60-8.48 (m, 1H), 8.37 (s, 1H), 8.12 (s, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.60 (dd, J = 8.9, 2.8 Hz, 1H), 7.52-7.42 (m, 3H), 7.36 (d, J = 9.0 Hz, 1H), 4.50-4.34 (m, 2H), 4.27 (d, J = 5.4 Hz, 2H), 2.72 (s, 3H), 2.10 (s, 3H), 1.81 (s, 3H)
1381[Figure (not displayed)]
MS (ESI) m/z 694.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.76-8.65 (m, 1H), 8.34 (s, 1H), 8.14 (s, 1H), 7.73 (t, J = 5.5 Hz, 1H), 7.60 (dd, J = 8.9, 2.6 Hz, 1H), 7.49-7.40 (m, 2H), 7.37 (d, J = 9.0 Hz, 1H), 4.50-4.18 (m, 4H), 2.72 (s, 3H), 1.87 (s, 3H)
1383[Figure (not displayed)]
MS (ESI) m/z 708.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 8.28 (s, 1H), 8.05 (s, 1H), 7.98-7.90 (m, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.47-7.40 (m, 2H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.29 (d, J = 4.9 Hz, 2H), 2.73 (s, 3H), 2.58 (d, J = 2.9 Hz, 3H), 1.88 (s, 3H)
1384[Figure (not displayed)]
MS (ESI) m/z 728.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 9.9 Hz, 1H), 8.31 (s, 1H), 8.13 (s, 1H), 8.03 (d, J = 9.1 Hz, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.53-4.20 (m, 4H), 2.72 (s, 3H), 1.88 (s, 3H)
1388[Figure (not displayed)]
MS (ESI) m/z 708.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.63-8.59 (m, 1H), 8.33 (s, 1H), 8.11 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.50 (d, J = 10.7 Hz, 1H), 7.45 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.53-4.02 (m, 4H), 2.72 (s, 3H), 2.62 (s, 3H), 1.85 (s, 3H)
1389[Figure (not displayed)]
MS (ESI) m/z 706.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 9.47 (s, 1H), 9.18 (s, 1H), 8.23 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.49 (s, 1H), 7.41 (d, J = 9.0 Hz, 1H), 7.30 (d, J = 2.7 Hz, 1H), 7.19 (s, 1H), 4.53 (t, J = 5.2 Hz, 2H), 4.15 (t, J = 5.2 Hz, 2H), 2.67 (d, J = 0.7 Hz, 3H), 2.33 (s, 3H), 2.29 (s, 3H)
1391[Figure (not displayed)]
MS (ESI) m/z 711.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.93 (s, 1H), 7.58 (dd, J = 8.9, 2.7 Hz, 1H), 7.39-7.31 (m, 2H), 7.28 (s, 1H), 4.40 (s, 2H), 4.26 (s, 2H), 3.87 (s, 5H), 3.57 (d, J = 11.7 Hz, 2H), 3.27 (d, J = 12.9 Hz, 2H), 3.09 (d, J = 10.7 Hz, 2H), 2.91 (d, J = 4.2 Hz, 3H), 2.66 (s, 3H), 1.83 (s, 3H)
1392[Figure (not displayed)]
MS (ESI) m/z 740.9 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 5.35 (s, 1H), 4.41 (t, J = 5.0 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 3.97 (t, J = 12.1 Hz, 2H), 3.79 (t, J = 5.2 Hz, 2H), 3.64 (d, J = 11.8 Hz, 2H), 3.15 (dd, J = 29.0, 12.1 Hz, 4H), 2.71 (s, 3H), 2.43 (s, 3H), 1.97 (s, 3H)
1393[Figure (not displayed)]
[01858] MS (ESI) m/z 741.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 2H), 7.93 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.43 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.6 Hz, 4H), 4.26 (t, J = 5.0 Hz, 2H), 3.16 (s, 4H), 3.00 (s, 2H), 2.82 (s, 4H), 2.70 (s, 3H), 2.40 (s, 3H), 1.92 (s, 3H)
1394[Figure (not displayed)]
MS (ESI) m/z 696.4 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 9.59 (s, 1H), 8.15 (d, J = 5.8 Hz, 1H), 7.94 (d, J = 2.2 Hz, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.47 (s, 1H), 7.44 (d, J = 2.6 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.42 (t, J = 5.0 Hz, 2H), 4.35-4.18 (m, 3H), 4.01 (dt, J = 22.5, 10.9 Hz, 2H), 3.11 (d, J = 8.1 Hz, 1H), 3.01 (q, J = 7.5 Hz, 2H), 2.86 (dd, J = 11.5, 5.1 Hz, 2H), 1.81 (s, 3H), 1.36 (t, J = 7.5 Hz, 3H)
1416[Figure (not displayed)]
MS (ESI) m/z 711.0 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.93 (s, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 4.40 (t, J = 4.9 Hz, 2H), 4.26 (t, J = 5.0 Hz, 2H), 3.86 (t, J = 12.3 Hz, 2H), 3.56 (d, J = 11.4 Hz, 3H), 3.20 (d, J = 12.6 Hz, 2H), 3.09 (q, J = 11.2 Hz, 2H), 2.95-2.87 (m, 3H), 2.71 (s, 3H), 2.42 (s, 3H), 1.96 (s, 3H)
1417[Figure (not displayed)]
MS (ESI) m/z 708.1 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.04-7.95 (m, 1H), 7.61 (dd, J = 8.9, 2.7 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 2.7 Hz, 1H), 7.37 (d, J = 9.0 Hz, 1H), 6.54 (s, 1H), 5.91 (s, 1H), 4.42 (t, J = 5.1 Hz, 2H), 4.34- 4.21 (m, 2H), 4.13 (d, J = 17.4 Hz, 1H), 3.84 (d, J = 16.9 Hz, 1H), 3.70-3.57 (m, 1H), 3.40-3.27 (m, 1H), 3.02-2.89 (m, 3H), 2.71 (s, 3H), 2.64 (s, 1H), 2.41 (s, 3H), 1.98 (s, 3H)
1420[Figure (not displayed)]
MS (ESI) m/z 723.2 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 7.78 (s, 1H), 7.60 (dd, J = 8.9, 2.7 Hz, 1H), 7.42-7.40 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 4.70 (s, 2H), 4.61 (s, 2H), 4.49-4.39 (m, 2H), 4.38 (t, J = 5.0 Hz, 2H), 4.27-4.17 (m, 4H), 2.82 (d, J = 5.2 Hz, 3H), 2.70 (s, 3H), 1.92 (s, 3H)
1570[Figure (not displayed)]
MS (ESI) m/z 715.47 [M + 1]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 5.2 Hz, 1H), 8.66 (s, 1H), 7.93 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.70-7.66 (m, 2H), 7.56 (d, J = 4.4 Hz, 1H), 4.82 (s, 2H), 4.73-4.41 (m, 8H), 3.05 (bs, 1H), 2.11 (s, 3H), 0.77 (bs, 4H)
1612[Figure (not displayed)]
MS (ESI) m/z 775.53 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.75 (d, J = 4.68 Hz 1H), 8.10 (d, J = 9.44 Hz, 1H), 8.03 (s, 1H), 7.53 (dd, J = 2.56, 8.92 Hz, 1H), 7.34 (d, J = 2.60 Hz, 1H), 7.31 (d, J = 4.68 Hz, 1H), 7.27 (d, J = 9.0 Hz, 1H), 4.35 (bs, 2H), 4.25-4.20 (m, 6H), 3.55 (bs, 2H), 2.93 (bs, 2H), 2.50 (bs, 2H), 2.20 (s, 5H), 1.58 (s, 3H), 1.27 (t, J = 7.04 Hz, 6H)
1613[Figure (not displayed)]
MS (ESI) m/z 719.52 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.60 (d, J = 4.00 Hz 1H), 8.14 (s, 1H), 7.97 (d, J = 8.80 Hz, 1H), 7.49 (dd, J = 2.40, 8.80 Hz, 1H), 7.34 (d, J = 2.00 Hz, 1H), 7.24 (d, J = 9.20 Hz, 1H), 7.13 (d, J = 4.80 Hz, 1H), 4.32 (bs, 2H), 4.21 (bs, 2H), 3.67 (bs, 2H), 3.11 (bs, 4H), 2.76 (bs, 2H), 2.59 (s, 3H), 1.74 (s, 3H)
1614[Figure (not displayed)]
MS (ESI) m/z 801.60 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.75 (d, J = 4.80 Hz, 1H), 8.09 (d, J = 9.60 Hz, 1H), 8.03 (s, 1H), 7.53 (dd, J = 2.40, 8.80 Hz, 1H), 7.33- 7.30 (m, 2H), 7.26 (d, J = 8.80 Hz, 1H), 4.34 (s, 2H), 4.23-4.19 (m, 6H), 3.50 (bs, 2H), 2.79 (bs, 5H), 1.67 (bs, 2H), 1.58 (s, 3H), 1.27 (t, J = 6.80 Hz, 6H), 0.43 (bs, 2H), 0 .35 (bs, 2H)
1615[Figure (not displayed)]
MS (ESI) m/z 745.50 [M + 1]+; 1H NMR (400 MHz, DMSO-d6 with D20) δ 8.63 (d, J = 4.80 Hz, 1H), 8.12 (s, 1H), 7.98 (d, J = 8.80 Hz, 1H), 7.49 (dd, J = 2.40, 8.80 Hz, 1H), 7.32 (d, J = 2.40 Hz, 1H), 7.23 (d, J = 9.20 Hz, 1H), 7.14 (d, J = 4.4 Hz, 1H), 4.31 (s, 2H), 4.20 (s, 2H), 3.49 (bs, 3H), 2.84 (bs, 4H), 1.75 (bs, 2H), 1.70 (s, 3H), 0.44 (d, J = 6.00 Hz, 2H), 0.38 (bs, 2H)
1619[Figure (not displayed)]
MS (ESI) m/z 642.01[M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.89 (s, 1H), 7.59 (dd, J = 2.60, 8.88 Hz, 1H), 7.43 (s, 1H), 7.42 (d, J = 2.64 Hz, 1H), 7.36 (d, J = 8.96 Hz, 1H), 4.39 (t, J = 4.68 Hz, 2H), 4.23 (t, J = 4.64 Hz, 2H), 2.94 (s, 6H), 2.70 (s, 3H), 1.81 (s, 3H)
1899[Figure (not displayed)]
MS (ESI) m/z 571 [M + 1]; 1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.43 (d, J = 16.6 Hz, 2H), 8.11 (s, 1H), 7.79 (bs, 1H), 7.60 (s, 1H), 7.46 (m, 2H), 7.35 (m, 1H), 4.40 (s, 2H), 4.20 (s, 2H), 3.89 (s, 1H)
1900[Figure (not displayed)]
MS (ESI) m/z 599.1 [M + 1]
1901[Figure (not displayed)]
MS (ESI) m/z 579.15 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 4.48 Hz, 1H), 8.59 (s, 1H), 8.41 (s, 1H), 8.14 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 6.04 Hz, 2H), 7.56 (d, J = 4.48 Hz, 1H), 4.88 (s, 2H), 2.10 (s, 3H)
1902[Figure (not displayed)]
MS (ESI) m/z 627.8 [M + 1]+
1903[Figure (not displayed)]
