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Methanesulfonyl chloride

Q: How can Methanesulfonyl chloride be used in pharmaceutical development?

Methanesulfonyl chloride plays a key role in the synthesis of many pharmaceutical intermediates. It is used to sulfonylate and activate specific functional groups, facilitating the incorporation of these groups into drug candidate molecules. This makes Methanesulfonyl chloride an important reagent in the early stages of pharmaceutical development and optimization.

Q: Are there any safety precautions to consider when working with Methanesulfonyl chloride?

Yes, Methanesulfonyl chloride is a corrosive and reactive compound that requires proper handling and safety precautions. It should be used in a well-ventilated area, and personal protective equipment such as gloves and goggles should be worn. Proper disposal methods must also be followed to minimize environmental impact.

Methanesulfonyl chloride is a versatile chemical compound used in organic synthesis.
It functions as a sulfonylating agent, introducing sulfonate groups into various molecular structures.
This compound is commonly employed in the preparation of pharmaceutical intermediates, polymers, and other important chemical products.
Researchers can streamline their Methanesulfonyl chloride studies using PubCompare.ai's AI-driven platform, which enables the discovery of optimal protocols from literature, preprints, and patents through intelligent comparisons.
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Most cited protocols related to «Methanesulfonyl chloride»

Synthetic Protocols for Nicotinamide Derivatives

Cited 2 times

Nicotinamide, 2-chloronicotinamide, 6-chloronicotinamide, 6-methylnicotinamide, 6-aminonicotinamide, isonicotinamide and ethyl nicotinate were purchased from Aldrich. Thionicotinamide was purchased from Acros. We also thank Peter Tyler of IRL New Zealand for several samples of nicotinamides including 5-methylnicotinamide, 6-chloronicotinamide, 6-methylnicotinamide and 6-aminonicotinamide. 5-methylnicotinamide was alternatively synthesized as reported (40 (link)).
5-Methoxynicotinamide was synthesized from the corresponding aldehyde (41 ). 5-Methoxy-3-pyridinecarboxaldehyde (400 mg, 2.92 mmol) was dissolved in 4 mL of methanol and to this solution was added hydroxylamine hydrochloride (264 mg, 3.80 mmol). The reaction mixture was allowed to stir at 25 °C for 4 h. Solvent was removed under reduced pressure, residue was redissolved in 3 mL of dry pyridine and to this solution was added methanesulfonyl chloride (435 mg, 3.80 mmol). The mixture was stirred at 25 °C for 2 h, and then water and ethyl acetate were added. The combined organic layer was dried over Na₂SO₄. Column chromatography (hexanes: ethyl acetate = 4:1) afforded 320 mg (2.39 mmol, 82% yield) of 3-cyano-5-methoxypyridine as a white solid. ¹H NMR (400 MHz, CDCl₃), δ ppm: 8.49 (d, J= 2.8 Hz, 1H), 8.46 (d, J= 1.5 Hz, 1H), 7.37 (dd, J= 1.6, 2.8 Hz, 1H), 3.89 (s, 3H). Hydrogen peroxide (4 mL) was added dropwise to a solution of 3-cyano-5-methoxypyridine (320 mg, 2.39 mmol) and K₂CO₃ (790 mg, 5.72 mmol) in 3 mL of DMSO, the mixture was stirred for one hour before it was diluted with water and lyophilized to dryness. The crude product was purified by column chromatography (ethyl acetate: ethanol = 10:1) followed by recrystallization in ethyl acetate to afford 200 mg (1.32 mmol, 55% yield) of 5-methoxynicotinamide as white solid. ¹H NMR (400 MHz, DMSO), δ ppm: 8.62 (d, J= 1.7 Hz, 1H), 8.40 (d, J= 2.9 Hz, 1H), 8.13 (s, br, 1H), 7.74 (dd, J= 1.8, 2.8 Hz, 1H), 7.59 (s, br, 1H), 3.86 (s, 3H); ¹³C NMR (100 MHz, DMSO), δ ppm: 55.7, 118.8, 130.3, 140.1, 140.7, 155.0, 166.2; HRMS (ESI): calcd for C₇H₈N₂O₂ 152.0586, found 152.0587.
4-Methoxynicotinamide was synthesized from the corresponding aldehyde (41 ). 4-Methoxy-3-pyridinecarboxaldehyde (180 mg, 1.31 mmol) was dissolved in 2 mL of methanol and to this solution was added hydroxylamine hydrochloride (118 mg, 1.70 mmol). The reaction mixture was allowed to stir at room temperature for 4 h. Solvent was removed under reduced pressure, residue was redissolved in 2 mL of dry pyridine and to this solution was added methanesulfonyl chloride (195 mg, 1.70 mmol). The mixture was stirred at room temperature for 2 h, and then water and ethyl acetate were added. The combined organic layer was dried over Na₂SO₄. Column chromatography (hexanes: ethyl acetate = 1:2) afforded 135 mg (1 mmol, 78% yield) of 3-cyano-4-methoxypyridine as white solid. ¹H NMR (400 MHz, CDCl₃), δ ppm: 8.67 (s, 1H), 8.62 (d, J= 6.0 Hz, 1H), 6.90 (d, J= 6.0 Hz, 1H), 3.99 (s, 3H). Hydrogen peroxide (1.67 mL) was added dropwise to a solution of 3-cyano-4-methoxypyridine (135 mg, 1mmol) and K₂CO₃ (333 mg, 2.4 mmol) in 3 mL of DMSO, the mixture was stirred for one hour before it was diluted with water and lyophilized to dryness. The crude product was purified by column chromatography (ethyl acetate: ethanol = 10:1) followed by recrystallization in ethyl acetate to afford 100 mg (0.66 mmol, 66% yield) of 4-methoxynicotinamide as white solid. ¹H NMR (400 MHz, DMSO), δ ppm: 8.70 (s, 1H), 8.51 (d, J= 5.8 Hz, 1H), 7.64 (s, br, 1H), 7.61 (s, br, 1H), 7.15 (d, J= 5.9 Hz, 1H), 3.93 (s, 3H); ¹³C NMR (125 MHz, DMSO), δ ppm: 57.0, 108.7, 117.7, 151.5, 154.2, 165.2, 168.9; HRMS (ESI): calcd for C₇H₈N₂O₂ 152.0586, found 152.0587.
2-Aminoisonicotinamide was synthesized as described before (42 (link)) with several modifications. Briefly, acetylation of 2-amino-4-picoline followed by oxidation using KMnO₄ gave 2-N-acetylamido-isonicotinic acid. This compound was subjected to amidation in the presence of DCC and ammonia in methanol to yield 2-N-acetylamido-isonicotinamide. Further reaction of 2-N-acetylamido-isonicotinamide with ammonia in methanol provided the desired 2-aminoisonicotinamide in modest yield, ¹H NMR matches reported data
Phenyl nicotinate was synthesized from nicotinoyl chloride hydrochloride. To a 100 mL round-bottom flask were added nicotinoyl chloride hydrochloride (770 mg, 4.33 mmol), 5 mL of triethylamine and 20 mL of THF. To this mixture was added 4 mL of pyridine dropwise. After stirring for 30 min at 25 °C, phenol (610 mg, 6.49 mmol) was added. The reaction was kept at 25 °C overnight, precipitate was filtered off and solution was evaporated under reduced pressure. The residue was redissolved in water and extracted with CH₂Cl₂. The combined organic layer was washed with brine and dried over anhydrous Na₂SO₄. Solvent was then concentrated in vacuo and crude product was recrystallized from ethyl acetate. ¹H NMR (500 MHz, CDCl₃), δ ppm: 9.41 (s, 1H), 8.86 (dd, J = 1.7, 4.9 Hz, 1H), 8.46 (dt, J = 2.0, 8.0 Hz, 1H), 7.47 (stack, 3H), 7.32 (t, J = 7.3 Hz, 1H), 7.23 (m, 2H).
1-Methylnicotinamide was synthesized similarly to the method reported by Martin and Hull (43 (link)). Briefly, three equivalents of iodomethane was added to a solution of nicotinamide in 2 mL of methanol. The reaction was allowed to stir at room temperature and monitored by TLC. When the reaction was complete (after approximately 30 hours), the solid was filtered off and dried under reduced pressure. The resulting product was purified by recrystallization from methanol. ¹H NMR (500 MHz, DMSO), δ ppm: 9.4 (s, 1H), 9.11 (d, J= 6.1 Hz, 1H), 8.90 (d, J= 8.2 Hz, 1H), 8.51 (s, br, 1H), 8.25 (dd, J= 6.1, 8.1 Hz, 1H), 8.14 (s, br, 1H), 4.42 (s, 3H). 1-Methyl-isonicotinamide was prepared similarly.

