Protocol full text hidden due to copyright restrictions
Open the protocol to access the free full text link
>
Chemicals & Drugs
>
Organic Chemical
>
Cyclopropanecarboxamide
Cyclopropanecarboxamide
Cyclopropanecarboxamide is a cyclic organic compound with a three-membered ring containing a carbonyl group and an amine substituent.
It is used in various chemical syntheses and has potential applications in medicinal chemistry and materials science.
PubCompare.ai's AI-driven platform can help optimize your Cyclopropanecarboxamide research by providing access to the best protocols from literature, pre-prints, and patents using intelligent comparison tools.
Streamline your process and find the optimal solution for your needs, experincing the power of AI-assisted research today.
It is used in various chemical syntheses and has potential applications in medicinal chemistry and materials science.
PubCompare.ai's AI-driven platform can help optimize your Cyclopropanecarboxamide research by providing access to the best protocols from literature, pre-prints, and patents using intelligent comparison tools.
Streamline your process and find the optimal solution for your needs, experincing the power of AI-assisted research today.
Most cited protocols related to «Cyclopropanecarboxamide»
1H NMR
Carbon-13 Magnetic Resonance Spectroscopy
Chlorides
cyclopropanecarboxamide
High-Performance Liquid Chromatographies
Indazoles
Methanol
Pressure
pyridine
Solvents
Step 1. To a solution of tert-butyl(3-aminophenyl)carbamate 4 (1 g, 4.80 mmol) in N,N-dimethylformamide (11.08 mL) were added
1-hydroxycyclopropanecarboxylic acid (0.588 g, 5.76 mmol), propylphosphonic
anhydride solution (T3P, 50% solution in ethyl acetate), (5.5 g, 5.046
mmol), and N,N-diisopropylethylamine
(2.17 g, 2.92 mL, 168 mmol). The reaction mixture was stirred at room
temperature for 66 h. After filtration, the filtrate was purified
by HPLC (water, HCOOH/acetonitrile (0.1%)) yielding the desired product tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate5 (0.17 g, 9.9%, 81% pure). Step 2. To a solution of tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate 5 (0.17 g, 0.471 mmol, 81% pure) in dioxane (1 mL) was added
a solution of HCl in dioxane (4 M, 0.94 mL). The reaction mixture
was stirred at room temperature overnight. Due to an incomplete reaction,
additional HCl in dioxane (4 M) was added (0.5 mL). Stirring was continued
at room temperature for 2 h. The precipitate was filtered, washed
with dioxane, and dried at room temperature yielding N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide hydrochloride6 (0.125 g, >100%). Step 3. To a solution of 7-nitrodibenzo[b,d]furan-2-sulfonyl chloride (0.06 g,
0.192 mmol) in N,N-dimethylformamide
(1 mL) were added triethylamine (0.058 mg, 0.08 mL, 0.577 mmol), dimethylaminopyridine
(2 mg, 0.019 mmol), and N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide
hydrochloride (0.073 g, 0.289 mmol, 90%). The reaction mixture was
stirred at room temperature overnight. The reaction mixture was treated
with N,N-dimethylformamide and water
(1 mL each), filtered, and finally purified by HPLC (water, HCOOH/acetonitrile
(0.1%)) yielding the desired compound 1-hydroxy-N-(3-{[(7-nitrodibenzo[b,d]furan-2-yl)sulfonyl]amino}phenyl)cyclopropanecarboxamide
(7 ) (45 mg, 47.5%). 1H NMR (400 MHz, DMSO-d6) δ [ppm] 0.86–0.96 (m, 2H), 1.07–1.17
(m, 2H), 6.43–6.56 (br, 1H), 6.79 (br d, J = 7.35 Hz, 1H), 7.10 (t, J = 8.11 Hz, 1H), 7.26
(d, J = 8.11 Hz, 1H), 7.80 (br, 1H), 7.97–8.10
(m, 2H), 8.35 (dd, J = 8.52, 1.52 Hz, 1H), 8.56 (d, J = 8.60 Hz, 1H), 8.71 (d, J = 1.57 Hz,
1H), 8.91 (br, 1H), 9.78 (br, 1H), 10.40 (br, 1H).