MS (ESI) m/z 603.21 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 4.8 Hz, 1H), 8.38 (bs, 1H), 8.28 (s, 1H), 8.01 (bs, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 11.4 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 4.43 (t, J = 4.4 Hz, 2H), 4.25 (t, J = 4.4 Hz, 2H), 1.73 (s, 3H)
1904[Figure (not displayed)]
MS (ESI) m/z 619.07 [M + 1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 4.4 Hz, 1H), 8.24 (s, 1H), 8.08 (s, 1H), 7.60 (dd, J = 8.8, 2.6 Hz, 1H), 7.51 (d, J = 4.8 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 4.41 (t, J = 4.7 Hz, 2H), 4.25 (t, J = 4.7 Hz, 2H), 1.69 (s, 3H)
1905[Figure (not displayed)]
MS (ESI) m/z 633.04 [M + 1]+
1906[Figure (not displayed)]
1907[Figure (not displayed)]
MS (ESI) m/z 656.15 [M + 1]
1908[Figure (not displayed)]
MS (ESI) m/z 724.6 [M + 1]+
1909[Figure (not displayed)]
MS (ESI) m/z 708.1 [M + 1]+
1910[Figure (not displayed)]
MS (ESI) m/z 690.3 [M + 1]+
1911[Figure (not displayed)]
MS (ESI) m/z 722.0 [M + 1]+
1912[Figure (not displayed)]
MS (ESI) m/z 773.3 [M + 1]+
1913[Figure (not displayed)]
MS (ESI) m/z 850.3 [M + 1]+
1914[Figure (not displayed)]
1915[Figure (not displayed)]
1916[Figure (not displayed)]
1917[Figure (not displayed)]
1918[Figure (not displayed)]
1919[Figure (not displayed)]
1920[Figure (not displayed)]
1921[Figure (not displayed)]
1922[Figure (not displayed)]
1923[Figure (not displayed)]
1924[Figure (not displayed)]
1925[Figure (not displayed)]
1926[Figure (not displayed)]
1927[Figure (not displayed)]
1928[Figure (not displayed)]
1929[Figure (not displayed)]
1930[Figure (not displayed)]
1931[Figure (not displayed)]
1932[Figure (not displayed)]
1933[Figure (not displayed)]
1934[Figure (not displayed)]
1994[Figure (not displayed)]
2015[Figure (not displayed)]
2016[Figure (not displayed)]
2018[Figure (not displayed)]
2019[Figure (not displayed)]
MS (ESI) m/z 626.05 [M + 1]+
2028[Figure (not displayed)]
MS (ESI) m/z 624.0 [M + 1]+
2036[Figure (not displayed)]
MS (ESI) m/z 747.2 [M + 1]+
2037[Figure (not displayed)]
MS (ESI) m/z 615.1 [M + 1]+
Example 3
Compounds in Table 3 can be synthesized using methods described in Example 3. Many of the reactions described in Examples 1 and 2 were also used to synthesize compounds in Table 3.
[Figure (not displayed)]
3-amino-6-chloropicolinamide (1, 3.00 g, 16.6 mmol) is dissolved in 1,1,1-triethoxyethane (45 mL, 16.6 mmol) in a flame dried round bottom flask equipped with a stir bar. The reaction mixture heated to 110° C. for 90 min then cooled to 10° C. and diluted with cold ether. The solids are filtered and washed several times with cold ether. Drying the solids in vacuo afforded 6-chloro-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one (2).
6-chloro-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one (2, 1.00 g, 5.1 mmol) is dissolved in DMSO (30 mL) in a round bottomed flask equipped with a stir bar. The reaction mixture is stirred at 10° C. while bis(trifluoromethylsulfonyl)zinc (4.23 g, 12.8 mmol) is added in 1 portion. tert-Butyl hydroperoxide (3.53 mL, 19.2 mmol) is then added dropwise via addition funnel. After 5 min the reaction mixture is warmed to room temperature and after an additional 5 min it is warmed to 50° C. for 6.5 h. The reaction mixture is cooled to room temperature and then the reaction mixture is diluted with saturated sodium bicarbonate and ethyl acetate. The layers are separated and the aqueous phase extracted with ethyl acetate three times. The combined organic material is washed with brine and dried over magnesium sulfate. The solids are filtered and solvent removed in vacuo to afford 6-chloro-2-methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (3).
[Figure (not displayed)]
A solution of 6-bromo-2-methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (1, 0.3 g, 0.977 mmol), sodium thiomethoxide (0.102 g, 1.46 mmol), N,N-diisopropylethylamine (0.378 g, 2.93 mmol), and Xantphos (0.056 g, 0.097 mmol) in toluene (3 mL) is degassed for 10 min using argon. Then, tris(dibenzylideneacetone)dipalladium(0) (0.042 g, 0.048 mmol) is added and the mixture is degassed again with argon for 5 min. The reaction mixture is stirred at 90° C. for 2 h. After this time, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain the crude product. This is purified by flash column chromatography using silica gel (100-200 mesh) and 60-80% ethyl acetate in hexanes as eluent to afford 2-methyl-6-(methylthio)-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (2).
To a solution of 2-methyl-6-(methylthio)-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (2, 0.2 g, 0.727 mmol) in ethyl acetate (4.0 mL) and water (1.0 mL) is added ruthenium(III) chloride (0.007 g, 0.0363 mmol) followed by sodium periodate (0.929 g, 4.36 mmol). The reaction mixture is stirred at room temperature for 30 min. After this time, the reaction mixture is filtered and the filtrate is concentrated under reduced pressure to obtain the crude product. This is purified by pentane wash to afford 2-methyl-6-(methylsulfonyl)-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (3).
[Figure (not displayed)]
6-chloro-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one (1, 1.00 g, 5.1 mmol) is dissolved in dimethyl sulfoxide (30 mL) in a round bottomed flask equipped with a stir bar. The reaction mixture is stirred at 10° C. while bis(trifluoromethylsulfonyl)zinc (4.23 g, 12.8 mmol) is added in 1 portion. tert-Butyl hydroperoxide (3.53 mL, 19.2 mmol) is then added dropwise via addition funnel. After 5 min the reaction mixture is warmed to room temperature and after an additional 5 min it is warmed to 50° C. for 6.5 h. The reaction mixture is cooled to room temperature and then diluted with saturated aqueous sodium bicarbonate and ethyl acetate. The layers are separated and the aqueous phase extracted with ethyl acetate three times. The combined organic material is washed with brine and dried over magnesium sulfate. The solids are filtered and solvent removed in vacuo to afford a mixture of 6-chloro-2-methyl-8-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one (2).
[Figure (not displayed)]
5-bromo-6-chloro-3-(4-methoxybenzyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (1, 50 mg, 0.13 mmol) and copper(I) iodide (26.5 mg, 0.139 mmol) are combined in a sealable vessel with a stirbar and suspended in 1 mL 2-(dimethylamino)ethan-1-ol (1a). The resulting mixture is sparged with argon for 3 min and then sealed, vigorously stirred, and heated at 100° C. After 10 min LCMS shows complete consumption of the starting material. The mixture is cooled to room temperature and concentrated. The residue is taken up in MeCN/DMSO and purified by prep-HPLC (MeCN/water+0.1% TFA) to afford 6-chloro-5-(2-(dimethylamino)ethoxy)-3-(4-methoxybenzyl)-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one (2).
[Figure (not displayed)]
To a solution of 3-bromo-2-chloroisonicotinic acid (1, 3.0 g, 12.76 mmol) in dichloromethane (20 mL) is added N,N-dimethylformamide (0.09 mL, 1.27 mmol) at 0° C. followed by oxalyl chloride (1.7 mL, 19.14 mmol). Then the reaction mixture is stirred at −25° C. for 2 h. After completion, the reaction mixture is evaporated to dryness under reduced pressure. Crude reaction mixture is diluted with dichloromethane (10 mL) and poured into ice cold aqueous ammonia in a drop wise manner. Precipitated solid is filtered through sintered funnel and dried under vacuum to afford 3-bromo-2-chloroisonicotinamide (2).
