2-amino-4-chloro-5-methylbenzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-chloro-2-cyano-4-methylaniline (4.0 g,0.024 mol), 30% aqueous KOH solution (56 ml), and 30% hydrogen peroxide (4 ml) was placed in an oil bath preheated to 130° C., then stirred at this temperature for 2 hours (a clear solution had obtained after 1.5 h). The clear solution was then allowed to cool to room temperature, diluted with water (200 ml), and acidified to pH ˜5.50 with 3N HCl, then allowed to stand at room temperature for few hours. The off white solid was collected by filtration, washed with water and dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C. 1H-NMR (DMSO-d6) 2.16 (s, 3H, CH3), 6.83, 7.62 (2×s, 2H, 3-H, 6-H), 8.50 (br s, 2H, NH2); MS (FAB, m/z): 188, 186 (M+H)+; FAB-HRMS: measured: 185.0256; calculated for C8H8ClNO2 (M+) 185.0244. was placed in an oil bath preheated to 130° C. had obtained after 1.5 h) to stand at room temperature for few hours The off white solid was collected by filtration washed with water dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-bromo-5-chloro-4-methylaniline (13.0 g 58.96 mmol) in N-methylpyrrolidinone (100 ml) was added copper(I) cyanide (10.56 g, 118 mmol). The reaction mixture was placed in an oil bath preheated to 163° C. and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to room temperature and then poured in ice-water (300 ml) and aqueous ammonia (90 ml). The brown precipitate was collected by filtration, washed with water (150 ml), dissolved in dichloromethane and the insoluble material was removed by filtration. The filtrate was washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo. Purification, on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%), afforded a white solid (6.52 g), mp 180° C.; 1H-NMR (DMSO-d6) 2.14 (s, 3H, 4-CH3), 6.11 (s, 2H, NH2), 6.86 (s, 1H, 6-H), 7.39 (s, 1H, 3-H); MS (FAB, m/z) 166,168 [(M+H)+; 90%, 40% respectively; Cl isotopic pattern]; FAB-HRMS: measured 166.0307; calculated for C8H8ClN2 (M+H)+ 166.0298. The reaction mixture was placed in an oil bath preheated to 163° C. The brown precipitate was collected by filtration washed with water (150 ml) dissolved in dichloromethane the insoluble material was removed by filtration The filtrate was washed with brine (100 ml) dried (MgSO4) concentrated in vacuo Purification on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-chloro-2-cyano-4-methylaniline (4.0 g,0.024 mol), 30% aqueous KOH solution (56 ml), and 30% hydrogen peroxide (4 ml) was placed in an oil bath preheated to 130° C., then stirred at this temperature for 2 hours (a clear solution had obtained after 1.5 h). The clear solution was then allowed to cool to room temperature, diluted with water (200 ml), and acidified to pH ˜5.50 with 3N HCl, then allowed to stand at room temperature for few hours. The off white solid was collected by filtration, washed with water and dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C. 1H-NMR (DMSO-d6) 2.16 (s, 3H, CH3), 6.83, 7.62 (2×s, 2H, 3-H, 6-H), 8.50 (br s, 2H, NH2); MS (FAB, m/z): 188, 186 (M+H)+; FAB-HRMS: measured: 185.0256; calculated for C8H8ClNO2 (M+) 185.0244. was placed in an oil bath preheated to 130° C. had obtained after 1.5 h) to stand at room temperature for few hours The off white solid was collected by filtration washed with water dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-bromo-5-chloro-4-methylaniline (13.0 g 58.96 mmol) in N-methylpyrrolidinone (100 ml) was added copper(I) cyanide (10.56 g, 118 mmol). The reaction mixture was placed in an oil bath preheated to 163° C. and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to room temperature and then poured in ice-water (300 ml) and aqueous ammonia (90 ml). The brown precipitate was collected by filtration, washed with water (150 ml), dissolved in dichloromethane and the insoluble material was removed by filtration. The filtrate was washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo. Purification, on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%), afforded a white solid (6.52 g), mp 180° C.; 1H-NMR (DMSO-d6) 2.14 (s, 3H, 4-CH3), 6.11 (s, 2H, NH2), 6.86 (s, 1H, 6-H), 7.39 (s, 1H, 3-H); MS (FAB, m/z) 166,168 [(M+H)+; 90%, 40% respectively; Cl isotopic pattern]; FAB-HRMS: measured 166.0307; calculated for C8H8ClN2 (M+H)+ 166.0298. The reaction mixture was placed in an oil bath preheated to 163° C. The brown precipitate was collected by filtration washed with water (150 ml) dissolved in dichloromethane the insoluble material was removed by filtration The filtrate was washed with brine (100 ml) dried (MgSO4) concentrated in vacuo Purification on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-chloro-2-cyano-4-methylaniline (4.0 g,0.024 mol), 30% aqueous KOH solution (56 ml), and 30% hydrogen peroxide (4 ml) was placed in an oil bath preheated to 130° C., then stirred at this temperature for 2 hours (a clear solution had obtained after 1.5 h). The clear solution was then allowed to cool to room temperature, diluted with water (200 ml), and acidified to pH ˜5.50 with 3N HCl, then allowed to stand at room temperature for few hours. The off white solid was collected by filtration, washed with water and dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C. 1H-NMR (DMSO-d6) 2.16 (s, 3H, CH3), 6.83, 7.62 (2×s, 2H, 3-H, 6-H), 8.50 (br s, 2H, NH2); MS (FAB, m/z): 188, 186 (M+H)+; FAB-HRMS: measured: 185.0256; calculated for C8H8ClNO2 (M+) 185.0244. was placed in an oil bath preheated to 130° C. had obtained after 1.5 h) to stand at room temperature for few hours The off white solid was collected by filtration washed with water dried in vacuo over P2O5 (4.13 g, 93%), mp 212-215° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-bromo-5-chloro-4-methylaniline (13.0 g 58.96 mmol) in N-methylpyrrolidinone (100 ml) was added copper(I) cyanide (10.56 g, 118 mmol). The reaction mixture was placed in an oil bath preheated to 163° C. and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to room temperature and then poured in ice-water (300 ml) and aqueous ammonia (90 ml). The brown precipitate was collected by filtration, washed with water (150 ml), dissolved in dichloromethane and the insoluble material was removed by filtration. The filtrate was washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo. Purification, on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%), afforded a white solid (6.52 g), mp 180° C.; 1H-NMR (DMSO-d6) 2.14 (s, 3H, 4-CH3), 6.11 (s, 2H, NH2), 6.86 (s, 1H, 6-H), 7.39 (s, 1H, 3-H); MS (FAB, m/z) 166,168 [(M+H)+; 90%, 40% respectively; Cl isotopic pattern]; FAB-HRMS: measured 166.0307; calculated for C8H8ClN2 (M+H)+ 166.0298. The reaction mixture was placed in an oil bath preheated to 163° C. The brown precipitate was collected by filtration washed with water (150 ml) dissolved in dichloromethane the insoluble material was removed by filtration The filtrate was washed with brine (100 ml) dried (MgSO4) concentrated in vacuo Purification on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%)