French J.B., Cen Y., Vrablik T.L., Xu P., Allen E., Hanna-Rose W, & Sauve A.A. (2010). Characterization of Nicotinamidases: Steady-State Kinetic Parameters, Class-wide Inhibition by Nicotinaldehydes and Catalytic Mechanism. Biochemistry, 49(49), 10421-10439.

Publication 2010

Synthesis of 3-((2,6-bis(ethylthio)pyridin-4-yl)methyl)-6-bromo-2-methoxyquinoline

Cited 2 times

Sodium hydride (60% w/w, 1.44 g, 36.1 mmol) in DMF (25 mL) at 0 °C was added ethanethiol (2.70 mL, 36.1 mmol) dropwise. The mixture foamed up as hydrogen gas was released. The mixture was stirred at 0 °C for 15 min, then a solution of 2,6-dichloroisonicotinic acid (2.05 g, 11.6 mmol) in anhydrous DMF (9 mL) was added dropwise at 0 °C. The mixture was then stirred at 150 °C for 17 h. The mixture was diluted in water, dissolving the white salts. The aqueous mixture was purged with air to remove most of the stench. 2 M hydrochloric acid was added until pH reached ∼ 3, when white solids crashed out. The solids were collected by filtration, washed with ice-cold water, dried to yield 2,6-bis(ethylthio)isonicotinic acid (2.82 g, 100%) as light yellow solid which was used directly in the next step. ¹H NMR (CDCl₃) δ 7.40 (s, 2H), 3.19 (q, J = 7.3 Hz, 4H), 1.39 (t, J = 7.3 Hz, 6H). Found: [M + H] = 244.5.
Borane dimethyl sulfide complex (3.30 mL, 34.8 mmol) and trimethyl borate (3.90 mL, 34.8 mmol) were added to a solution of 2,6-bis(ethylthio)isonicotinic acid (2.82 g, 11.6 mmol) in THF (100 mL, dist. Na) at 0 °C. The solution was then warmed to 20 °C and was stirred for 18 h at 20 °C. The reaction mixture was cooled to 0 °C, MeOH (20 mL) was added to quench the reaction and the solvent was evaporated in the fume hood. The residue was partitioned between EtOAc and water, extracted with EtOAc (3x), dried with MgSO₄, filtered and the solvent was evaporated. Column chromatography (4:1 hexanes:EtOAc) gave (2,6-bis(ethylthio)pyridin-4-yl)methanol (2.50 g, 94%) as a white solid. ¹H NMR (CDCl₃) δ 6.87 (s, 2H), 4.61 (s, 2H), 2.58 (s, 6H). Found: [M + H] = 202.5.
To a solution of (2,6-bis(ethylthio)pyridin-4-yl)methanol (2.48 g, 10.8 mmol) in anhydrous DCM (42 mL) was added triethylamine (2.20 mL, 16.2 mmol) dropwise, followed by methanesulfonyl chloride (1.10 mL, 14.2 mmol). The mixture was stirred at 0 °C for 10 min, then allowed to stir at 20 °C for 1 h. The mixture was quenched with saturated sodium bicarbonate solution. The aqueous mixture was extracted with dichloromethane (2x). The combined extract was washed with brine, dried with MgSO₄ and concentrated to afford the crude product as a yellow oil. The crude intermediate was diluted in acetone (84 mL). Lithium chloride (1.85 g, 43.64 mmol) was added. The suspension was stirred at room temperature overnight. The mixture was concentrated in vacuo and adsorbed onto silica. Flash chromatography using a mixture of 98:2 hexane/ethyl acetate gave 4-(chloromethyl)-2,6-bis(ethylthio)pyridine (2.26 g, 84%) as a light yellow oil. ¹H NMR (CDCl₃) δ 6.87 (s, 2H), 4.61 (s, 2H), 2.58 (s, 6H). Found: [M + H] = 202.5.
A mixture of (6-bromo-2-methoxyquinolin-3-yl)boronic acid (2.56 g, 9.10 mmol), 4-(chloromethyl)-2,6-bis(ethylthio)pyridine (2.25 g, 9.10 mmol) and Cs₂CO₃ (5.93 g, 18.19 mmol) in toluene-DMF (60 mL, 2:1) was degassed under N₂, then added Pd(PPh₃)₄ (0.52 g, 0.45 mmol), and heated at 90 °C for 1.5 h. Reaction mixture was cooled to 20 °C, filtered through a plug of celite, added water and extracted with EtOAc (x4). Organic layer washed with brine, dried with Na₂SO₄, filtered and the solvent was evaporated to give a yellow residue. Purification by flash column chromatography with silica using hexane:EtOAc (9:1) gave 3-((2,6-bis(ethylthio)pyridin-4-yl)methyl)-6-bromo-2-methoxyquinoline (AB-12) (1.80 g, 47%) as a white solid. ¹H NMR (CDCl₃) δ 7.80 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 8.9 Hz, 1H), 7.65 (dd, J = 8.9, 2.2 Hz), 7.57 (s, 1H), 6.72 (s, 2H), 4.05 (s, 3H), 3.87 (s, 2H), 2.57 (s, 6H). Found: [M + H] = 421.8.

Sutherland H.S., Tong A.S., Choi P.J., Blaser A., Conole D., Franzblau S.G., Lotlikar M.U., Cooper C.B., Upton A.M., Denny W.A, & Palmer B.D. (2019). 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. Bioorganic & Medicinal Chemistry, 27(7), 1292-1307.