1-hydroxycyclopropanecarboxylic acid (0.588 g, 5.76 mmol), propylphosphonic
anhydride solution (T3P, 50% solution in ethyl acetate), (5.5 g, 5.046
mmol), and N,N-diisopropylethylamine
(2.17 g, 2.92 mL, 168 mmol). The reaction mixture was stirred at room
temperature for 66 h. After filtration, the filtrate was purified
by HPLC (water, HCOOH/acetonitrile (0.1%)) yielding the desired product tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate
a solution of HCl in dioxane (4 M, 0.94 mL). The reaction mixture
was stirred at room temperature overnight. Due to an incomplete reaction,
additional HCl in dioxane (4 M) was added (0.5 mL). Stirring was continued
at room temperature for 2 h. The precipitate was filtered, washed
with dioxane, and dried at room temperature yielding N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide hydrochloride
0.192 mmol) in N,N-dimethylformamide
(1 mL) were added triethylamine (0.058 mg, 0.08 mL, 0.577 mmol), dimethylaminopyridine
(2 mg, 0.019 mmol), and N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide
hydrochloride (0.073 g, 0.289 mmol, 90%). The reaction mixture was
stirred at room temperature overnight. The reaction mixture was treated
with N,N-dimethylformamide and water
(1 mL each), filtered, and finally purified by HPLC (water, HCOOH/acetonitrile
(0.1%)) yielding the desired compound 1-hydroxy-N-(3-{[(7-nitrodibenzo[b,d]furan-2-yl)sulfonyl]amino}phenyl)cyclopropanecarboxamide
(
(m, 2H), 6.43–6.56 (br, 1H), 6.79 (br d, J = 7.35 Hz, 1H), 7.10 (t, J = 8.11 Hz, 1H), 7.26
(d, J = 8.11 Hz, 1H), 7.80 (br, 1H), 7.97–8.10
(m, 2H), 8.35 (dd, J = 8.52, 1.52 Hz, 1H), 8.56 (d, J = 8.60 Hz, 1H), 8.71 (d, J = 1.57 Hz,
1H), 8.91 (br, 1H), 9.78 (br, 1H), 10.40 (br, 1H).
1H NMR
acetonitrile
Acids
Carbamates
cyclopropanecarboxamide
Dimethylformamide
dioxane
ethyl acetate
Filtration
furan
High-Performance Liquid Chromatographies
sulfonyl chloride
Sulfoxide, Dimethyl
TERT protein, human
triethylamine
Example 19
The procedure described in Example 1 was followed, using a DMF (2 ml) solution of 2-[4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid (racemic) (100 mg, 0.434 mmol) [Journal of Organic Chemistry (1997), 62(26), 9114-9122.], EDC (125 mg, 0.651 mmol), HOBt (74 mg, 0.477 mmol), triethylamine (0.18 ml) and the compound of Example 2D (115 mg, 0.434 mmol). The crude residue was applied to a silica gel chromatography column and eluted with a volume mixture of hexane and EtOAc (1/1) and isolated from MeOH to afford 20 mg (10% yield) of the title compound as white solids.
1H NMR (DMSOd-6, 300 MHz) δ ppm 1.32 (3H, d, J=7.3 Hz), 1.23-1.43 (2H, m), 1.99-2.05 (1H, m), 2.29 (3H, s), 2.28-2.39 (1H, m), 2.96 (3H, s), 4.85-4.96 (1H, m), 7.11-7.23 (3H, m), 7.36 (2H, d, J=8.1 Hz), 7.63 (2H, d, J=8.1 Hz), 8.56 (1H, d, J=8.1 Hz), 9.02 (1H, brs). MS (ESI): m/z 441 (M+H)+.
19b) N-((1R)-1-{3-Methyl-4-[(methylsulfonyl)amino]phenyl}ethyl)-2-[4-(trifluoromethyl)phenyl]cyclopropanecarboxamide (diastereomer Mixture)
Following Example 19a, the filtrate was evaporated under reduced pressure to give the title compound (80 mg, 42% yield) as the mixture of diastereomer products (1:2) as white solids.