To a solution of 3-bromo-2-chloroisonicotinamide (2, 2.5 g, 10.68 mmol), pentamethylcyclopentadienylrhodium(III) chloride dimer (0.33 g, 0.53 mmol) and cesium acetate (1.02 g, 5.34 mmol) in 1,2-dichloroethane (25 mL) is added tert-butyl 2-diazo-3-oxobutanoate (2b, 2.96 g, 16.00 mmol) to the reaction mixture at room temperature under nitrogen atmosphere. Reaction mixture is heated to 100° C. for 16 h. After completion, the reaction mixture is cooled to room temperature, concentrated to dryness under reduced pressure followed by washing with ether and pentane to afford tert-butyl 8-bromo-7-chloro-3-methyl-1-oxo-1,2-dihydro-2,6-naphthyridine-4-carboxylate (3).
To tert-butyl 8-bromo-7-chloro-3-methyl-1-oxo-1,2-dihydro-2,6-naphthyridine-4-carboxylate (3, 3.0 g, 8.00 mmol) 30% hydrobromic acid in acetic acid (30 mL) is added and the reaction mixture is stirred at 80° C. for 16 h. After completion, the reaction is quenched with ice cold water and extracted with ethyl acetate. The organic layer is washed with cold water, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to afford crude 8-bromo-7-chloro-3-methyl-2,6-naphthyridin-1(2H)-one (4).
[Figure (not displayed)]
4-Amino-6-methylnicotinic acid (1, 700 mg, 4.6 mmol) and ammonium acetate (1.58 g, 20.6 mmol) are dissolved in 1,4-dioxane (8 mL) and acetic anhydride (1a, 1.74 mL, 18.4 mmol) in an oven-dried microwave vial equipped with a stir bar. The reaction mixture is stirred at 200° C. in a microwave reactor for 24 h. Solvent is removed in vacuo. Ethyl acetate is added and the precipitate is filtered and washed once with ethyl acetate. Solids are dried under vacuum to afford 2,7-dimethylpyrido[4,3-d]pyrimidin-4(3H)-one (2).
2,7-Dimethylpyrido[4,3-d]pyrimidin-4(3H)-one (2, 92 mg, 0.50 mmol) and 1-(chloromethyl)-4-methoxybenzene (2a, 0.08 mL, 0.60 mmol) are dissolved in N,N dimethylformamide (2.5 mL) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at room temperature while potassium carbonate (137.9 mg, 1 mmol) and potassium iodide (16.5 mg, 0.10 mmol) are added sequentially. After 20 h the reaction mixture is diluted with ethyl acetate and then washed with a 50:50 water:brine solution and then twice more with 100% brine. The organic material is then dried over magnesium sulfate, filtered and solvent removed in vacuo. Purification via silica gel chromatography (25-100% ethyl acetate in hexanes) afforded the 3-(4-methoxybenzyl)-2,7-dimethylpyrido[4,3-d]pyrimidin-4(3H)-one (3).
3-(4-Methoxybenzyl)-2,7-dimethylpyrido[4,3-d]pyrimidin-4(3H)-one (3, 109 mg, 0.37 mmol) is dissolved in dichloromethane (2 mL) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at 0° C. while is 3-chlorobenzenecarboperoxoic acid (84 mg, 0.49 mmol) added slowly. After 5 min the reaction mixture is warmed to room temperature. After 3 h the reaction mixture is diluted with saturated aqueous sodium bicarbonate and dichloromethane. The layers are separated and the aqueous phase extracted with dichloromethane once. The combined organic material is washed with brine and dried over magnesium sulfate. The solids are filtered and solvent removed in vacuo to afford 3-(4-methoxybenzyl)-2,7-dimethyl-4-oxo-3,4-dihydropyrido[4,3-d]pyrimidine 6-oxide (4).
3-(4-Methoxybenzyl)-2,7-dimethyl-4-oxo-3,4-dihydropyrido[4,3-d]pyrimidine 6-oxide (4, 25 mg, 0.06 mmol) is dissolved in dichloromethane (1 mL) in an oven-dried screw capped vial equipped with a stir bar. The reaction mixture is stirred at 25° C. and then trimethylsilyl cyanide (0.04 mL, 0.32 mmol) and N,N-dimethylcarbamoyl chloride (0.03 mL, 0.32 mmol) are added sequentially. After 45 min the reaction mixture is warmed to 45° C. After 14 h the reaction mixture is cooled to room temperature and solvent is removed in vacuo. Purification via silica gel chromatography (25-80% ethyl acetate in dichloromethane) afforded 3-(4-methoxybenzyl)-2,7-dimethyl-4-oxo-3,4-dihydropyrido[4,3-d]pyrimidine-5-carbonitrile (5).
[Figure (not displayed)]
A solution of 5-chloro-6-(trifluoromethyl)pyridin-2-amine (1, 100 mg, 0.51 mmol) and N-Bromosuccinimide (91 mg, 0.51 mmol) in MeCN (4 mL) heated at 80° C. for 1 hr. After this time, the reaction mixture is concentrated, diluted with water and extracted with ethyl acetate. The combined organic layer is washed with water and brine solution, dried over sodium sulfate and concentrated. The crude material then directly loaded on an Isco loading column. Purified by column chromatography using 5 to 40% ethyl acetate in hexane as eluent and product eluted around 20% ethylacetate/hexane. The desired fractions are concentrated under reduced pressure to afford 3-bromo-5-chloro-6-(trifluoromethyl)pyridin-2-amine (2).
A solution of 3-bromo-5-chloro-6-(trifluoromethyl)pyridin-2-amine (2, 50 mg, 0.18 mmol) and dicyanozinc (24 mg, 0.19 mmol) in NMP (3 mL) is purged with argon-gas for 5-min, then Pd(PPh3)4 (21 mg, 0.018 mmol) is added. The mixture is heated at 120° C. for 30 min in microwave. After completion, the reaction mixture is directly loaded on the silica column. Purified by column chromatography using 0 to 20% methanol in dichloromethane as eluent and product eluted around 10% methanol/dicholomethane. The desired fractions are concentrated under reduced pressure to afford 2-amino-5-chloro-6-(trifluoromethyl)nicotinonitrile (3).
2-amino-5-chloro-6-(trifluoromethyl)nicotinonitrile (3, 550 mg, 2.5 mmol) is dissolved in concentrated sulfuric acid (1 mL) in a round bottom flask, and the mixture is stirred at 90° C. for 15 min. After this time, the reaction stopped and the mixture is cooled to room temperature. The reaction mixture is poured into ice-water and adjusted to pH 8 with saturated sodium hydrogen carbonate solution. The precipitate is collected by filtration and washed with cold water and dried in high vacuum to afford 2-amino-5-chloro-6-(trifluoromethyl)nicotinamide (4).
A solution of 2-amino-5-chloro-6-(trifluoromethyl)nicotinamide (4, 65 mg, 0.27 mmol), 1,1,1-triethoxyethane (0.13 mL, 1.09 mmol) and ethanol (2 mL) in a vial is heated to 120° C. in oil bath for 3 h. After this time, the reaction mixture is diluted with 50% DMSO/MeOH, filtered and the crude is purified by HPLC (C18, prep column, 5-35% MeCN/water+0.1% TFA) to afford 6-chloro-2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one (5).
[Figure (not displayed)]
A solution of 2,6-dichloro-4-(trifluoromethyl)pyridine (1, 10.0 g, 4.6 mmol), ammonium hydroxide (50 mL) is heated at 180° C. for 4 h. After completion, the reaction mixture is filtered, washed with water & dried to afford 6-chloro-4-(trifluoromethyl)pyridin-2-amine (2).
To a mixture of 6-chloro-4-(trifluoromethyl)pyridin-2-amine (2, 2.2 g, 1.0 mmol) in phosphorous oxychloride (5 mL), 3-acetyldihydrofuran-2(3H)-one (2a, 0.256 g, 2.0 mmol) is added at room temperature followed by heating and stirring at 20° C. for 1.5 h. After completion, the reaction mixture is poured into crushed ice & extracted with ethyl acetate. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure to afford 6-chloro-3-(2-chloroethyl)-2-methyl-8-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (3).
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To a solution of 3-methyl-1-oxo-6-(trifluoromethyl)-1,2-dihydroisoquinoline-8-carbonitrile (6, 0.2 g, 0.793 mmol) in acetonitrile (2 mL), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) or selectfluor (0.42 g, 1.190 mmol) and catalytic amount of acetic acid are added and the reaction mixture is stirred at 60° C. for 8 h. After completion, the reaction mixture is quenched with water and extracted with ethyl acetate. The organic layer is washed with brine solution, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude is purified by column chromatography using silica gel (100-200 mesh) and 0-40% ethyl acetate in hexane as eluent. The desired fractions are concentrated under reduced pressure to afford 4-fluoro-3-methyl-1-oxo-6-(trifluoromethyl)-1,2-dihydroisoquinoline-8-carbonitrile (7).
[Figure (not displayed)]
A bottle of 1,4-dioxane is sparged with argon gas for 10 min. Methyl 2-bromo-6-chlorobenzoate (1, 257.7 mg, 1.0 mmol), SPhos (37.0 mg, 0.09 mmol), palladium(II) acetate (6.7 mg, 0.03 mmol), potassium carbonate (276.9 mg, 2.0 mmol) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1a, 257.7 mg, 1.0 mmol) are dissolved in 1,4-dioxane (2 mL) and water (0.20 mL) in an oven-dried screw cap vial equipped with a stir bar. The vial is sealed and the reaction mixture sparged with argon gas for 5 min. The reaction mixture is stirred vigorously at 100° C. for 13 h. The reaction mixture is then cooled to room temperature and diluted with water (20 mL). The solids are filtered to afford a thick yellow semisolid that is taken up in dichloromethane (20 mL) and filtered again. The white solids that remained are collected and dried, affording 7-chlorophenanthridin-6(5H)-one (2).