Publication 2019

Synthesis and Characterization of Nitric Oxide-Releasing Nanoparticles

Cited 2 times

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Publication 2020

Synthesis of N-Substituted Decahydropyrrolo[1,2-a][1,5]diazocine Derivatives

Cited 2 times

¹H NMR spectra were measured at 300 MHz. ¹H chemical shifts are reported with CHCl₃ (7.27 ppm), DHO (4.79 ppm) and CD₃OH (3.34 ppm) as internal standards. Final products were purified by HPLC on a C18 reverse phase semi-preparative column with solvent A (0.1% of TFA in water) and solvent B (0.1% of TFA in CH₃CN) as eluents and the purity of the final products was checked by analytical HPLC using the C18 reverse phase column to be over >95% purity.
tert-butyl ((5S,8S,10aR)-8-(benzhydrylcarbamoyl)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a] [1,5]diazocin-5-yl)carbamate (8). Isovaleryl chloride (0.2 mL) and N,N-diisopropylethylamine (0.4 mL) were added to a solution of 6 (340 mg, 1 mmol) in CH₂Cl₂ (20 mL). The solution was stirred at room temperature for 3 h then concentrated. The residue was purified by chromatography to give an amide. 2N LiOH solution (2.0 mL) was added to a solution of this amide in 1,4-dioxane (3.0 mL). After TLC showed all of the amide had been consumed, the mixture was neutralized with 1N HCl to pH 5 and then extracted with EtOAc (3 × 10 mL). The combined organic layers were dried over Na₂SO₄ and then concentrated to give the acid 7 (340 mg, 82% over two steps), which was used directly, without purification, in the next step. To a solution of 7 (105 mg, 0.25 mmol) in CH₂Cl₂ (10 mL) was added aminodiphenylmethane (55 mg, 0.3 mmol), EDC (58 mg, 0.3 mmol), HOBt (45 mg, 0.33 mmol) and N,N-diisopropylethylamine (0.5 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to give 8 (120 mg, 82%). ¹H NMR (CDCl₃): δ 7.70 (brd, J = 7.0 Hz, 1H), 7.35–7.16 (m, 10H), 6.25 (d, J = 7.5 Hz, 1H), 5.90 (brd, J = 7.0 Hz, 1H), 4.70 (m, 1H), 4.45 (m, 1H), 4.08–3.70 (m, 3H), 2.80–2.50 (m, 3H), 2.42 (m, 1H), 2.30–1.50 (m, 7H), 1.47 (brs, 9H), 1.02 (m, 6H); ESI MS:m/z 577.3 (M + H)⁺.
(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodeca-hydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide (2). HCl (4N in 1,4-dioxane, 1 mL) was added to a solution of 8 (58 mg, 0.1 mmol) in MeOH (10 mL). The solution was stirred at room temperature overnight and then concentrated to give an ammonium salt. To a mixture of this salt in CH₂Cl₂ (10 mL) was added L-N-Boc-N-methyl-alanine (30 mg, 0.15 mmol), EDC (29 mg, 0.15 mmol), HOBt (22 mg, 0.16 mmol) and N,N-diisopropylethylamine (0.3 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to furnish an amide. To a solution of this amide in 5 mL of MeOH was added HCl solution (4N in 1,4-dioxane, 1 mL). The solution was stirred at room temperature overnight and then concentrated to give crude product which was purified by HPLC to give pure compound 2 (salt with TFA, 48 mg, 74% over three steps). The gradient ran from 70% A and 30% B to 50% A and 50% B in 30 min. The purity was determined by reverse analytical HPLC to be over 95%. ¹H NMR (CD₃OD, 300 M Hz): δ 8.97 (d, J = 7.5 Hz, 1H), 7.38–7.25 (m, 10H), 6.16 (d, J = 7.5 Hz, 1H), 4.80 (m, 1H), 4.58 (m, 1H), 4.25 (m, 1H), 3.96 (m, 3H), 3.47 (m, 1H), 2.72 (s, 3H), 2.49 (d, J = 7.2 Hz, 2H), 2.37–2.32 (m, 1H), 2.15–2.00 (m, 6H), 1.84–1.80 (m, 1H), 1.56 (d, J = 5.4 Hz, 3H), 1.00 (d, J = 6.0 Hz, 6H), ESI-MS m/z 562.3 (M + H)⁺.