1H NMR (300 MHz, DMSOd-6) δ 1.24-1.43 (5H, m), 1.99-2.05 (1H, m), 2.26-2.35 (4H, m), 2.94-2.96 (3H, m), 4.85-4.94 (1H, m), 7.09-7.23 (3H, m), 7.30-7.40 (2H, m), 7.57-7.64 (2H, m), 8.53-8.62 (1H, m), 8.99 (1H, brs). MS (ESI): m/z 441 (M+H)+.
Full text: Click here
Example 109
2-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (30 mg, 0.1 mmol) and 2-(methylsulfonyl)ethan-1-ol (13 mg, 0.1 mmol) were dissolved in DMF at room temperature. NaH 60% dispersion in mineral oil (9 mg, 0.21 mmol) was slowly added and then stirred for 24 h. Reaction mixture was diluted with EtOAc and washed with water. Organic layer was dried over MgSO4 and evaporated under reduced pressure. The crude product was purified via preparative HPLC (5-65% acetonitrile in water, 0.1% trifluoroacteic acid buffer) to yield N-(6-(3-cyano-4-hydroxyphenyl)pyrimidin-4-yl)cyclopropanecarboxamide. LCMS-ESI+ (m/z): [M+H]+ calcd for C15H12N4O2: 281.1; found: 281.1.
Full text: Click here
acetonitrile
Acids
benzonitrile
Buffers
cyclopropanecarboxamide
High-Performance Liquid Chromatographies
Lincomycin
Oil, Mineral
Pressure
Sulfate, Magnesium
Example 97
To a solution of N-(4-(3-cyano-4-fluorophenyl)pyridin-2-yl)cyclopropanecarboxamide (150 mg, 0.533 mmol) in 5 mL iPrOH was added RS)-3-methoxypyrrolidine (162 mg, 1.60 mmol) and DIEA (0.279 mL, 1.60 mmol) and stirred 140° C. in a microwave for 60 min. Purification by flash column chromatography gave (R)—N-(4-(3-cyano-4-(3-methoxypyrrolidin-1-yl)phenyl)pyridin-2-yl)cyclopropanecarboxamide (80 mg, 41% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.31-8.24 (m, 1H), 8.17 (d, J=1.7 Hz, 1H), 7.91 (d, J=2.4 Hz, 1H), 7.79 (dd, J=9.1, 2.4 Hz, 1H), 7.50 (dd, J=5.7, 1.8 Hz, 1H), 6.90 (d, J=9.2 Hz, 1H), 4.09 (td, J=4.4, 2.1 Hz, 1H), 3.77 (dd, J=11.2, 4.5 Hz, 1H), 3.67-3.57 (m, 3H), 3.26 (s, 3H), 2.16-2.01 (m, 1H), 2.05-1.94 (m, 2H), 0.89-0.79 (m, 4H). ES/MS 363.24 (M+H+).
Full text: Click here
1H NMR
Chromatography
cyclopropanecarboxamide
Microwaves
N,N-diisopropylethylamine
Sulfoxide, Dimethyl
Most recents protocols related to «Cyclopropanecarboxamide»
Example 35
A mixture of 6-chloro-4-((2-methoxy-5-(methoxymethyl)-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (25 mg, 0.059 mmol), cyclopropanecarboxamide (25.3 mg, 0.297 mmol), Pd2(dba)3, chloroform adduct (6.14 mg, 5.94 μmol), xantphos (6.87 mg, 0.012 mmol) and Cs2CO3 (77 mg, 0.238 mmol) in dioxane (0.5 mL) was degassed by bubbling N2 through the mixture for 5 minutes. The reaction vessel was sealed and heated to 130° C. for 30 minutes. The reaction mixture was diluted with DMSO, filtered and purified by prep. HPLC. The purfractions were concentrated to afford 6-(cyclopropane-carboxamido)-4-((2-methoxy-5-(methoxymethyl)-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (16.3 mg; 57.7%). MS (M+1) m/z: 470.0 (M+H)+. LC retention time 1.46 [I]. 1H NMR (500 MHz, DMSO-d6) δ 11.29 (s, 1H), 10.95 (s, 1H), 9.13 (s, 1H), 8.10 (d, J=9.0 Hz, 2H), 7.67 (d, J=1.8 Hz, 1H), 7.39 (d, J=1.7 Hz, 1H), 4.42 (s, 2H), 4.23 (s, 3H), 3.64 (s, 3H), 3.30 (s, 3H), 2.14-2.00 (m, 1H), 0.87-0.73 (m, 4H).
