ethyl 3-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate

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: 3-Amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester (3.1 g, 11.1 mmol) was dissolved in dimethylformamide (50 mL) and treated with NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol). The reaction mixture was stirred at room temperature for 1 hour, dibromoethane (8.3 g, 3.8 mL, 44.2 mmol) was then added, and the mixture stirred for further 1 hour at room temperature. K2CO3 (6.11 g, 44.2 mmol) was added and the reaction mixture was stirred at 70° C. for 17 hours. A further aliquot of NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol) was added and, 3 hours later, a further aliquot of dibromoethane (2.1 g, 11.1 mmol). Stirring was continued at 70° C. for 18 hours. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography, yielding 3,4-dihydro-2H-quinoxaline-1,6-dicarboxylic acid 1-tert-butyl ester 6-ethyl ester as a light yellow solid, 1.0 g (29%), MS (ISP): m/e=307.3 (M+H+.); δH (300 MHz; CDCl3) 7.58 (1H, d), 7.34 (1H, d), 7.25 (1H, s), 4.33 (2H, q), 4.09 (1H, bs), 3.79 (2H, m), 3.43 (2H, m), 1.53 (9H, s), 1.37 (3H, t). the mixture stirred for further 1 hour at room temperature the reaction mixture was stirred at 70° C. for 17 hours Stirring was continued at 70° C. for 18 hours the mixture was extracted three times with dichloromethane The combined organic phases were dried over sodium sulfate evaporated The residue was purified by flash chromatography

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

実験手順: 3-Amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester (3.1 g, 11.1 mmol) was dissolved in dimethylformamide (50 mL) and treated with NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol). The reaction mixture was stirred at room temperature for 1 hour, dibromoethane (8.3 g, 3.8 mL, 44.2 mmol) was then added, and the mixture stirred for further 1 hour at room temperature. K2CO3 (6.11 g, 44.2 mmol) was added and the reaction mixture was stirred at 70° C. for 17 hours. A further aliquot of NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol) was added and, 3 hours later, a further aliquot of dibromoethane (2.1 g, 11.1 mmol). Stirring was continued at 70° C. for 18 hours. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography, yielding 3,4-dihydro-2H-quinoxaline-1,6-dicarboxylic acid 1-tert-butyl ester 6-ethyl ester as a light yellow solid, 1.0 g (29%), MS (ISP): m/e=307.3 (M+H+.); δH (300 MHz; CDCl3) 7.58 (1H, d), 7.34 (1H, d), 7.25 (1H, s), 4.33 (2H, q), 4.09 (1H, bs), 3.79 (2H, m), 3.43 (2H, m), 1.53 (9H, s), 1.37 (3H, t). the mixture stirred for further 1 hour at room temperature the reaction mixture was stirred at 70° C. for 17 hours Stirring was continued at 70° C. for 18 hours the mixture was extracted three times with dichloromethane The combined organic phases were dried over sodium sulfate evaporated The residue was purified by flash chromatography

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

実験手順: 4-Tert-butoxycarbonylamino-3-nitro-benzoic acid ethyl ester (3.5 g, 11.3 mmol) was dissolved in ethanol (300 mL) and 10% palladium on carbon was added (0.45 g, 0.42 mmol). The mixture was evacuated and filled with hydrogen, then stirred at room temperature for 1 hour. The catalyst was filtered, washing with ethanol, and the solvent was evaporated. The crude 3-amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester thus obtained [3.1 g, 95%, MS (ISP): m/e=279.3 (M−H)] was used as such in the following reaction. The mixture was evacuated filled with hydrogen The catalyst was filtered washing with ethanol the solvent was evaporated

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: 3-Amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester (3.1 g, 11.1 mmol) was dissolved in dimethylformamide (50 mL) and treated with NaH (−55% dispersion in oil) (0.3 g, 12.2 mmol). The reaction mixture was stirred at room temperature for 1 hour, dibromoethane (8.3 g, 3.8 mL, 44.2 mmol) was then added, and the mixture stirred for further 1 hour at room temperature. K2CO3 (6.11 g, 44.2 mmol) was added and the reaction mixture was stirred at 70° C. for 17 hours. A further aliquot of NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol) was added and, 3 hours later, a further aliquot of dibromoethane (2.1 g, 11.1 mmol). Stirring was continued at 70° C. for 18 hours. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography, yielding 3,4-dihydro-2H-quinoxaline-1,6-dicarboxylic acid 1-tert-butyl ester 6-ethyl ester as a light yellow solid, 1.0 g (29%), MS (ISP): m/e=307.3 (M+H+.); δH (300 MHz; CDCl3) 7.58 (1H, d), 7.34 (1H, d), 7.25 (1H, s), 4.33 (2H, q), 4.09 (1H, bs), 3.79 (2H, m), 3.43 (2H, m), 1.53 (9H, s), 1.37 (3H, t). the mixture stirred for further 1 hour at room temperature the reaction mixture was stirred at 70° C. for 17 hours Stirring was continued at 70° C. for 18 hours the mixture was extracted three times with dichloromethane The combined organic phases were dried over sodium sulfate evaporated The residue was purified by flash chromatography