(5S,8S,10aR)-5-((S)-3-(1H-indol-3-yl)-2-(methylamino)propanamido)-N-benzhydryl-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide (3). HCl (4N in 1,4-dioxane, 1 mL) was added to a solution of 8 (58 mg, 0.1 mmol) in MeOH (10 mL). The solution was stirred at room temperature overnight and then concentrated to give an ammonium salt. To a mixture of this salt in 10 mL of CH₂Cl₂ was added L-Nα-Boc-Nα-methyl-tryptophan (48 mg, 0.15 mmol), EDC (30 mg, 0.15 mmol), HOBt (22 mg, 0.16 mmol) and N,N-diisopropylethylamine (0.3 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to furnish an amide. To a solution of this amide in 5 mL of MeOH was added HCl (4N in 1,4-dioxane. 1 mL). The solution was stirred at room temperature overnight and then concentrated to give crude product which was purified by HPLC to give 3 (salt with TFA, 49 mg, 63% over three steps). The gradient ran from 70% A and 30% B to 40% A and 60% B in 30 min. The purity was determined by reverse analytical HPLC to be >95%. ¹H NMR (CD₃OD, 300 M Hz): δ 8.88 (d, J = 8.4 Hz, 1H), 7.33–7.08 (m,13H), 6.95 (m, 2H), 6.10 (m, 1H), 4.40 (m, 1H), 4.34 (m, 1H), 4.27(m, 1H), 4.23 (m, 1H), 3.97 (m, 2H), 3.83 (m, 2H), 3.44 (m, 1H), 3.10 (m, 2H), 2.73 (2S, 3H), 2.52 (m, 2H), 2.36 (m, 1H), 2.18–1.72 (m, 6H), 1.00 (m, 6H), ESI-MS m/z 677.4 (M + H)⁺.
tert-butyl methyl((S)-1-(((5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-(((R)-1-phenylprop-2-yn-1-yl) carbamoyl)decahydropyrrolo[1,2-a][1,5]diazocin-5-yl)amino)-1-oxopropan-2-yl)carbamate (10). S-1-phenylprop-2-yn-1-amine (79 mg, 0.6 mmol), EDC (116 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and N,N-diisopropylethylamine (1 mL) were added to a solution of 7 (205 mg, 0.5 mmol) in CH₂Cl₂ (15 mL) at 0°C. The mixture was stirred at room temperature for 6 h then concentrated. The residue was purified by chromatography to give an amide. To a solution of this amide in MeOH (15 mL) was added HCl solution (4N in 1,4-dioxane, 2 mL). The solution was stirred at room temperature overnight and then concentrated to give an ammonium salt. To a mixture of this salt in CH₂Cl₂ (20 mL) was added L-N-Boc-N-methyl-alanine (124 mg, 0.6 mmol), EDC (120 mg, 0.6 mmol), HOBt (83 mg, 0.6 mmol) and N,N-diisopropylethylamine (1 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to give 11 (210 mg, 69% over three steps). ¹H NMR (300 MHz, CDCl₃, TMS) δ 7.58 (m, 1H), 7.54–7.49 (m, 2H), 7.36–7.20 (m, 4H), 5.95 (dd, J = 8.5, 2.4 Hz, 1H), 4.70 (m, 1H), 4.60–4.45 (m, 2H), 3.95 (m, 1H), 3.92–3.80 (m, 2H), 2.79 (s, 3H), 2.70–2.35 (m, 5H), 2.35–1.75 (m, 7H), 1.50 (brs, 9H), 1.33 (d, J = 7.2 Hz, 3H), 1.05–0.95 (m, 6H); ESI MS m/z 610.3 (M+H)⁺.
(5S,8S,10aR)-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxo-N-((S)-(1-(10-(6-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanamido)decyl)-1H-1,2,3-triazol-4-yl)(phenyl)methyl)decahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide (4). Z-6-aminohexanoic acid (790 mg, 3 mmol), EDC (590 mg, 3 mmol), HOBt (395 mg, 3 mmol) and triethylamine (2 mL) were added to a solution of 10-amino-1-decanol (9, 520 mg, 3 mmol) in CH₂Cl₂ (15 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to furnish an amide. Methanesulfonyl chloride (0.3 mL) and triethylamine (1 mL) in CH₂Cl₂ (20 mL) were added to a solution of this amide at 0°C. The solution was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to yield a mesylate. Sodium azide (200 mg) was added to a solution of this mesylate in DMF (10 mL) and the mixture was stirred at 110°C overnight and then partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was dried over Na₂SO₄ and then concentrated. The residue was purified by chromatography to provide 10 (650 mg, 49% over three steps). CuSO₄ (25 mg, 0.1 mmol) and sodium L-ascorbate (100 mg, 0.5 mmol) in water (5 mL) were added to a solution of 10 (122 mg, 0.2 mmol) and 9 (90 mg, 0.2 mmol) in acetonitrile (3 mL) and tert-butanol (3 mL). The mixture was stirred at room temperature overnight and then partitioned between EtOAc (30 mL) and brine (20 mL). The organic layer was dried over Na₂SO₄ and then concentrated. The residue was purified by chromatography to give a triazole which, mixed with 10% Pd-C (100 mg) in MeOH (20 mL), was stirred under H₂ overnight and then filtered through celite. The filtration was concentrated to yield an amine. To a solution of this amine in CH₂Cl₂ (20 mL) was added (+)-biotin N-hydroxy-succinimide ester (78 mg, 0.2 mmol) and N,N-diisopropylethylamine (0.5 mL). The solution was stirred at room temperature overnight and then concentrated to give a residue which was purified by chromatography to afford a biotinylated amide. To a solution of this amide in MeOH (10 mL) was added HCl solution (4N in 1,4-dioxane, 2 mL). The mixture was stirred overnight and then concentrated to furnish a crude product which was purified by a semi-preparative HPLC using a reverse phase C18 column to give pure compound 4 (salt with TFA, 98 mg, 43% over four steps). The gradient ran from 70% of A and 30% of B to 40% of A and 60% of B in 30 min. The purity of the compound was determined by an analytical HPLC using a reverse phase C18 column to be over 95%. ¹H NMR (D₂O): δ 7.70 (brs, 1H), 7.35–7.05 (m, 5H), 6.05 (brs, 1H), 4.70 (m, 1H), 4.50–4.30 (m, 2H), 4.30–4.05 (m, 3H), 4.05–3.60 (m, 2H), 3.60–2.80 (m, 5H), 2.80–2.50 (m, 6H),2.40–1.05 (m, 44H), 0.80 (m, 6H); ESI MS: m/z 1047.6 (M + H)⁺.
2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-5-((10-(4-((S)-((5S,8S,10aR)-5-((S)-2-(methylamino)prop-anamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamido)(phenyl) methyl)-1H-1,2,3-triazol-1-yl)decyl)carbamoyl)benzoic acid (5). Benzyl chloroformate (0.5 mL) and triethylamine (2 mL) were added to a solution of 10-amino-1-decanol (10, 520 mg, 3 mmol) in CH₂Cl₂ (15 mL) at 0°C. The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to furnish a carbamate. Methanesulfonyl chloride (0.5 mL) was added dropwise at 0°C to a solution of this carbamate in CH₂Cl₂ (20 mL) with triethylamine (1 mL). The solution was stirred at room temperature for 6 h and then concentrated. The residue was purified by chromatography to yield a mesylate. Sodium azide (300 mg) was added to a solution of this mesylate in DMF (10 mL). The mixture was stirred at 110°C overnight and then partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was dried over Na₂SO₄ and then concentrated. The residue was purified by chromatography to provide 12 (650 mg, 66% over three steps.) A mixture of CuSO₄ (25 mg, 0.1 mmol) and sodium L-ascorbate (100 mg, 0.5 mmol) in water (5 mL) was added to a solution of 11 (122 mg, 0.2 mmol) and 12 (66 mg, 0.2 mmol) in acetonitrile (3 mL) and tert-butanol (3 mL). The mixture was stirred at room temperature overnight and then partitioned between EtOAc (30 mL) and brine (20 mL). The organic layer was dried over Na₂SO₄ and then concentrated. The residue was purified by chromatography to give a triazole. A mixture of this triazole and 100 mg of 10% Pd-C in MeOH (20 mL) was stirred under H₂ overnight and then filtered through celite. The filtration was concentrated to yield an amine. To a solution of this amine in CH₂Cl₂ (20 mL) was added 5-carboxyfluorescein N-succinimidyl ester (95 mg, 0.2 mmol) and N,N-diisopropylethylamine (0.5 mL). The solution was stirred at room temperature overnight and then concentrated. The residue was purified by chromatography to afford a biotinylated amide. To a solution of this amide in MeOH (10 mL) was added HCl (4N in 1,4-dioxane, 2 mL). The mixture was stirred overnight and then concentrated to furnish a crude product which was purified by semi-preparative HPLC using a reverse phase C18 column to give compound 5 (salt with TFA, 72 mg, 34% over four steps). The gradient ran from 70% of A and 30% of B to 40% of A and 60% of B in 30 min. The purity of the compound was determined by analytical HPLC using a reverse phase C18 column to be over 95%. ¹H NMR (CD₃OD, 300 MHz): δ 8.48 (s, 1H), 8.22 (m, 1H), 7.70 (s, 1H), 7.50–7.20 (m, 5H), 6.75 (brs, 2H), 6.70–6.50 (m, 4H), 6.30 (brs, 1H), 4.70 (m, 1H), 4.65–4.50(m, 2H), 4.40–4.30 (m, 2H), 4.30–4.15 (m, 2H), 4.05–3.80 (m, 3H), 3.50–3.40 (m, 2H), 2.70 (brs, 3H), 2.52–2.01 (m, 7H), 2.01–1.60 (m, 7H), 1.60–1.50 (m, 3H), 1.50–1.20 (m, 11H), 0.95 (m, 6H); ESI MS: m/z 1066.5 (M + H)⁺.