[Figure (not displayed)]
To a stirred solution of 3,5-bis(trifluoromethyl)aniline (1, 10 g, 43.64 mmol) and 402f (1a, 8.66 g, 52.37 mmol) in water (90 mL) is added hydroxyl amine hydrochloride (10.91 g, 157.11 mmol), followed by sodium sulphate (13.63 g, 96.01 mmol) at room temperature and the mixture is stirred at same temperature for 10 min. Concentrated hydrochloric acid (10.0 mL) is added slowly. The reaction mixture is heated to reflux for 16 h and allowed to cool to room temperature. The solid precipitate formed is filtered and washed with diethyl ether and dried under vacuum to afford (E)-N-(3,5-bis(trifluoromethyl)phenyl)-2-(hydroxyimino)acetamide (2).
A solution of (E)-N-(3,5-bis(trifluoromethyl)phenyl)-2-(hydroxyimino)acetamide (2, 8.0 g, 26.65 mmol) in concentrated sulfuric acid (60.0 mL) is heated to 85° C. and stirred for 4 h. After completion, the reaction is quenched with ice cold water. Solid is obtained, filtered, washed with water and dry under vacuum to afford 4, 6-bis (trifluoromethyl) indoline-2, 3-dione (3).
To a stirred solution of 4, 6-bis (trifluoromethyl) indoline-2, 3-dione (3, 6.5 g, 22.96 mmol) in 1 N sodium hydroxide solution (120.0 mL) is added hydrogen peroxide solution (30% in water, 9.10 mL, 80.36 mmol) drop wise at 0° C. The reaction is allowed to warm up to room temperature and stirred for 4 h. After completion, the reaction mixture is quenched with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to afford 2-amino-4,6-bis(trifluoromethyl)benzoic acid (4).
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To a solution of 7-chloro-6-fluoro-2-methyl-4-oxo-3,4-dihydroquinazoline-5-carbonitrile (5, 0.280 g, 1.17 mmol) in ethanol (3 mL), methylhydrazine (7, 0.33 mL, 5.85 mmol) is added. This mixture is heated at 100° C. for 16 h. The reaction mixture is cooled and the resulting precipitate is collected by filtration and dried to afford 1-amino-4-chloro-3,7-dimethyl-3,8-dihydro-9H-pyrazolo[4,3-f]quinazolin-9-one (6).
To a solution of 1-amino-4-chloro-3,7-dimethyl-3,8-dihydro-9H-pyrazolo[4,3-f]quinazolin-9-one (6, 0.100 g, 0.37 mmol) in tetrahydrofuran (2 mL), tert-butyl nitrite (0.14 mL, 1.1 mmol) is added. This mixture is heated at 70° C. for 16 h. The reaction mixture is cooled, diluted with water, and extracted with 10% methanol in dichloromethane. The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by silica gel (100-200 mesh) column chromatography using 0-70% ethyl acetate in hexanes as eluent to afford 4-chloro-3,7-dimethyl-3,8-dihydro-9H-pyrazolo[4,3-f]quinazolin-9-one (7).
[Figure (not displayed)]
p-Toluenesulfonic acid monohydrate (74.7 mg, 0.39 mmol) is added to a stirred solution of 5-benzyloxypentan-2-one (5, 3.02 g, 15.7 mmol) in methanol (15 mL) and trimethyl orthoformate (3.44 mL, 31.4 mmol) at room temperature under a reflux condenser under argon. The resulting reaction mixture is heated at 50° C. under a reflux condenser under argon for 1.5 h. After cooling to room temperature, sodium methoxide (25 wt. % in methanol) (0.18 mL, 0.78 mmol) is added and then most of the solvent is removed on a rotary evaporator. The residue is partitioned between ethyl acetate and brine with a little 0.1 N NaOH in it. The organics are washed with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and dried under high vacuum to afford crude (((4,4-dimethoxypentyl)oxy)methyl)benzene (6).
2-Bromo-6-(methylamino)-4-(trifluoromethyl)benzamide (4, 1.11 g, 3.7 mmol), (((4,4-dimethoxypentyl)oxy)methyl)benzene (6, 1.33 g, 5.6 mmol), p-toluenesulfonic acid monohydrate (35.5 mg, 0.19 mmol) and toluene (20 mL) are combined in a 100 mL round bottom flask with a stirbar, stirred vigorously, and heated at 100° C. under argon for 40 min. Most of the volatiles are removed on a rotary evaporator. The residue is purified via silica gel chromatography (10-80% ethyl acetate in hexanes) to afford 2-(3-(benzyloxy)propyl)-5-bromo-1,2-dimethyl-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-one (7).
2-(3-(benzyloxy)propyl)-5-bromo-1,2-dimethyl-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-one (7, 1.64 g, 3.48 mmol), acetic anhydride (11.1 mL, 118 mmol), and pyridine (1.12 mL, 13.9 mmol) are combined in a sealable vessel with a stirbar, sealed, stirred, and heated at 110° C. with a block heater for 16 h. Most of the volatiles are removed on a rotary evaporator. The residue is taken up in ethyl acetate and purified via silica gel chromatography (30-90% ethyl acetate in hexanes) to afford 2-(3-(benzyloxy)propyl)-5-bromo-1-methyl-7-(trifluoromethyl)quinolin-4(1H)-one (8) and 3-(2-(benzyloxy)ethyl)-5-bromo-1,2-dimethyl-7-(trifluoromethyl)quinolin-4(1H)-one (9).
[Figure (not displayed)]
To a solution of 4-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzene-1,2-diamine (3, 12.0 g, 43.7 mmol) in ethanol (120 mL) at 0° C. is added ethyl pyruvate (10.0 g, 87.5 mmol) and the reaction mixture is stirred for 3 h at room temperature. After completion, the reaction mixture is cooled to 0° C., filtered and washed with diethyl ether which is dried under reduced pressure to afford 3-methyl-7-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)quinoxalin-2(1H)-one (4).
To a solution of 3-methyl-7-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)quinoxalin-2(1H)-one (4, 4.3 g, 13.1 mmol) is added phosphoryl chloride (43 mL) at room temperature. Then the reaction mixture is stirred for 6 h at 90° C. After completion, the reaction mixture is quenched with icec-cold water, adjusted the pH 8 with 1 N aqueous hydrochloric acid solution and extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to get the crude mass. The crude compound is purified by Combi flash (12 g, Redi Sep column) using 4% methanol in dichloromethane as eluent. The desired fractions are concentrated under reduced pressure to afford 2-chloro-3-methyl-7-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)quinoxaline (5).
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To 4-benzyloxy-1-[2-fluoro-6-prop-1-ynyl-4-(trifluoromethyl)phenyl]butan-1-one (1, 50 mg, 0.13200 mmol) in 1,4-Dioxane (1 mL) and water (0.01 mL, 0.79000 mmol) is added dichloroplatinum (3.52 mg, 0.01320 mmol) and CO (29.6 mg, 1.06 mmol) is bubbled through the reaction mixture for 5 mins. The mixture is stirred at 25° C. for 30 min followed by heating to 100 for 12 hr to afford 2-(2-(benzyloxy)ethyl)-8-fluoro-3-methyl-6-(trifluoromethyl)naphthalen-1-ol (2) after workup.
[Figure (not displayed)]
A mixture of 2-amino-6-bromo-3-fluorobenzoic acid (2.00 g, 8.55 mmol) and urea (4.00 g, 66.60 mmol) is heated at 180° C. for 3 h, then cooled to 80° C. Water (7-10 mL) is added. The reaction is stirred at reflux for 10 m. The resulting mixture is cooled to room temperature and filtered. The dark brown solid is washed with water and ethyl ether, and dried under vacuum to afford 5-bromo-8-fluoroquinazoline-2,4(1H,3H)-dione (2).
To a solution of 5-bromo-8-fluoroquinazoline-2,4(1H,3H)-dione (2, 445 mg, 1.72 mmol) in phosphorus oxychloride (6.2 mL) is added N,N-diisopropylethylamine (1.20 mL, 6.89 mmol) dropwise. The reaction is stirred at 120° C. overnight. The resulting mixture is cooled to room temperature and azeptroped with toluene. The crude is diluted with ethyl acetate and washed with water. The combined organics are dried over sodium sulfate, decanted and concentrated. The crude is purified via column chromatography (silica, ethyl acetate/hexanes=0-10%) to afford 5-bromo-2,4-dichloro-8-fluoroquinazoline (3).
To a solution of 5-bromo-2,4-dichloro-8-fluoroquinazoline (3, 395 mg, 1.33 mmol) in tetrahydrofuran (2 mL) is added 1 M sodium hydroxide solution (6.70 mL, 6.70 mmol). The reaction is stirred at room temperature for 1 h 45 min. The resulting mixture is acidified to ˜pH 4 with acetic acid. The precipitate is filtered, washed with ethyl ether and dried under vacuum to afford 5-bromo-2-chloro-8-fluoroquinazolin-4(3H)-one (4).
To a solution of 5-bromo-2-chloro-8-fluoroquinazolin-4(3H)-one (4, 100 mg, 0.36 mmol) in N,N-dimethylformamide (2 mL) is added 1-(4-methoxyphenyl)-N-methylmethanamine (68 uL, 0.45 mmol). The reaction is microwaved at 120° C. for 10 m. The resulting mixture is cooled to room temperature and sit for 90 min. The precipitate is filtered and washed with ethyl ether. The filtrate is concentrated and triturated with ethyl acetate. The combined solids are dried under vacuum to afford 5-bromo-8-fluoro-2-((4-methoxybenzyl)(methyl)amino)quinazolin-4(3H)-one (5).