Full text: Click here
1H NMR
Blood Vessel
Chloroform
cyclopropane
cyclopropanecarboxamide
dioxane
High-Performance Liquid Chromatographies
pyridazine
Retention (Psychology)
Sulfoxide, Dimethyl
xantphos
Example 10
Ethyl 1-(4-benzylpiperazin-1-yl)cyclopropanecarboxylate. Ethyl 1-aminocyclopropanecarboxylate hydrochloride (0.500 g, 3.02 mmol, 1 eq) was added to a stirred mixture of N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (0.886 g, 3.30 mmol, 1.09 eq), EtOH (6.66 mL, 0.453 molar) and DIEA (5.30 mL, 30.3 mmol, 10.05 eq). The reaction mixture was stirred for 18 h at 78° C., then concentrated under reduced pressure. The crude material was partitioned between DCM and water. The layers were separated, and the aqueous layer was extracted with DCM. The combined organic extracts were concentrated under reduced pressure and the crude material was purified by silica gel column chromatography (5-10% EtOAc in hexanes) to give ethyl 1-(4-benzylpiperazin-1-yl)cyclopropanecarboxylate (0.409 g, 1.42 mmol, 47.0% yield) as a yellow oil. MS (ESI) m/z 289.2 [M+1]+.
Ethyl 1-(piperazin-1-yl)cyclopropanecarboxylate hydrochloride. To a solution of ethyl 1-(4-benzylpiperazin-1-yl)cyclopropanecarboxylate (0.200 g, 0.694 mmol, 1 eq) in anhydrous DCM (1.692 mL, 0.410 molar) cooled to 0° C., 1-chloroethyl carbonochloridate (0.110 mL, 1.02 mmol, 1.465 eq) was slowly added to maintain the temperature below 0° C. The mixture was stirred at 18° C. for 1 h. The reaction was concentrated to dryness and the residue was dissolved in EtOH (1.69 mL, 0.410 M). The resulting solution was stirred at 78° C. for 18 h. The reaction mixture was concentrated to dryness. The residue was then stirred in a 5:1 mixture of EtOH and MTBE, and the precipitate was collected by filtration to give ethyl 1-(piperazin-1-yl)cyclopropanecarboxylate hydrochloride (0.107 g, 0.456 mmol, 65.7% yield) as a beige solid. MS (ESI) m/z 199.2 [M+1]+.
2-((3-Bromo-4-hydroxyphenyl)amino)-2-methylpropanenitrile. To a solution of 4-amino-2-bromophenol (5.00 g, 26.6 mmol) in DCM (177 mL) and acetone (89 mL) were added trimethylsilyl cyanide (4.66 mL, 37.2 mmol) and trimethylsilyl trifluoromethylsulphonate (0.241 mL, 1.33 mmol). The reaction mixture was stirred at room temperature for 1 h, then was concentrated to remove the solvent. The crude material was purified by silica gel column chromatography (0-100% EtOAc in hexanes) to afford 2-((3-bromo-4-hydroxyphenyl)amino)-2-methylpropanenitrile (4.56 g, 17.87 mmol, 67.2% yield) as a brown solid. MS (ESI) m/z 256.2 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.55-9.66 (m, 1H), 7.05 (d, J=2.69 Hz, 1H), 6.83-6.87 (m, 1H), 6.77-6.81 (m, 1H), 5.51 (s, 1H), 1.55 (s, 6H).
