4,4-dimethyl-3,5-dihydro-1H-1,5-benzodiazepin-2-one

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4,4-dimethyl-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.0 g) in N,N-dimethylaniline (20 ml) was added 4-nitrobenzoyl chloride (0.98 g) at ambient temperature. The mixture was stirred at 150° C. for 9 hours. The resulting mixture was diluted with chloroform and the organic layer was washed successively with 1N hydrochloric acid and saturated aqueous sodium bicarbonate. Drying, filtering and the removal of solvents afforded a crude product. The crude product was chromatographed on silica gel (1% methanol in chloroform) to give 4,4-dimethyl-5-(4-nitrobenzoyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (195 mg) as a slightly yellow solid. the organic layer was washed successively with 1N hydrochloric acid and saturated aqueous sodium bicarbonate Drying filtering the removal of solvents afforded a crude product The crude product was chromatographed on silica gel (1% methanol in chloroform)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A disposable tube was charged with 4,4-dimethyl-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (697 mg, 3.66 mmol) in THF (20 mL). Lawesson's Reagent (815 mg, 2.015 mmol) was added, and the solution was stirred at 80° C. for 3 h. The solution was concentrated, partitioned between water and ethyl acetate, separated, dried with sodium sulfate, concentrated with celite, and purified by silica gel chromatography to yield 4,4-dimethyl-4,5-dihydro-1H-benzo[b][1,4]diazepine-2(3H)-thione as a yellow oily solid (0.60 g, 2.91 mmol, 79%). The solution was concentrated partitioned between water and ethyl acetate separated dried with sodium sulfate concentrated with celite purified by silica gel chromatography

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

実験手順: An round bottomed flask was charged with crude 3-(2-aminophenylamino)-3-methylbutanoic acid (2.19 g, 10.52 mmol), HOBT (1.932 g, 12.62 mmol), EDC (2.419 g, 12.62 mmol), and a stirbar. DMF (20 mL, 0.5 M) was added, and the solution was stirred at rt overnight. The solution was diluted with water, extracted three times with methylene chloride, dried with sodium sulfate, concentrated with celite, and purified by silica gel chromatography (eluting with hexanes/ethyl acetate/1% isopropanol) to yield 4,4-dimethyl-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one as a yellow amorphous solid (0.697 g, 3.66 mmol, 35%). extracted three times with methylene chloride dried with sodium sulfate concentrated with celite purified by silica gel chromatography (eluting with hexanes/ethyl acetate/1% isopropanol)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4,4-dimethyl-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (1.0 g) in N,N-dimethylaniline (20 ml) was added 4-nitrobenzoyl chloride (0.98 g) at ambient temperature. The mixture was stirred at 150° C. for 9 hours. The resulting mixture was diluted with chloroform and the organic layer was washed successively with 1N hydrochloric acid and saturated aqueous sodium bicarbonate. Drying, filtering and the removal of solvents afforded a crude product. The crude product was chromatographed on silica gel (1% methanol in chloroform) to give 4,4-dimethyl-5-(4-nitrobenzoyl)-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (195 mg) as a slightly yellow solid. the organic layer was washed successively with 1N hydrochloric acid and saturated aqueous sodium bicarbonate Drying filtering the removal of solvents afforded a crude product The crude product was chromatographed on silica gel (1% methanol in chloroform)