Cai Q., Sun H., Peng Y., Lu J., Nikolovska-Coleska Z., McEachern D., Liu L., Qiu S., Yang C.Y., Miller R., Yi H., Zhang T., Sun D., Kang S., Guo M., Leopold L., Yang D, & Wang S. (2011). A potent and orally active antagonist of multiple inhibitor of apoptosis proteins (IAPs) (SM-406/AT-406) in clinical development for cancer treatment. Journal of medicinal chemistry, 54(8), 2714-2726.

Publication 2011

Synthesis of Compounds CP2 and TP3

Cited 1 time

Compounds CP2 and TP3 were synthesized as described earlier. Briefly, a selective hydroboration of compound 1 with borane followed by hydrogen peroxide, mesylation with methanesulfonyl chloride, and displacement with adenine provided CP2 or TP3 [22 ].

Trushina E., Rana S., McMurray C.T, & Hua D.H. (2009). Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons. BMC Neuroscience, 10, 73.

Publication 2009

Adenine Boranes fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether methanesulfonyl chloride Peroxide, Hydrogen

Most recents protocols related to «Methanesulfonyl chloride»

Synthesis of Functionalized Pyrrolidine Nitroxides

Method A: N,N-diisopropylethylamine (DIPEA) was added dropwise within 6 h to a stirred solution of 1 and methanesulfonyl chloride 1.4 g in dry chloroform, the amount and ratio of the reagents is shown in Table 2. The mixture was stirred overnight, washed with water and dried with MgSO₄. The solution was concentrated in a vacuum and separated using column chromatography on silica gel, eluent chloroform; yields of 3 and 4 are shown in the Table 2.
2,2,5,5-Tetraethyl-3,4-bis((methylsulfonyloxy)methyl)pyrrolidin-1-oxyl (3), yellow crystals, m.p. 73–75 °C (hexane). IR (KBr) ν_max: 1348, 1170 (OMs). ¹H NMR (300 MHz; CD₃OD, Zn/CF₃COOH, δ): 1.06 (t, J_t = 7.4 Hz, 6H), 1.07 (t, J_t = 7.4 Hz, 6H), 1.88 (dq, J_d = 14.7 Hz, J_q = 7.4 Hz, 2H), 2.00 (q, J_q = 7.4 Hz, 4H), 2.06 (dq, J_d = 14.7 Hz, J_q = 7.4 Hz, 2H), 2.67–2.78 (m, 2H), 3.18 (s, 6H), 4.44–4.55 (m, 4H). Anal. Calcd for C₁₆H₃₂NO₇S₂: C, 46.36; H, 7.78; N, 3.38; S, 15.47; found: C, 46.49; H, 7.50; N, 3.57.
2,2,5,5-Tetraethyl-3-(hydroxymethyl)-4-((methylsulfonyloxy)methyl)pyrrolidin-1-oxyl (4), yellow crystals, m.p. 66–67 °C (hexane). IR (KBr) ν_max: 3386 (OH), 1359, 1180 (OMs). ¹H NMR (300 MHz; CD₃OD, Zn/CF₃COOH, δ): 1.04 (t, J_t = 7.4 Hz, 6H), 1.05 (t, J_t = 7.4 Hz, 3H), 1.06 (t, J_t = 7.4 Hz, 3H), 1.77–2.12 (m, 8H), 2.32 (ddd, J_d1 = 11.8 Hz, J_d2 = 5.6, J_d3 = 4.9 Hz, 1H), 2.68 (ddd, J_d1 = 11.8 Hz, J_d2 = 7.3 Hz, J_d3 = 3.6 Hz, 1H), 3.14 (s, 3H), 3.78 (dd, J_d1 = 11.7 Hz, J_d2 = 4.9 Hz, 1H), 3.83 (dd, J_d1 = 11.7 Hz, J_d2 = 5.6 Hz, 1H), 4.43 (dd. J_d1 = 11.0 Hz, J_d2 = 7.3 Hz, 1H), 4.54 (dd, J_d1 = 11.0 Hz, J_d2 = 3.6 Hz, 1H). ¹³C{¹H} (75 MHz; CD₃OD, Zn/CF₃COOH, δ): 6.71, 6.77, 23.5, 23.7, 28.8, 28.9, 35.3, 48.1, 49.9, 58.42, 66.5, 69.7, 70.1. Anal. Calcd for C₁₅H₃₀NO₅S: C, 53.54; H, 8.99; N, 4.16; S, 9.53; found: C, 53.38; H, 8.96; N, 4.20; S, 9.50.
Method B: Methanesulfonyl chloride (227 mg, 1.98 mmol) was added dropwise to a stirred solution of 8 (274 mg, 0.57 mmol) and DIPEA (335 mg, 2.59 mmol)) in dry chloroform (10 mL). The mixture was stirred at ambient temperature for 3 days (TLC control on silica gel, chloroform—methanol 100:1, visualization with UV-254), washed with water and dried with Na₂CO₃. The solution was concentrated in vacuum. The residue was purified using column chromatography on silica gel, eluent chloroform—methanol 100:1 to give 9 (247mg, 74%).
3-(((tert-Butoxycarbonyl)amino)methyl)-2,2,5,5-tetraethyl-4-(((methylsulfonyl)oxy)methyl)pyrrolidin-1-oxyl (9), yellow crystals, m.p. 135–136 °C (hexane—chloroform 25:1). IR (KBr) ν_max: 3363, 1513 (NH), 1675 (C=O), 1358, 1178 (OMs). UV (EtOH) λ_max (log ε): 239 (3.34). Anal. Calcd for C₂₀H₃₉N₂O₆S: C, 55.15; H, 9.02; N, 6.43; S, 7.36; found: C, 54.89; H, 9.06; N, 6.38; S, 7.19. HRMS (EI/DFS) m/z: [M]⁺ calcd for C₂₀H₃₉N₂O₆S 435.2523, found 435.2525.