4-(3-(3-Bromo-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile. 2-((3-Bromo-4-hydroxyphenyl)amino)-2-methylpropanenitrile (1.00 g, 3.92 mmol) and 4-isothiocyanato-2-(trifluoromethyl)benzonitrile (0.894 g, 3.92 mmol) were combined in DMA (13.07 mL) and stirred at room temperature overnight. MeOH (5 mL) and a 3.0 N aqueous solution of HCl (5 mL) were added and the reaction was heated at 70° C. After 2 h, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc before the combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (0-100% EtOAc in hexanes) to afford 4-(3-(3-bromo-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (1.23 g, 2.423 mmol, 62.0% yield) as a white solid. MS (ESI) m/z 484.0 [M+1]+.
2-Bromo-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenyl acetate. A solution of 4-(3-(3-bromo-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (0.75 g, 1.55 mmol) in DCM (7.74 mL) treated with DIEA (0.541 mL, 3.10 mmol) and acetyl chloride (0.132 mL, 1.86 mmol) was stirred at room temperature. After 12 h, the reaction was diluted with EtOAc (100 mL) and the organic layer was washed with a saturated aqueous solution of sodium bicarbonate (2×100 mL) and brine (100 mL). The organic layer was dried over magnesium sulfate and concentrated to provide a colorless oil which was purified by silica gel column chromatography (20-50% EtOAc in hexanes) to give the title compound (0.766 g, 1.455 mmol, 94% yield). MS (ESI) m/z 526.0 [M+1]+; 1H NMR (400 MHz, CDCl3) δ ppm 7.97 (s, 1H), 7.94 (s, 1H), 7.82 (dd, J=2.1, 8.2 Hz, 1H), 7.58 (d, J=2.3 Hz, 1H), 7.36-7.27 (m, 2H), 2.40 (s, 3H), 1.61 (s, 6H).
4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl acetate. To a mixture of 2-bromo-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenyl acetate (2 g, 3.80 mmol), [(2-dicyclohexylphosphino-2′,6′-bis(N,N-dimethylamino)-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate (0.311 g, 0.380 mmol) and 2-(2-dicyclohexylphosphanylphenyl)-N1,N1,N3,N3-tetramethyl-benzene-1,3-diamine (0.166 g, 0.38 mmol) combined in a schlenk flask and purged with argon, was added toluene (15.20 mL). The reaction mixture was placed in an ice bath for 5 min, then treated with a 0.5 M solution of ethylzinc(II) bromide in THE (6.08 mL, 3.04 mmol, 0.8 equiv). After 30 min, an additional 0.5 equivalent of ethylzinc(II) bromide solution was used (3.80 mL, 1.90 mmol) at 0° C. for 30 min, the reaction was quenched with the addition of a 2.0 M aqueous solution of HCl (2.470 mL, 4.94 mmol) and the mixture was diluted with EtOAc (350 mL). The organic layer was washed twice with a saturated aqueous solution of sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford a brown solid. The crude material was purified by silica gel column chromatography (0-45% EtOAc in hexanes) to afford 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl acetate (0.986 g, 2.07 mmol, 55.0% yield). MS(ESI) m/z 476 [M+1]+.
4-(3-(3-Ethyl-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile. A suspension of 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl acetate (0.876 g, 1.84 mmol) and potassium carbonate (0.255 g, 1.84 mmol) in MeOH (20 mL) was stirred at ambient temperature. After 40 min, the solution diluted with EtOAc (200 mL) and partitioned with water (50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the title compound (0.766 g, 1.76 mmol, 96.0% yield). MS(ESI) m/z 434 [M+1]+.