[Figure (not displayed)]
To a solution of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (1, 25.0 g, 132.9 mmol) in tetrahydrofuran (250 mL), N-iodosuccinimide (35.89 g, 159.5 mmol) is added portion wise over a period of 10 min and the reaction mixture is allowed to stir at room temperature for 30 h. After completion, the reaction mixture is quenched with water and extracted with ethyl acetate. The organic layer is washed with water, separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford 2,4-dichloro-7-iodo-5H-pyrrolo[3,2-d]pyrimidine (2).
To a solution of 2,4-dichloro-7-iodo-5H-pyrrolo[3,2-d]pyrimidine (2, 30.0 g, 95.5 mmol) in methanol (600 mL), potassium carbonate (39.62 g, 286.7 mmol) is added portion wise over a period of 10 min and the reaction mixture is allowed to stir at 80° C. for 24 h. After completion, the reaction mixture is concentrated, diluted with water and extracted with ethyl acetate. The organic layer is washed with water, separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude. The crude is triturated with diethyl ether to afford 2-chloro-7-iodo-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine (3).
To a solution of 2-chloro-7-iodo-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine (3, 24.0 g, 77.54 mmol) in N,N-dimethylformamide (240 mL), zinc cyanide (9.11 g, 77.54 mmol), zinc acetate (14.22 g, 77.54 mmol) and zinc dust (2.02 g, 31.01 mmol) are added at room temperature. The reaction mixture is degassed with argon for 15 min. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) (5.67 g, 7.75 mmol) and palladium acetate (0.87 g, 3.87 mmol) are added and mixture is heated at 80° C. for 1 h. After completion, the reaction mass is diluted with ethyl acetate and washed with cold water. The organic layer is separated, dried over anhydrous sodium sulphate, filtered and concentrated to get crude. The crude is purified by column chromatography over silica gel (100-200 mesh) using 0-50% ethyl acetate in hexanes as eluent. The desired fractions are concentrated in vacuo to afford 2-chloro-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile (4).
To a solution of 2-chloro-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile (4, 10.0 g, 47.9 mmol) in isopropanol (100 mL), aniline (5, 43.76 mL, 479.3 mmol) and p-toluene sulfonic acid monohydrate (10.93 g, 57.48 mmol) are added. The reaction mixture is allowed to stir at 80° C. for 16 h. After completion, the reaction mixture is quenched with water and extracted with ethyl acetate. The organic layer is washed with water, brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude. The crude is triturated with n-pentane, diethyl ether and dried under high vacuo to afford 4-methoxy-2-(phenylamino)-5H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile (6).
[Figure (not displayed)]
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A solution of 4-bromo-1-chloro-2-fluorobenzene (1, 20.0 g, 95.69 mmol) in tetrahydrofuran (200 mL) is cooled at −78° C., then lithium di-isopropyl amide (2 M in tetrahydrofuran) (57.2 mL, 114.83 mmol) is added dropwise to the mixture and reaction mixture is stirred at −78° C. for 1 h. Then, N,N-dimethylformamide (20.0 mL) is added drop wise for 15 min at −78° C. and reaction mixture is stirred for 30 min. After completion reaction mixture is quenched with ammonium chloride solution, diluted with water, and extracted with diethyl ether. The organic layer is dried over anhydrous sodium sulphate, filtered and concentrated to get crude compound. Crude compound obtained is washed with pentane to afford 6-bromo-3-chloro-2-fluorobenzaldehyde (2).
To a solution of 6-bromo-3-chloro-2-fluorobenzaldehyde (2, 18.0 g, 75.94 mmol), in acetonitrile (180.0 mL) and dimethylsulphoxide (48.0 mL), triethyl amine (31.96 mL, 227.84 mmol) is added at 0° C. followed by ethyl 2-mercaptoacetate (2a, 18.2 g, 151.89 mmol) and continued stirring at 50° C. for 4 h. After completion, reaction mixture is diluted with water and extracted with ethyl acetate, washed with 1 N hydrochloric acid, water and brine solution. Organic layer is dried over sodium sulfate and concentrated to dryness under reduced pressure. Triturated with ethanol, filtered and dried to afford ethyl 4-bromo-7-chlorobenzo[b]thiophene-2-carboxylate (3).
To a solution of ethyl ethyl 4-bromo-7-chlorobenzo[b]thiophene-2-carboxylate (3, 18.0 g, 56.42 mmol) and in tetrahydrofuran:water:methanol (90.0 mL: 45 mL: 45 mL), lithium hydroxide (13.54 g, 564.26 mmol) is added, and the reaction mixture is continued stirring for 2 h. After completion, reaction mixture is poured on chilled 1 N aqueous hydrochloric acid, and extracted with ethyl acetate, washed with water and brine solution. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. Triturated with ether, filtered and dried to afford 4-bromo-7-chlorobenzo[b]thiophene-2-carboxylic acid (4).
To a solution of 4-bromo-7-chlorobenzo[b]thiophene-2-carboxylic acid (4, 15.0 g, 51.90 mmol), in N,N-dimethyl acetamide (150.0 mL), 1, 8-diazabicyclo (5.4.0) undec-7-ene (39.55 g, 259.51 mmol) is added and mixture is heated at 180° C. for 4 h. After completion, reaction mixture is cooled to room temperature diluted with water and acidified by 1 N hydrochloric acid and extracted with ethyl acetate, washed with, water and brine solution. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure to afford 4-bromo-7-chlorobenzo[b]thiophene (5).
To a solution of 4-bromo-7-chlorobenzo[b]thiophene (5, 4.00 g, 16.19 mmol) in dichloromethane (100.0 mL), dichloro(methoxy)methane (5a, 4.59 g, 24.29 mmol) is added at 0° C. followed by titanium tetrachloride (2.79 g, 24.29 mmol) at same temperature and the reaction mixture is continued stirring for 16 h at room temperature. After completion, reaction mixture is quenched with 1 N aqueous hydrochloric acid and continued stirring for 2 h, diluted with water and extracted with dichloromethane, washed with water and brine solution. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The crude product is purified by flash chromatography using silica (100-200 mesh) using 0-10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 4-bromo-7-chlorobenzo[b]thiophene-3-carbaldehyde (6).
To a solution of 4-bromo-7-chlorobenzo[b]thiophene-3-carbaldehyde (6, 2.50 g, 9.12 mmol) in 1,4-dioxane (24.0 mL) and water (8.0 mL), (3:1 ratio) is added sodium chlorite (1.24 g, 13.68 mmol), followed by sulfamic acid (5.30 g, 54.74 mmol) at room temperature and the mixture is continued stirring for 16 h. After completion, reaction mixture is concentrated under reduced pressure; residue is acidified to pH-2 by 2 N hydrochloric acid and extracted with ethyl acetate, washed with water and brine solution. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue is triturated with n-pentane, filtered and dried to afford 4-bromo-7-chlorobenzo[b]thiophene-3-carboxylic acid (7).
To a solution of 4-bromo-7-chlorobenzo[b]thiophene-3-carboxylic acid (7, 1.40 g, 4.81 mmol) in t-butanol (15.0 mL), di-tert-butyl dicarbonate (2.0 g, 9.62 mmol) followed by dimethylaminopyridine (0.586 g, 4.81 mmol) is added at room temperature. The solution is heated at 90° C. and continued stirring for 16 h. After completion, reaction mixture is concentrated under reduced pressure; diluted with water and extracted with ethyl acetate, washed with water and brine solution. Organic layer is dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude is purified by flash chromatography using silica (100-200 mesh) by eluting with gradient of 5-10% ethyl acetate in hexanes. The desired fractions are concentrated under reduced pressure to afford tert-butyl 4-bromo-7-chlorobenzo[b]thiophene-3-carboxylate (8).
A solution of tert-butyl 4-bromo-7-chlorobenzo[b]thiophene-3-carboxylate (8, 1.10 g, 3.17 mmol) and tributyl(vinyl)stannane (1.20 g, 3.80 mmol) in N,N-dimethylformamide (11 mL) is degassed using argon for 15 min. Bis(triphenylphosphine)palladium dichloride (0.222 g, 0.3170 mmol) is added to the reaction mixture and heated at 90° C. for 2 h. The reaction mixture is cooled to room temperature, diluted with ethyl acetate and water. The organic layer is separated, washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get the crude. The crude is purified by column chromatography using silica (100-200 mesh) and 2.0-5.0% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-chloro-4-vinylbenzo[b]thiophene-3-carboxylate (9).
A solution of tert-butyl 7-chloro-4-vinylbenzo[b]thiophene-3-carboxylate (9, 0.6 g, (2.04 mmol) in acetone (10 mL) and water (2 mL) is cooled to 0° C. and osmium tetraoxide (4% solution in water)(1.3 mL, 0.2040 mmol) followed by sodium periodate (1.3 g, 6.12 mmol) is added. The mixture is stirred at room temperature for 1 h. After completion, the reaction mixture is filtered and filtrate is concentrated under reduced pressure to get the crude product. The crude is purified by pentane wash to afford tert-butyl 7-chloro-4-formylbenzo[b]thiophene-3-carboxylate (10).
To a stirred solution of tert-butyl 7-chloro-4-formylbenzo[b]thiophene-3-carboxylate (10, 0.550 g, 1.85 mmol) in dichloromethane (10 mL), diethylaminosulfur trifluoride (0.503 g, 2.77 mmol) is added at 0° C. The reaction is allowed to warm at room temperature and stirred for 4 h. After completion, reaction mixture is concentrated under reduced pressure to get crude. The crude is purified by column chromatography using silica (100-200 mesh) and 5.0-10.0% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford tert-butyl 7-chloro-4-(difluoromethyl)benzo[b]thiophene-3-carboxylate (11).