Usatov M.S., Dobrynin S.A., Polienko Y.F., Morozov D.A., Glazachev Y.I., An’kov S.V., Tolstikova T.G., Gatilov Y.V., Bagryanskaya I.Y., Raizvikh A.E., Bagryanskaya E.G, & Kirilyuk I.A. (2024). Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl. International Journal of Molecular Sciences, 25(3), 1550.

Publication 2024

Mesylation of Alcohol Intermediate

To a solution of 2 (4.12 g, 15.7 mmol) in DCM (55 mL) cooled on an ice bath triethylamine (4.40 mL, 31.7 mmol) was added and the mixture was stirred for 20 min. The reaction mixture was heated to rt, methanesulfonyl chloride (1.20 mL, 15.5 mmol) was added and the reaction mixture was stirred at rt for 3 h. After the reaction was finished dichloromethane (30 mL) was added and the organic phase was washed with brine (140 mL). Organic phase was dried over Na₂SO₄, filtered and the solvent removed in vacuo. The crude oily product was used in the next step without further purification.

Durcik M., Cruz C.D., Scorciapino M.A., Ilaš J., Tammela P., Ceccarelli M., Mašič L.P, & Tomašič T. (2024). Benzothiazole DNA gyrase inhibitors and their conjugates with siderophore mimics: design, synthesis and evaluation. RSC Advances, 14(5), 2905-2917.

Publication 2024

Synthesis of N-(3-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)phenyl)methanesulfonamide

Not available on PMC !

Example 25

[Figure (not displayed)]

3-(7-Chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)aniline (12 mg, 0.04 mmol) was placed in a vial with dichloromethane (2 mL) and TEA (0.1 mL) and cooled to 0° C. Methanesulfonyl chloride (6 mg, 0.06 mmol) was added and the solution was stirred at rt for 16 h. Water (3 mL) was added and the aqueous extracted with ethyl acetate (2×5 mL). The combined organics were dried and concentrated and the residue purified by silica chromatography to afford N-(3-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)phenyl)methanesulfonamide (MS: [M+1]⁺399.0).

US11873291B2. Quinoline cGAS antagonist compounds (2024-01-16). ImmuneSensor Therapeutics, Inc. [US], The Board of Regents of the University of Texas System [US]. Inventors: Jian Qiu [US], Qi Wei [US], Matt Tschantz [US], Heping Shi [US], Youtong Wu [US], Hulling Tan [US], Lijun Sun [US], Chuo Chen [US], Zhijian Chen [US].

Patent 2024

Anabolism aniline Chromatography ethyl acetate imidazole methanesulfonamide methanesulfonyl chloride Methylene Chloride Silicon Dioxide

Synthesis of Mesylated Hydroxymethyl Derivative

To a solution of hydroxymethyl derivative 5 (1.50 g, 4.56 mmol) in dry pyridine (25.0 mL) methanesulfonyl chloride (2.11 mL, 27.36 mmol, 6 eq.) was added, and the mixture was stirred at room temperature for 12 hours. Then, toluene (30 mL) was added, and the mixture was concentrated under vacuum to dryness. The residue was diluted with water (25 mL) and then extracted with DCM (3 × 25 mL). The organic phase was washed with brine solution (3 × 50 mL), dried over Na₂SO₄, filtered and then evaporated. The crude product was purified by column chromatography on silica gel using n-hexane : EtOAc (1 : 1) as eluent and then it was crystallised in Et₂O to afford the product as a white solid (1.4 g, 76%).

Khdar Z.A., Le T.M., Schelz Z., Zupkó I, & Szakonyi Z. (2024). Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohol regioisomers. RSC Medicinal Chemistry, 15(3), 874-887.

Publication 2024

Synthesis of 5-(p-Chlorophenyl)-6-(1-{[p-(Trifluoromethyl)Phenyl]Methyl}-1H-Pyrazol-4-yl)-4-Pyrimidinylamine Derivative

Not available on PMC !