4-(3-(4-(2-Bromoethoxy)-3-ethylphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile. 1,2-Dibromoethane (2.99 mL, 34.6 mmol, 20.0 eq), cesium carbonate (1.97 g, 6.06 mmol, 3.5 eq) and 4-(3-(3-ethyl-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (0.750 g, 1.73 mmol, 1 eq) were dissolved in DMF (20.36 mL, 0.085 M) in a preheated flask, and the reaction was stirred at 60° C. for 18 h under a nitrogen atmosphere. The reaction was quenched with water and the mixture was diluted with EtOAc. The aqueous phase was extracted with EtOAc and the combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude residue was purified by silica gel column chromatography (0-100% EtOAc in hexane). Fractions were concentrated to a residue that was triturated with DCM and hexane to afford 4-(3-(4-(2-bromoethoxy)-3-ethylphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (0.296 g, 0.548 mmol, 31.7% yield) as a beige solid. MS (ESI) m/z 540.0 [M]+.
Ethyl 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxylate. To a solution of ethyl 1-(piperazin-1-yl)cyclopropanecarboxylate hydrochloride (0.107 g, 0.456 mmol, 1 eq) in DMF (4.56 mL, 0.1 molar) was added 4-(3-(4-(2-bromoethoxy)-3-ethylphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (0.296 g, 0.547 mmol, 1.2 eq) and DIEA (0.279 mL, 1.596 mmol, 3.5 eq). The vessel was sealed and the mixture was heated to 60° C. with stirring for 18 h. The reaction was concentrated and purified by silica gel column chromatography (0-10% MeOH in DCM) to give ethyl 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxylate (0.090 g, 0.137 mmol, 30.0% yield) as an orange oil. MS (ESI) m/z 658.2 [M+1]+.
(S)-2-(4-(2-(4-(3-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperidin-1-yl)propanoic acid tetrahydrochloride. To ethyl 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxylate (0.090 g, 0.137 mmol) was added a 6 M aqueous solution of HCl (1.140 mL, 6.84 mmol) slowly at 0° C. The reaction was gradually warmed to 100° C. and stirred for 18 h. The reaction mixture was concentrated to afford 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxylic acid, tetrahydrochloride (0.108 g, 0.139 mmol, 102% yield) as a pale yellow solid. MS (ESI) m/z 630.2 [M+1]+.
1-(4-(2-(4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)cyclopropanecarboxamide hydrochloride. 1-(4-(2-(4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxylic acid tetrahydrochloride (0.108 g, 0.139 mmol, 1 eq) was combined with 3-((3-aminophenyl)amino)piperidine-2,6-dione trifluoroacetate salt (0.046 g, 0.139 mmol, 1 eq), HATU (0.058 g, 0.153 mmol, 1.1 eq), DIEA (0.170 mL, 0.975 mmol, 7 eq) in DMF (0.696 mL, 0.2 molar), and the reaction was stirred at 25° C. for 15 min. The reaction was quenched with water and the mixture was diluted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic extracts were concentrated. The crude material was purified by standard methods to afford 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)cyclopropanecarboxamide hydrochloride (0.027 g, 0.032 mmol, 22.7% yield). MS (ESI) m/z 831.6 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 10.78 (s, 1H), 10.49 (br s, 1H), 9.48 (s, 1H), 8.39 (d, 1H, J=8.3 Hz), 8.29 (d, 1H, J=1.7 Hz), 8.07 (dd, 1H, J=1.7, 8.3 Hz), 7.1-7.2 (m, 4H), 7.02 (t, 1H, J=8.0 Hz), 6.79 (dd, 1H, J=1.0, 8.1 Hz), 6.43 (dd, 1H, J=1.7, 8.1 Hz), 4.49 (t, 2H, J=4.4 Hz), 4.30 (dd, 1H, J=4.8, 11.3 Hz), 3.58 (br s, 2H), 3.44 (t, 4H, J=10.6 Hz), 2.97 (br d, 2H, J=12.2 Hz), 2.7-2.9 (m, 3H), 2.66 (q, 2H, J=7.4 Hz), 2.59 (td, 1H, J=4.3, 17.2 Hz), 2.1-2.1 (m, 1H), 1.89 (dq, 1H, J=4.5, 12.2 Hz), 1.50 (s, 6H), 1.17 (t, 3H, J=7.5 Hz), 1.1-1.2 (m, 2H), 1.0-1.1 (m, 2H).