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

実験手順: 4-Tert-butoxycarbonylamino-3-nitro-benzoic acid ethyl ester (3.5 g, 11.3 mmol) was dissolved in ethanol (300 mL) and 10% palladium on carbon was added (0.45 g, 0.42 mmol). The mixture was evacuated and filled with hydrogen, then stirred at room temperature for 1 hour. The catalyst was filtered, washing with ethanol, and the solvent was evaporated. The crude 3-amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester thus obtained [3.1 g, 95%, MS (ISP): m/e=279.3 (M−H)] was used as such in the following reaction. The mixture was evacuated filled with hydrogen The catalyst was filtered washing with ethanol the solvent was evaporated

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

実験手順: 3-Amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester (3.1 g, 11.1 mmol) was dissolved in dimethylformamide (50 mL) and treated with NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol). The reaction mixture was stirred at room temperature for 1 hour, dibromoethane (8.3 g, 3.8 mL, 44.2 mmol) was then added, and the mixture stirred for further 1 hour at room temperature. K2CO3 (6.11 g, 44.2 mmol) was added and the reaction mixture was stirred at 70° C. for 17 hours. A further aliquot of NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol) was added and, 3 hours later, a further aliquot of dibromoethane (2.1 g, 11.1 mmol). Stirring was continued at 70° C. for 18 hours. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography, yielding 3,4-dihydro-2H-quinoxaline-1,6-dicarboxylic acid 1-tert-butyl ester 6-ethyl ester as a light yellow solid, 1.0 g (29%), MS (ISP): m/e=307.3 (M+H+); δH (300 MHz; CDCl3) 7.58 (1H, d), 7.34 (1H, d), 7.25 (1H, s), 4.33 (2H, q), 4.09 (1H, bs), 3.79 (2H, m), 3.43 (2H, m), 1.53 (9H, s), 1.37 (3H, t). the mixture stirred for further 1 hour at room temperature the reaction mixture was stirred at 70° C. for 17 hours Stirring was continued at 70° C. for 18 hours the mixture was extracted three times with dichloromethane The combined organic phases were dried over sodium sulfate evaporated The residue was purified by flash chromatography

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

実験手順: 4-Tert-butoxycarbonylamino-3-nitro-benzoic acid ethyl ester (3.5 g, 11.3 mmol) was dissolved in ethanol (300 mL) and 10% palladium on carbon was added (0.45 g, 0.42 mmol). The mixture was evacuated and filled with hydrogen, then stirred at room temperature for 1 hour. The catalyst was filtered, washing with ethanol, and the solvent was evaporated. The crude 3-amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester thus obtained [3.1 g, 95%, MS (ISP): m/e=279.3 (M−H)] was used as such in the following reaction. The mixture was evacuated filled with hydrogen The catalyst was filtered washing with ethanol the solvent was evaporated

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

実験手順: 3-Amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester (3.1 g, 11.1 mmol) was dissolved in dimethylformamide (50 mL) and treated with NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol). The reaction mixture was stirred at room temperature for 1 hour, dibromoethane (8.3 g, 3.8 mL, 44.2 mmol) was then added, and the mixture stirred for further 1 hour at room temperature. K2CO3 (6.11 g, 44.2 mmol) was added and the reaction mixture was stirred at 70° C. for 17 hours. A further aliquot of NaH (˜55% dispersion in oil) (0.3 g, 12.2 mmol) was added and, 3 hours later, a further aliquot of dibromoethane (2.1 g, 11.1 mmol). Stirring was continued at 70° C. for 18 hours. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography, yielding 3,4-dihydro-2H-quinoxaline-1,6-dicarboxylic acid 1-tert-butyl ester 6-ethyl ester as a light yellow solid, 1.0 g (29%), MS (ISP): m/e=307.3 (M+H+.); δH (300 MHz; CDCl3) 7.58 (1H, d), 7.34 (1H, d), 7.25 (1H, s), 4.33 (2H, q), 4.09 (1H, bs), 3.79 (2H, m), 3.43 (2H, m), 1.53 (9H, s), 1.37 (3H, t). the mixture stirred for further 1 hour at room temperature the reaction mixture was stirred at 70° C. for 17 hours Stirring was continued at 70° C. for 18 hours the mixture was extracted three times with dichloromethane The combined organic phases were dried over sodium sulfate evaporated The residue was purified by flash chromatography

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

実験手順: 4-Tert-butoxycarbonylamino-3-nitro-benzoic acid ethyl ester (3.5 g, 11.3 mmol) was dissolved in ethanol (300 mL) and 10% palladium on carbon was added (0.45 g, 0.42 mmol). The mixture was evacuated and filled with hydrogen, then stirred at room temperature for 1 hour. The catalyst was filtered, washing with ethanol, and the solvent was evaporated. The crude 3-amino-4-tert-butoxycarbonylamino-benzoic acid ethyl ester thus obtained [3.1 g, 95%, MS (ISP): m/e=279.3 (M−H)] was used as such in the following reaction. The mixture was evacuated filled with hydrogen The catalyst was filtered washing with ethanol the solvent was evaporated