Example 45

A stirring solution of 5-(p-chlorophenyl)-6-(1-{[p-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-4-yl)-4-pyrimidinylamine (example 4, 150 mg, 0.35 mmol) in THF (1.8 mL) under an inert atmosphere of N2 was treated with sodium hydride (56 mg of a 60% dispersion in oil, 1.40 mmol) and the resulting mixture was stirred for 30 minutes at room temperature. Methanesulfonyl chloride (41 μL, 0.53 mmol) was added via syringe and the resulting mixture was stirred at room temperature for 2 hours. The reaction was carefully poured onto ice/water and the product was extracted with ethyl acetate. The organic layer was washed with 1 N aqueous HCl solution and brine, dried over anhydrous MgSO4, filtered and evaporated. The crude product was purified by silica-gel column chromatography, eluting with hexanes/EtOAc mixture to provide the title compound as a white solid (63 mg, 0.124 mmol, 35%). HPLC/MS (ESI) m/z 508.3 (M⁺+H⁺). Method 1 retention time=2.70 min.

US11866421B2. Pyrimidine and pyridine amine compounds and usage thereof in disease treatment (2024-01-09). Epigen Biosciences, Inc. [US]. Inventors: Graham Beaton [US], Fabio Tucci [US], Satheesh Ravula [US], Suk Joong Lee [US], Chandravadan Shah [US].

Patent 2024

Amines Atmosphere brine Chromatography ethyl acetate Gel Chromatography Hexanes High-Performance Liquid Chromatographies Ice methanesulfonyl chloride pyrazole Retention (Psychology) Silica Gel Silicon Dioxide sodium hydride Sulfate, Magnesium Syringes

Top products related to «Methanesulfonyl chloride»

Methanesulfonyl chloride by Merck Group

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Methanesulfonyl chloride is a colorless, volatile liquid chemical compound. It is primarily used as a reagent in organic synthesis reactions, particularly in the preparation of various sulfonate esters and sulfonamides.

Millex lcr by Merck Group

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The Millex-LCR is a high-flow, low-binding syringe filter designed for the filtration of cell culture media, buffers, and other aqueous solutions. It features a low hold-up volume and a high flow rate, making it suitable for a variety of laboratory applications.

Prep hplc by Waters Corporation

Sourced in United States

Prep-HPLC is a high-performance liquid chromatography (HPLC) system designed for preparative-scale purification. It provides efficient separation and purification of compounds from complex mixtures.

P4250 by Interchim

The P4250 is a laboratory equipment product manufactured by Interchim. It is designed to perform a core function, but a detailed description cannot be provided while maintaining an unbiased and factual approach without extrapolation.

Triethylamine by Merck Group

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Triethylamine is a clear, colorless liquid used as a laboratory reagent. It is a tertiary amine with the chemical formula (CH3CH2)3N. Triethylamine serves as a base and is commonly employed in organic synthesis reactions.

Sodium azide by Merck Group

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Sodium azide is a chemical compound commonly used in laboratory applications. It functions as a preservative and acts as a source of the azide ion, which can be utilized in various experimental and analytical procedures. This product is intended for use by qualified professionals in controlled laboratory settings.

Hydrochloric acid (hcl) by Merck Group

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Hydrochloric acid is a commonly used laboratory reagent. It is a clear, colorless, and highly corrosive liquid with a pungent odor. Hydrochloric acid is an aqueous solution of hydrogen chloride gas.

Spectro xepos by SPECTRO Analytical Instruments

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The SPECTRO Xepos is an advanced X-ray fluorescence (XRF) spectrometer designed for elemental analysis. It provides precise and accurate measurement of a wide range of elements in various sample types. The SPECTRO Xepos utilizes state-of-the-art technology to deliver reliable and efficient results for analytical needs.

Deuterated chloroform by Merck Group

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Deuterated chloroform is a chemical compound that consists of a single carbon atom, a single chlorine atom, and three deuterium atoms. It is a colorless, dense liquid with a characteristic chloroform-like odor. Deuterated chloroform is commonly used as a solvent in nuclear magnetic resonance (NMR) spectroscopy due to its specific chemical and physical properties.

Acetonitrile by Merck Group

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Acetonitrile is a colorless, volatile, flammable liquid. It is a commonly used solvent in various analytical and chemical applications, including liquid chromatography, gas chromatography, and other laboratory procedures. Acetonitrile is known for its high polarity and ability to dissolve a wide range of organic compounds.

What are some common applications of Methanesulfonyl chloride?

How can Methanesulfonyl chloride be used in pharmaceutical development?

Are there any safety precautions to consider when working with Methanesulfonyl chloride?

How can PubCompare.ai help streamline Methanesulfonyl chloride research?

PubCompare.ai's AI-driven platfrom can greatly assist researchers working with Methanesulfonyl chloride. The platfrom allows you to efficiently screen protocol literature, leveraging AI to pinpoint critical insights. This helps researchers identify the most effective protocols related to Methanesulfonyl chloride for their specific research goals. The platfrom's analysis can highlight key differences in protocol effectiveness, enabling you to choose the best option for reproducibility and accuracy.

Are there any variations or types of Methanesulfonyl chloride?

Yes, there are different variations of Methanesulfonyl chloride that may be used for specific applications. For example, deuterated or isotopically labeled versions of Methanesulfonyl chloride can be used for tracer studies or analytical purposes. Additionally, there may be different purities or grades of Methanesulfonyl chloride available depending on the intended use.

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mesyl chloride, sulfonylating agent, sulfonate groups, organic synthesis, pharmaceutical intermediates, polymers, chemical products, PubCompare.ai, AI-driven platform, protocols, literature, preprints, patents, Millex-LCR, Prep-HPLC, P4250, Triethylamine, Sodium azide, Hydrochloric acid, SPECTRO Xepos, Deuterated chloroform, Acetonitrile