Full text: Click here
Example 33
A mixture of 6-chloro-4-((2-methoxy-4-methyl-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (20 mg, 0.051 mmol), cyclopropanecarboxamide (8.71 mg, 0.102 mmol), Pd2(dba)3, chloroform adduct (5.29 mg, 5.12 μmol), xantphos (5.92 mg, 10.23 μmol) and Cs2CO3 (66.7 mg, 0.205 mmol) in dioxane (0.5 mL) was degassed by bubbling N2 through the mixture for 5 minutes. The reaction vessel was sealed and heated to 130° C. for 45 minutes. The reaction mixture was diluted with DMF. The mixture was filtered through a 0.45 micron nylon filter and the filtrate was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm
particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Gradient: a 0-minute hold at 13% B, 13-53% B over 20 minutes, then a 0-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS signals. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 6-(cyclopropanecarboxamido)-4-((2-methoxy-4-methyl-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (8.4 mg, 37.4%). MS (M+1) m/z: 440.3 (M+H)+. LC retention time 1.48 [I]. 1H NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 10.79 (s, 1H), 9.09 (s, 1H), 8.08 (s, 1H), 7.86 (s, 1H), 7.39 (d, J=8.2 Hz, 1H), 7.16 (d, J=8.2 Hz, 1H), 4.22 (s, 3H), 3.41 (s, 3H), 2.19 (s, 3H), 2.12-2.04 (m, 1H), 0.87-0.77 (m, 4H).
Full text: Click here
Example 32
A mixture of methyl 3-((6-chloro-3-((methyl-d3)carbamoyl)pyridazin-4-yl)amino)-4-methoxy-5-(2-methyl-2H-1,2,3-triazol-4-yl)benzoate (95 mg, 0.218 mmol), cyclopropanecarboxamide (93 mg, 1.092 mmol), Pd2(dba)3, Chloroform adduct (22.57 mg, 0.022 mmol), xantphos (25.3 mg, 0.044 mmol) and Cs2CO3 (285 mg, 0.874 mmol) in dioxane (1.5 mL) was degassed by bubbling N2 through the mixture for 5 minutes. The reaction vessel was sealed and heated to 130° C. for 30 minutes. The reaction mixture was concentrated to dryness and the residue was suspended in water. The pH was adjusted to ˜2 with 1N HCl. The suspension was filtered and washed with water, followed by ethyl ether. Drying afforded a residue of 101 mg, of which 20 mg was dissolved in DMSO and was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with ammonium acetate; Gradient: a 0-minute hold at 11% B, 11-61% B over 20 minutes, then a 0-minute hold at 100% B; Flow Rate: 20 mL/min; Column. Temperature: 25 C. Fraction collection was triggered by MS signals. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford methyl 3-((6-(cyclopropanecarboxamido)-3-((methyl-d3)carbamoyl)-pyridazin-4-yl)amino)-4-methoxy-5-(2-methyl-2H-1,2,3-triazol-4-yl)benzoate (6.2 mg, 28.1% yield). MS (M+1) m/z: 484.1 (M+H)+. LC retention time 1.56 [I]. 1H NMR (500 MHz, DMSO-d6) δ 11.33 (br s, 1H), 11.06 (br s, 1H), 9.15 (br s, 1H), 8.32 (br s, 1H), 8.15 (s, 1H), 8.08 (br s, 1H), 7.99 (br s, 1H), 4.25 (br s, 3H), 3.86 (br s, 3H), 3.73 (br s, 3H), 2.06 (br d, J=1.2 Hz, 1H), 0.90-0.71 (m, 4H).
