2-溴-5-氯-4-甲基苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-acetamido-5-bromo-2-chlorotoluene (64 g, 0.245 mol) in glacial acetic acid (48 ml) and concentrated hydrochloric acid (96 ml) was heated at 118° C. for 24 h. The reaction mixture was allowed to cool to room temperature, diluted with water (200 ml), cooled in an ice-bath and the pH was. adjusted to 5 with a aqueous solution of NaOH (50% w/v). The precipitate was collected by filtration washed with water, and dried in vacuo over P2O5 to afford a white solid (50.7 g, 94%), mp 90° C. cooled in an ice-bath The precipitate was collected by filtration washed with water dried in vacuo over P2O5

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-acetamido-5-bromo-2-chlorotoluene (64 g, 0.245 mol) in glacial acetic acid (48 ml) and concentrated hydrochloric acid (96 ml) was heated at 118° C. for 24 h. The reaction mixture was allowed to cool to room temperature, diluted with water (200 ml), cooled in an ice-bath and the pH was. adjusted to 5 with a aqueous solution of NaOH (50% w/v). The precipitate was collected by filtration washed with water, and dried in vacuo over P2O5 to afford a white solid (50.7 g, 94%), mp 90° C. cooled in an ice-bath The precipitate was collected by filtration washed with water dried in vacuo over P2O5

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-acetamido-5-bromo-2-chlorotoluene (64 g, 0.245 mol) in glacial acetic acid (48 ml) and concentrated hydrochloric acid (96 ml) was heated at 118° C. for 24 h. The reaction mixture was allowed to cool to room temperature, diluted with water (200 ml), cooled in an ice-bath and the pH was. adjusted to 5 with a aqueous solution of NaOH (50% w/v). The precipitate was collected by filtration washed with water, and dried in vacuo over P2O5 to afford a white solid (50.7 g, 94%), mp 90° C. cooled in an ice-bath The precipitate was collected by filtration washed with water dried in vacuo over P2O5