[Figure (not displayed)]
A solution of 3′-bromo-5-chloro-[1,1′-biphenyl]-2-01 (3, 0.5 g, 1.7 mmol), diisopropyl phosphonate (4, 0.585 g, 3.5 mmol), and triethyl amine (0.533 g, 5.2 mmol) in isopropyl alcohol is degassed with argon for 10 min followed by the addition of bis(diphenylphosphino) ferrocene-palladium(II)dichloride.dichloromethane complex The reaction mixture is stirred at 100° C. for 16 h. After completion, the volatiles are removed under reduced pressure. Crude is purified by flash column chromatography using 30% ethyl acetate hexanes to afford diisopropyl (5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-yl)phosphonate (5).
[Figure (not displayed)]
To a solution of 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxamide (3, 1.50 g, 5.55 mmol) in N,N-dimethylformamide (20 mL), sodium hydride is added at 0° C. and stirred for 10 min. Then, dimethylcarbamic chloride (3a, 0.71 g, 6.66 mmol) is added and the mixture is stirred at room temperature for 2 h. After completion, the reaction mixture is diluted with ethyl acetate, washed with cold water and brine, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is triturated with diethyl ether and pentane and dried to afford 7-bromo-N-(dimethylcarbamoyl)-5-methylthieno[3,2-b]pyridine-3-carboxamide (4).
[Figure (not displayed)]
Methyl 2-hydroxythieno[3,2-b]pyridine-3-carboxylate (1, 748 mg, 3.6 mmol) is dissolved in N,N-dimethylformamide (20 mL) in an oven dried screw cap vial equipped with a stir bar. Potassium carbonate (210 mg, 1.52 mmol) is added, followed by the dropwise addition of 1-(chloromethyl)-4-methoxybenzene (1a, 0.42 mL, 4.2 mmol). The vial is sealed and heated to 75° C. After 22 h additional 4-methoxybenzyl chloride (0.42 mL, 4.2 mmol) and potassium carbonate (946.2 mg, 6.8 mmol) are added and the reaction mixture continued to stir at 75° C. After 3 h the reaction mixture is cooled to room temperature and diluted with ethyl acetate and water. The layers are separated and the aqueous phase is extracted with ethyl acetate twice. The combined organic material is washed with brine, dried over magnesium sulfate, filtered, and solvent removed in vacuo to afford a dark brown oil. Purification via silica gel chromatography, eluting with hexanes and ethyl acetate afforded methyl 2-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine-3-carboxylate (2).
A bottle of tetrahydrofuran is sparged with argon gas for 1 h. An oven dried microwave vial equipped with a stir bar is charged with bis(pinacolato)diboron (308.4 mg, 1.21 mmol), methyl 2-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine-3-carboxylate (2, 381 mg, 1.16 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (2a, 21.8 mg, 0.093 mmol), and (1Z,5Z)-cycloocta-1,5-diene; methoxyiridium (30.6 mg, 0.046 mmol). Tetrahydrofuran (2.3 mL) is added, the vial is sealed and placed under an atmosphere of argon before being stirred in an oil bath at 80° C. After 16 h the reaction mixture is cooled to room temperature and solvent removed in vacuo. The crude residue is used without further purification for the subsequent reaction. Methyl 2-((4-methoxybenzyl)oxy)-7-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)thieno[3,2-b]pyridine-3-carboxylate (3).
[Figure (not displayed)]
To a solution of 3-(benzylthio)-7-chloro-5-methylthieno[3,2-b]pyridine (1, 0.7 g, 2.3 mmol) in a mixture of acetonitrile, acetic acid and water (40:2:1) (10.0 mL) at 0° C. 1,3-Dichloro-5,5-dimethylimidazolidine-2,4-dione (1a, 0.9 g, 4.60 mmol) at 0° C. and the mixture is stirred for 1 h. Ammonium hydroxide (35% in water, 6.0 mL) is added is added to the reaction mixture at 0° C. and stirring is continued for 2 h. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is washed with n-pentanes to afford 7-chloro-5-methylthieno[3,2-b]pyridine-3-sulfonamide (2).
To a solution of methyl 7-chloro-5-methylthieno[3,2-b]pyridine-3-sulfonamide (2, 0.50 g, 1.9 mmol) in acetic anhydride (6.0 mL) is added zinc chloride (0.08 g, 0.57 mmol) at room temperature and the mixture is heated and stirred for 16 h at 75° C. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified by washing with diethyl ether and n-pentanes to afford N-((7-chloro-5-methylthieno[3,2-b]pyridin-3-yl)sulfonyl)acetamide (3).
[Figure (not displayed)]
A solution of 5-(1-((4-bromothiophen-3-yl)amino)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (1, 0.250 g, 0.722 mmol) in N-methyl pyrrolidone (2 mL) is heated in microwave at 200° C. for 30 min. After completion, the reaction mixture is diluted with dichloromethane and then silica gel is added. The solvent is then evaporated and the free flow silica gel is then loaded on the Isco column and purified via silica gel chromatography eluting with methanol/ethylacetate. The desired fractions are concentrated under reduced pressure to afford 3-bromo-5-methylthieno[3,2-b]pyridin-7-ol (2).
To a solution of 3-bromo-5-methylthieno[3,2-b]pyridin-7-ol (2, 177 mg, 0.725 mmol), phenylmethanethiol (2a, 0.361 g, 2.91 mmol) and N,N-diisopropylethylamine (0.379 mL, 2.15 mmol) in monoglyme (4 mL) is added premixed solution of tris(dibenzylideneacetone)dipalladium(0) (132 mg, 0.145 mmol) and (R)-1-[(Sp)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (80 mg, 0.145 mmol) in monoglyme (1 mL) at room temperature. The reaction mixture is purged with argon gas for 5 min, and the mixture is heated at 110° C. for 15 h. After completion, the reaction mixture is diluted with dichloromethane and then silica gel is added. The solvent is then evaporated and the free flow silica gel is then loaded on the Isco column and purified via silica gel chromatography eluting with Ethylacetate/hexanes. The desired fractions are concentrated under reduced pressure to afford 3-(benzylthio)-5-methylthieno[3,2-b]pyridin-7-ol (3).
To a solution of 3-(benzylthio)-5-methylthieno[3,2-b]pyridin-7-ol (3, 0.100 g, 0.347 mmol) in 1,2-dichloroethane (3.0 mL), phosphoryl trichloride (0.1 mL, 1.04 mmol) and catalytic amount of N,N-dimethylformamide (0.050 mL) are added at room temperature. The reaction mixture is heated at 90° C. for 2 h. After completion, the reaction mixture is diluted with dichloromethane and then silica gel is added. The solvent is then evaporated and the free flow silica gel is then loaded on the Isco column and purified via silica gel chromatography eluting with methanol/dichloromethane to afford 3-(benzylthio)-7-chloro-5-methylthieno[3,2-b]pyridine (4).
A solution of 3-(benzylthio)-7-chloro-5-methylthieno[3,2-b]pyridine (4, 50 mg, 0.163 mmol) and 1,3-dichloro-5,5-dimethyl-imidazolidine-2,4-dione (4a, 64 mg, 0.329 mmol) in mixture of acetonitrile (3 mL)/water (2 mL)/acetic acid (0.4 mL) is stirred at room temperature for 1 h. To this mixture is then added hydroxyl(trimethylstannane) (295 mg, 1.63 mmol) and then stirred for 15 h at 50° C. The reaction mixture is then concentrated to afford crude 7-chloro-5-methylthieno[3,2-b]pyridine-3-sulfonic acid (5).
[Figure (not displayed)]
To a solution of methyl 7-bromo-5-methylthieno[3,2-b]pyridine-3-carboxylate (1, 3.00 g, 10.4 mmol) in dichloromethane (30.0 mL) at −78° C., diisobutylaluminium hydride (10.40 mL, 15.7 mmol) is added. The reaction mixture is stirred this temperature for 3 h. After this time, the reaction mixture is diluted with water and extracted with dichloromethane. The organic layer is washed with water and then brine, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to afford (7-bromo-5-methylthieno[3,2-b]pyridin-3-yl)methanol (2).
To a solution of (7-bromo-5-methylthieno[3,2-b]pyridin-3-yl)methanol (2, 1.70 g, 3.87 mmol) in dichloromethane (20.0 mL) at 0° C., 1,1,1-tris(acetyloxy)-1,1-dihyro-1,2-benziodoxol-3-(1H)-one (3.28 g, 7.75 mmol) is added. The reaction mixture is stirred at room temperature for 3 h. After this time, the reaction mixture is filtered with Celite and washed with dichloromethane. The filtrate is concentrated to dryness under reduced pressure to obtain the crude product. This is purified by silica gel (100-200 mesh) column chromatography using 30-50% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 7-bromo-5-methylthieno[3,2-b]pyridine-3-carbaldehyde (3).
To a solution of 7-bromo-5-methylthieno[3,2-b]pyridine-3-carbaldehyde (3, 0.50 g, 1.95 mmol) in dichloromethane (5.0 mL) at 0° C., trifluoromethyltrimethylsilane (0.416 g, 2.92 mmol) and cesium carbonate (3.17 g 9.75 mmol) is added. The reaction mixture is stirred at room temperature for 1 h. Then, the reaction mixture is diluted with water and extracted with dichloromethane. The organic layer is washed with water and then brine solution, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to afford 7-bromo-5-methyl-3-(2,2,2-trifluoro-1-((trimethylsilyl)oxy)ethyl)thieno[3,2-b]pyridine (4).
[Figure (not displayed)]
To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (1, 20 g, 145.0 mmol) in acetonitrile (80 mL) are added sodium iodide (24 g, 160.0 mmol) and chloramine tetrahydrate (45 g, 160.0 mmol) and stirred at room temperature for 16 h. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product is purified by column chromatography using silica gel (100-200 mesh) and 10% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-fluoro-4-hydroxy-5-iodobenzonitrile (2).