Full text: Click here
Example 1
To a solution of 6-chloro-4-((2-methoxy-3-(2-ethyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (101 mg, 0.26 mmol), cyclopropanecarboxamide (110 mg, 1.29 mmol) in dioxane (2.5 mL) and the reaction mixture was purged under N2 for 5 mins. To this solution was added xantphos (30 mg, 0.052 mmol), Pd2dba3 (24 mg, 0.026 mmol) and cesium carbonate (337 mg, 1.03 mmol) and the mixture was stirred at 130° C. for 45 minutes. After cooling to room temperature, the reaction mixture was purified using a 12 gm isco silica gel cartridge, eluted with a 0-10% MeOH/DCM gradient. The pure fractions were concentrated to afford 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(2-ethyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (79 mg, 66%) as an off white solid. MS (M+1) m/z: 440.2 [M+H]+, LC retention time 1.53 min [I]. 1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 11.01 (s, 1H), 9.16 (s, 1H), 8.14 (d, J=7.9 Hz, 2H), 7.72 (dd, J=7.9, 1.5 Hz, 1H), 7.47 (dd, J=8.0, 1.5 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 4.52 (q, J=7.3 Hz, 2H), 3.66 (s, 3H), 2.13-2.05 (m, 1H), 1.52 (t, J=7.3 Hz, 3H), 0.87-0.78 (m, 4H).
The following examples 2-8 were prepared in a similar manner to the preparation of Example 1.
Full text: Click here
Top products related to «Cyclopropanecarboxamide»
Sourced in United States, Germany
VX-661 is a laboratory product manufactured by Selleck Chemicals. It is a small molecule compound used for research purposes. The core function of VX-661 is to serve as a tool for scientific investigation and experimentation.
Sourced in United States, Germany
VX-809 is a chemical compound used as laboratory equipment. It serves as a core functional component in various scientific applications. The detailed specifications and intended use cases of VX-809 are not available at this time.
Sourced in United States
The MRL/Mp is a laboratory equipment product manufactured by Jackson ImmunoResearch. It is designed for use in research applications, but a detailed description of its core function cannot be provided while maintaining an unbiased and factual approach. Further information on the intended use of this product would require additional research to present accurately and without interpretation.
Sourced in United States
VX-770 is a laboratory instrument manufactured by Merck Group. It is designed for the analysis and measurement of various chemical and biological samples. The core function of VX-770 is to provide accurate and reliable data for research and testing purposes.
Sourced in United States, Germany, United Kingdom, China, Italy, Japan, Sao Tome and Principe, Canada, Macao, Poland, India, France, Spain, Portugal, Australia, Switzerland, Ireland, Belgium, Sweden, Israel, Brazil, Czechia, Denmark, Austria
Trypsin is a serine protease enzyme that is commonly used in cell biology and biochemistry laboratories. Its primary function is to facilitate the dissociation and disaggregation of adherent cells, allowing for the passive release of cells from a surface or substrate. Trypsin is widely utilized in various cell culture applications, such as subculturing and passaging of adherent cell lines.
Sourced in United States, Germany
Sorafenib is a small molecule kinase inhibitor. It functions by inhibiting multiple kinases involved in tumor cell signaling and angiogenesis.
Sourced in United States, Germany, France, Denmark, Sao Tome and Principe, Macao, United Kingdom, Japan, China
Isobutylmethylxanthine is a laboratory reagent used primarily as a phosphodiesterase inhibitor in cell culture and biochemical research applications. It is a synthetic compound that can modulate the activity of cyclic nucleotide signaling pathways. The core function of Isobutylmethylxanthine is to inhibit the breakdown of cyclic AMP and cyclic GMP, which can lead to increased levels of these important signaling molecules in cells.
Sourced in Germany, United States
Elexacaftor is a laboratory instrument designed for the analysis and purification of chemical compounds. It utilizes advanced chromatographic techniques to separate and isolate target molecules from complex mixtures. The core function of Elexacaftor is to provide researchers and scientists with a reliable and efficient tool for the purification and characterization of chemical samples.
Sourced in United States, Germany
VX-445 is a lab equipment product designed for use in analytical and research applications. It is a versatile instrument capable of performing various analytical tasks. The core function of VX-445 is to provide accurate and reliable data to support scientific investigations.
Sourced in United States, Germany, United Kingdom, France, Sao Tome and Principe, Canada, Italy, Japan, China, Switzerland, Macao, Australia
Forskolin is a lab equipment product manufactured by Merck Group. It is a compound derived from the roots of the Coleus forskohlii plant. Forskolin is used as a tool for research purposes in the laboratory setting.