1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZEPIN-2-ONE

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: 2-Oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (1.95 g, 11.96 mmol) was reacted with ethyl iodide (1.4 ml, 17.5 mmol) according to the procedure in Example 18A. The product was purified by flash chromatography on silica (eluant EtOAc); yield 1.70 g (75%). The product was purified by flash chromatography on silica (eluant EtOAc)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one (2.0 g, 12.3 mmol) in DMF (30 ml), at −10° C., was added sodium hydride (0.54 g, 60% dispersion, 13.6 mmol). The mixture was stirred at −10° C. for 15 min, then methyl iodide (0.77 ml, 12.3 mmol) was added. The mixture was stirred at −100° C. for a further 1 h and then concentrated in vacuo. The residue was taken up in EtOAc and washed with brine (3 times), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc) to give a white solid; yield 1.70 g (78%). The mixture was stirred at −100° C. for a further 1 h concentrated in vacuo washed with brine (3 times) dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography on silica (eluant EtOAc) to give a white solid

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one (5.0 g, 30.8 mmol) in DMF (30 ml), at −10° C., was added sodium hydride (1.35 g, 60% dispersion, 33.9 mmol). The mixture was stirred at −10° C. for 15 min, then methyl bromoacetate (2.92 ml, 30.8 mmol) was added. The mixture was stirred at −10° C. for a further 1 h and then concentrated in vacuo. The residue was taken up in EtOAc and washed with brine (3 times), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc) to give a white solid; yield 7.08 g (98%). The mixture was stirred at −10° C. for a further 1 h concentrated in vacuo washed with brine (3 times) dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography on silica (eluant EtOAc) to give a white solid

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

実験手順: To an ice cold solution of lithium aluminium hydride (4.68 g, 123 mmol) in dry THF (100 ml), under a nitrogen atmosphere, was added dropwise a solution of 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one (5.0 g, 30.9 mmol) in dry THF (50 ml). The mixture was allowed to warm to room temperature and then heated at reflux for 2 h. The mixture was then cooled to 0° C. and a solution of aqueous ammonium hydroxide (10 ml) in THF (60 ml) was added dropwise. The resultant suspension was stirred for 1 h and then filtered through a pad of celite. The filtrate was evaporated in vacuo to give a tan solid; yield 4.36 g (95%). heated at reflux for 2 h The mixture was then cooled to 0° C. filtered through a pad of celite The filtrate was evaporated in vacuo to give a tan solid

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

実験手順: To a solution of 1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (700 mg) in pyridine (10 ml) was added 3,4-dimethoxybenzenesulfonyl chloride (1.07 g) and the mixture was stirred at ambient temperature for 2 hours. The resulting mixture was diluted with ethyl acetate, and then the organic solution was washed successively with 0.5N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine. Drying, filtering and the removal of solvents afforded a crude product. The crude product was triturated with a mixture of diethyl ether and n-hexane (1:1) to give 5-(3,4-dimethoxybenzenesulfonyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.33 g) as a yellow powder. the organic solution was washed successively with 0.5N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine Drying filtering the removal of solvents afforded a crude product The crude product was triturated with a mixture of diethyl ether and n-hexane (1:1)

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

実験手順: To a solution of 3-methoxy-4-nitrobenzoic acid (800 mg) and catalytic amount of N,N-dimethylformamide in dichloromethane (8 ml) was added oxalyl chloride (0.7 ml) at 0° C. and the solution was stirred at ambient temperature for 30 minutes followed by the removal of solvents to give a crude acid chloride. To a solution of 1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (658 mg) and triethylamine (821 mg) in dichloromethane (4 ml) was added a solution of the above acid chloride in dichloromethane (4 ml) at ambient temperature and the mixture was stirred at ambient temperature for 1 hour. The resultant mixture was filtered and the solid was washed with water and diethyl ether to give 5-(3-methoxy-4-nitrobenzoyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.29 g) as a colorless prisms. followed by the removal of solvents to give a crude acid chloride the mixture was stirred at ambient temperature for 1 hour The resultant mixture was filtered the solid was washed with water and diethyl ether

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

実験手順: To a solution of 3-methoxy-4-nitrobenzoic acid (800 mg) and catalytic amount of N,N-dimethylformamide in dichloromethane (8 ml) was added oxalyl chloride (0.7 ml) at 0° C. and the solution was stirred at ambient temperature for 30 minutes followed by the removal of solvents to give a crude acid chloride. To a solution of 1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (658 mg) and triethylamine (821 mg) in dichloromethane (4 ml) was added a solution of the above acid chloride in dichloromethane (4 ml) at ambient temperature and the mixture was stirred at ambient temperature for 1 hour. The resultant mixture was filtered and the solid was washed with water and diethyl ether to give 5-(3-methoxy-4-nitrobenzoyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.29 g) as a colorless prisms. followed by the removal of solvents to give a crude acid chloride the mixture was stirred at ambient temperature for 1 hour The resultant mixture was filtered the solid was washed with water and diethyl ether

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

実験手順: To a solution of 1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (0.87 g) and triethylamine (0.55 g) in dichloromethane (5 ml) was added a solution of 4-nitrobenzoyl chloride (1.00 g) in dichloromethane (5 ml) at ambient temperature. After being stirred at ambient temperature for 2 hours, the solution was washed successively with 0.5N hydrochloric acid, saturated sodium bicarbonate aqueous solution, and brine. The organic layer was dried over magnesium sulfate, filtered and the solvents was evaporated. Trituration with a mixture of diethyl ether and diisopropyl ether (1:1) of a crude product afforded 5-(4-nitrobenzoyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.60 g) as a slightly brown powder. the solution was washed successively with 0.5N hydrochloric acid, saturated sodium bicarbonate aqueous solution, and brine The organic layer was dried over magnesium sulfate filtered the solvents was evaporated Trituration with a mixture of diethyl ether and diisopropyl ether (1:1) of a crude product