To a solution of 2-fluoro-4-hydroxy-5-iodobenzonitrile (2, 7.0 g, 26.6 mmol) in 1,4-dioxane (70 mL), sodium acetate (4.36 g, 53.23 mmol) and bis pinacolato diboron (20.26 g, 79.8 mmol) are added at room temperature and the mixture is degassed with argon for 10 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (1.9 g, 2.66 mmol), is added to the reaction mixture and degassed for another 15 min. The reaction mixture is heated at 75° C. for 16 h. After completion, the reaction mass is diluted with water and extracted with ethyl acetate. The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 20% ethyl acetate in hexanes as eluent. The desired fractions are concentrated under reduced pressure to afford 2-fluoro-4-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (3).
[Figure (not displayed)]
A solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (1a, 1.048 g, 7.27 mmol) and 1,1,1-triethoxyethane (10.0 mL) is stirred and heated at 90° C. for 2 h in a closed vessel. Methyl 2-aminobenzoate (1, 1 g, 6.62 mmol) is added portion wise at 90° C. under argon atmosphere and continued heating at 90° C. for 6 h. After completion, the reaction mass is cooled to room temperature, added water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated under vacuo to get crude. The crude methyl 2-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)benzoate (2).
A solution of methyl 2-((1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)ethyl)amino)benzoate (2, 0.900 g, 2.82 mmol) in N-methyl pyrrolidone (1 mL) is heated in microwave at 200° C. for 30 min. After completion, the reaction mixture is diluted with dichloromethane and then silica gel is added. The solvent is then evaporated and the free flow silica gel is then loaded on the Isco column and purified via silica gel chromatography eluting with methanol/ethylacetate. The desired fractions are concentrated under reduced pressure to afford methyl 4-hydroxy-2-methylquinoline-8-carboxylate (3).
[Figure (not displayed)]
A solution of methyl 5-formylthiophene-3-carboxylate (1, 2.00 g, 11.7 mmol) and 4-methylbenzenesulfonohydrazide (2.19 g, 11.7 mmol) in 1,4-dioxane (20 mL) is heated at 90° C. for 16 h. The reaction mixture is cooled at room temperature, concentrated under reduced pressure to get the crude. The crude is washed with diethyl ether and dried under vacuum to afford methyl (Z)-5-((2-tosylhydrazineylidene)methyl)thiophene-3-carboxylate (2).
To a solution of methyl (Z)-5-((2-tosylhydrazineylidene)methyl)thiophene-3-carboxylate (2, 0.50 g, 1.47 mmol), (5-chloro-2-hydroxyphenyl)boronic acid (2a, 0.307 g, 1.77 mmol) and potassium carbonate (0.40 g, 2.94 mmol) in 1,4-dioxane:water (4:1, 5 mL) is added and reaction mixture is stirred at 90° C. for 16 h. After completion, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to get crude. The crude is purified by flash column chromatography using silica (100-200 mesh) and 10-20% ethyl acetate in hexanes as eluent to afford methyl 5-(5-chloro-2-hydroxybenzyl)thiophene-3-carboxylate (3).
[Figure (not displayed)]
To a cooled solution of tert-butyl 5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-carboxylate (1, 2.65 g, 8.7 mmol), but-3-yn-1-ol (2, 0.66 mL, 8.7 mmol) and triphenylphosphine (2.28 g, 8.7 mmol) in tetrahydrofuran (14 mL) at 5° C. is added diisopropyl azodicarboxylate (1.71 mL, 8.7 mmol) via syringe over ca. 2 min. This is warmed to room temperature after 15 min and stirred for an additional 18 h. The solvent is removed in vacuo and residue purified via automated flash chromatography, eluting with hexanes and ethyl acetate to afford tert-butyl 2′-(but-3-yn-1-yloxy)-5′-chloro-[1,1′-biphenyl]-3-carboxylate (3).
A flame-dried round bottom flask is charged with ethyl 2,2,2-trifluoroacetate (4, 0.26 mL, 2.18 mmol) and tetrahydrofuran (13 mL). It is cooled to −78° C. and boron trifluoride diethyl etherate (0.29 mL, 2.32 mmol) is added dropwise. After 50 min tert-butyl 2′-(but-3-yn-1-yloxy)-5′-chloro-[1,1′-biphenyl]-3-carboxylate (3, 460 mg, 1.29 mmol) is added slowly followed by slow addition of n-butyllithium solution (2.5 M in hexanes, 0.62 mL, 1.55 mmol). After 1 h the reaction is quenched at −78° C. with the slow addition of saturated aqueous ammonium chloride solution. The solution is warmed to room temperature and ethyl acetate is added. The layers are separated, and the aqueous phase is extracted with ethyl acetate twice. The combined organic material is washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification via automated flash chromatography, eluting with hexanes and ethyl acetate, afforded tert-butyl 5′-chloro-2′-((6,6,6-trifluoro-5-oxohex-3-yn-1-yl)oxy)-[1,1′-biphenyl]-3-carboxylate (5)
[Figure (not displayed)]
Sodium methoxide (25 wt. % in methanol) (3.16 mL, 13.8 mmol) is added to a stirred solution of 3-chloro-2,6-difluoro-pyridine (2a, 2.01 g, 13.4 mmol) in Methanol (5 mL) at 0° C. The cold bath is removed and the resulting cloudy mixture is stirred at room temperature under argon for 35 min. The reaction mixture is poured into water (100 mL). Solids are collected by vacuum filtration, washed thoroughly with water, and air dried using vacuum suction for 30 min. The solids are dried under high vacuum to afford 3-chloro-6-fluoro-2-methoxypyridine (2b).
Potassium carbonate (1.82 g, 13.2 mmol) is added to a stirred solution of 2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (1, 835 mg, 3.30 mmol) and 1,2-dibromoethane (2.84 mL, 33.0 mmol) in DMA (15 mL) at room temperature under argon. The resulting mixture is heated at 60° C. under argon for 3 h. Water (0.59 mL, 33.0 mmol) is added. The resulting mixture is heated at 60° C. under argon for 1 h 15 min. After cooling to room temperature the reaction mixture is partitioned between ethyl acetate and water. The organics are washed three times with brine, dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (20-90% ethyl acetate in hexanes) to afford 3-(2-hydroxyethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (2).
3-(2-Hydroxyethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (2, 390 mg, 1.31 mmol) is dissolved in DMF (4 mL) with stirring under argon. THE (6 mL) is added and the resulting solution is cooled to −78° C. Sodium hydride (34.6 mg, 1.44 mmol) is added and the resulting cloudy mixture is stirred at −78° C. under argon for 10 min. 3-Chloro-6-fluoro-2-methoxypyridine (2b, 254 mg, 1.57 mmol) is added and the cold bath is removed. The resulting mixture is stirred at room temperature under argon for 20 min and then heated at 50° C. under a reflux condenser under argon for 2.5 h. After cooling to room temperature the resulting mixture is partitioned between ethyl acetate and a mixture of brine and saturated aqueous ammonium chloride. The organics are washed twice more with brine, concentrated on a rotary evaporator with silica gel, and purified via silica gel chromatography (0-100% ethyl acetate in hexanes) to afford impure 3-(2-((5-chloro-6-methoxypyridin-2-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (3).
[Figure (not displayed)]
To a solution of tert-butyl 7-(5-chloro-2-hydroxyphenyl)thieno[3,2-b]pyridine-3-carboxylate (3a, 2.0 g, 5.5 mmol) in tetrahydrofuran (15 mL), sodium hydride (0.276 g, 6.9 mmol) is added at 0° C. and the mixture is stirred for 0.5 h. 6-Chloro-3-(2-chloroethyl)-2-methyl-8-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (3, 1.5 g, 4.6 mmol) in tetrahydrofuran is added to the reaction mixture and stirred for 16 h. After completion, the reaction mixture is poured into crushed ice and extracted with ethyl acetate. Organic layer is dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The crude compound obtained is purified through column chromatography using 0-50% ethyl acetate in hexanes as eluent; the fractions containing desired product is distilled off under reduced pressure to afford tert-butyl 7-(5-chloro-2-(2-(6-chloro-2-methyl-4-oxo-8-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (4).
[Figure (not displayed)]
To a mixture of 5-bromo-8-fluoro-2-((4-methoxybenzyl)(methyl)amino)quinazolin-4(3H)-one (5, 95 mg, 0.23 mmol), tert-butyl 2′-(2-bromoethoxy)-5′-chloro-[1,1′-biphenyl]-3-carboxylate (5a, 99 mg, 0.24 mmol), nickel(II) iodide hydrate (30 mg, 0.08 mmol), sodium iodide (17 mg, 0.12 mmol), p-tolunitrile (11 mg, 0.09 mmol), 4,4′-dimethoxy-2,2′-bipyridine (20 mg, 0.09 mmol) in freshly sparged N,N-dimethylacetamide (1.2 mL) are added chlorotrimethylsilane (1 drop), pyridine (1 drop) and manganese (25 mg, 0.46 mmol). The reaction is stirred at 80° C. overnight. The resulting mixture is cooled to room temperature and filtered through a pad of Celite. The filtrate is extracted with ethyl acetate and water. The combined organics are dried over sodium sulfate, decanted and concentrated. The crude is purified via column chromatography (silica, ethyl acetate/hexanes=0-40%) to afford 5′-chloro-2′-(2-(8-fluoro-2-((4-methoxybenzyl)(methyl)amino)-4-oxo-3,4-dihydroquinazolin-5-yl)ethoxy)-[1,1′-biphenyl]-3-carboxylic acid (6).
[Figure (not displayed)]
6-Amino-2-(phenylamino)pyrimidin-4-ol (6, 114 mg, 0.45 mmol) is dissolved in dimethylsulfoxide (1.1 mL) and tert-butyl 5′-chloro-2′-((6,6,6-trifluoro-5-oxohex-3-yn-1-yl)oxy)-[1,1′-biphenyl]-3-carboxylate (5, 203 mg, 0.45 mmol) is added in 1 portion. The neon solution is stirred at room temperature for 19 h. The reaction mixture is diluted with water and filtered. The solid is dried in a vacuum oven for 2 h to afford tert-butyl 5′-chloro-2′-(2-(4-oxo-2-(phenylamino)-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-5-yl)ethoxy)-[1,1′-biphenyl]-3-carboxylate (7)
[Figure (not displayed)]
Methylmagnesium bromide (3 M in diethyl ether) (0.051 mL, 0.152 mmol) is added to a stirred solution of methyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylate (1, 30.3 mg, 0.051 mmol) in THF (2.5 mL) at −78° C. under argon. The reaction mixture quickly became dark yellow colored. After 20 min the reaction mixture is quenched with saturated aqueous ammonium chloride (0.5 mL), diluted with water (0.5 mL), and partitioned between ethyl acetate and brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and dried under high vacuum at 40° C. for 45 min to afford an orange residue. This is dissolved in THF (2.5 mL) with stirring and cooled to −78° C. under argon. Methylmagnesium bromide (3 M in diethyl ether) (0.051 mL, 0.152 mmol) is added and the reaction mixture is stirred at −78° C. under argon for 20 min. The reaction mixture is quenched with saturated aqueous ammonium chloride (0.5 mL), diluted with water (0.5 mL), and partitioned between ethyl acetate and brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via preparatory HPLC (15-57% acetonitrile in water with 0.1% TFA). Fractions containing desired product are combined and neutralized with saturated aqueous sodium bicarbonate. The acetonitrile is removed on a rotary evaporator. The residual aqueous phase is extracted three times with dichloromethane. The combined organics are dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The residue is taken up in acetonitrile and water and lyophilized to dryness to afford 3-(2-(4-chloro-2-(3-(2-hydroxypropan-2-yl)thieno[3,2-b]pyridin-7-yl)phenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (Cpd. No. 352F).
[Figure (not displayed)]
To a solution 7-(5-chloro-2-(2-(5-cyano-6-(difluoromethyl)-8-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy)phenyl)thieno[3,2-b]pyridine-3-carboxylic acid (8, 0.10 g, 0.171 mmol) in N,N-dimethylformamide (2.0 mL), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (0.098 g, 0.256 mmol) is added and mixture is stirred at room temperature for 15 min. The reaction mixture is cooled to 0° C., N,N-diisopropylethylamine (0.12 mL, 0.684 mmol) and O-methylhydroxylamine hydrochloride (8a, 0.017 g, 0.205 mmol) are added and the mixture is stirred at room temperature for 1.5 h. After completion, the reaction mixture is diluted with ethyl acetate and washed with cold water and brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude is purified by prep-HPLC to afford 7-(5-chloro-2-(2-(5-cyano-6-(difluoromethyl)-8-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)ethoxy)phenyl)-N-methoxythieno[3,2-b]pyridine-3-carboxamide (Cpd. No. 303F).
[Figure (not displayed)]
N,N-diisopropylethylamine (0.028 mL, 0.163 mmol) is added to a stirred mixture of 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylic acid (1, 32.5 mg, 0.054 mmol) and HATU (22.7 mg, 0.060 mmol) in DMF (0.3 mL) at room temperature under argon. All solids dissolved within 5 min and then shortly thereafter a lot of solids precipitated. After 20 min glycine (6.1 mg, 0.081 mmol) is added followed by more DMF (0.2 mL). The resulting mixture is sealed and stirred vigorously at room temperature for 20 min. More glycine (18.0 mg, 0.240 mmol) is added. The resulting mixture is sealed, stirred vigorously, and heated at 40° C. with a heating block for 14 h. The reaction mixture is diluted with methanol, filtered, and purified via preparatory HPLC (20-70% acetonitrile in water with 0.1% TFA). Fractions containing the desired product are combined and lyophilized to dryness to afford (7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carbonyl)glycine (Cpd. No. 398F).
[Figure (not displayed)]
1-Methylpiperazine (0.05 mL, 0.73 mmol) and methyl 7-(5-chloro-2-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-3-((4-methoxybenzyl)oxy)thieno[3,2-b]pyridine-2-carboxylate (4, 82 mg, 0.11 mmol) are dissolved in N-methyl pyrrolidinone (1.8 mL) in a screw capped vial equipped with a stir bar. The vial is sealed and heated in a heating block at 145° C. for 4.5 h. The reaction mixture is cooled to room temperature. The reaction mixture is diluted with ethyl acetate and filtered through Celite and volatile solvent removed in vacuo. The residual material is diluted with dimethylsulfoxide and purified via RP-HPLC to afford 3-(2-(4-chloro-2-(3-hydroxythieno[3,2-b]pyridin-7-yl)phenoxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (Cpd. No. 663F).
[Figure (not displayed)]
To a solution of methyl 2′-(2-(6-cyano-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5′-formyl-[1,1′-biphenyl]-3-carboxylate (7, 0.10 g, 0.22 mmol) in dichloromethane (8 mL), diethylaminosulfur trifluoride (0.052 g, 0.33 mmol) is added at 0° C. The reaction mixture is stirred at room temperature for 16 h. After completion, the reaction mixture is quenched with 10% aqueous sodium hydroxide solution at 0° C. to pH ˜7 and extracted with dichloromethane (50 mL). The organic layer is washed with water (50 mL), brine (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude. The crude is purified by combiflash column (4 g, Redisep) using 10-50% ethyl acetate in hexanes to afford methyl 2′-(2-(6-cyano-4-oxopyrido[3,4-d]pyrimidin-3(4H)-yl)ethoxy)-5′-(difluoromethyl)-[1,1′-biphenyl]-3-carboxylate (8).
[Figure (not displayed)]
N-bromosuccinimide (39.2 mg, 0.22 mmol) is added to a stirred solution of 3-(2-((5-chloro-6-methoxypyridin-2-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (3, 92 mg, 0.21 mmol) in DMF (1 mL) at room temperature. The resulting clear yellow reaction mixture is capped and stirred at room temperature for 3.5 h. More N-bromosuccinimide (19.0 mg, 0.11 mmol) is added and the reaction mixture is capped and stirred at room temperature for 2 h. The reaction mixture is diluted with ethyl acetate and washed three times with brine. The organics are dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and purified via silica gel chromatography (0-100% ethyl acetate in hexanes) to afford 3-(2-((3-bromo-5-chloro-6-methoxypyridin-2-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (4).
3-(2-((3-Bromo-5-chloro-6-methoxypyridin-2-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (4, 76.3 mg, 0.147 mmol), potassium acetate (43.4 mg, 0.44 mmol), bis(pinacolato)diboron (44.9 mg, 0.177 mmol), PdCl2(dppf).CH2Cl2 (12 mg, 0.015 mmol), and 1,4-dioxane (0.5 mL) are combined in a 1 dram vial with a stirbar and sparged with argon gas for 1 min. The resulting mixture is sealed, stirred vigorously, and heated at 90° C. with a heating block for 3 h. The reaction mixture is loaded directly onto a silica gel loading column and purified via silica gel chromatography (0-80% ethyl acetate in hexanes) to afford impure 3-(2-((5-chloro-6-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (5)
[Figure (not displayed)]
To a solution of 3-(2-((3-chloropyridazin-4-yl)oxy)ethyl)-2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-5-carbonitrile (2d, 20.0 mg, 0.049 mmol), methyl (3-(methoxycarbonyl)thieno[3,2-b]pyridin-7-yl)boronic acid (2, 15.58 mg, 0.049 mmol), Potassium Carbonate (0.15 mL, 0.150 mmol) in 1,4-dioxane (1.5 mL) is added tetrakis(triphenylphosphine)palladium(0) (5.64 mg, 0.0049 mmol) at room temperature and the mixture is degassed by bubbling argon through it for 5 min. The reaction mixture is heated to 90° C. for 16 h. After completion of the reaction, the reaction is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated brine solution, dried over anhydrous sodium sulphate, filtered, and concentrated to dryness under reduced pressure. The crude product is purified by Combiflash (12 g, RediSep column) using 1-5% methanol in dichloromethane as eluent to afford methyl 7-(4-(2-(5-cyano-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)pyridazin-3-yl)thieno[3,2-b]pyridine-3-carboxylate (3).
[Figure (not displayed)]
A flame-dried vial is charged with tert-butyl 7-(2-(2-(5-bromo-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)-5-chlorophenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (2, 106 mg, 0.150 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (10.8 mg, 0.0457 mmol), copper(I) iodide (6.2 mg, 0.033 mmol), and cesium carbonate (94 mg, 0.290 mmol). The vial is evacuated and backfilled with argon twice. Toluene (1.4 mL) and (4-methoxyphenyl)methanol (29 uL, 33 mg, 0.24 mmol) are added, and the mixture is degassed for 5 min, then stirred at 110° C. After 4 h, the mixture is allowed to cool down to room temperature and stir an additional 14 h, then diluted with EtOAc, then washed with water. The aq. phase is extracted (3×EtOAc), and the combined organic phases are dried (Na2SO4), filtered, and concentrated. Purification by column chromatography (SiO2, 0-50% EtOAc/hexane) provided 61 mg of a ca. 1:1 mixture of products tert-butyl 7-(5-chloro-2-(2-(5-((4-methoxybenzyl)oxy)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (3) and tert-butyl 7-(5-chloro-2-(2-(2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)ethoxy)phenyl)-5-methylthieno[3,2-b]pyridine-3-carboxylate (4).
Compounds made using one or more of the general methods described above are shown in Table 3. Where provided, characterization data is to the right of the compounds.
