反应详情

Methyl 5-amino-2-methylbenzoate (223 mg) was dissolved in tetrahydrofuran (30 ml), under ice-cooling triphosgene (135 mg) was added, triethylamine (116 μl) was added thereto five times every 3 minutes, the mixture was stirred for 10 minutes at same temperature. Subsequently, a solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (500 mg) in tetrahydrofuran (20 ml) was added dropwise, stirred for 30 minutes at same temperature, and then stirred for 3 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water (50 ml) was added, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography(chloroform:ethyl acetate=10:1), to thereby obtain 271 mg of the titled compound.

1. additionwas added
2. stirringstirred for 30 minutes at same temperature
3. stirringstirred for 3 hours at room temperature
4. concentrationThe reaction mixture was concentrated under reduced pressure, water (50 ml)
5. additionwas added
6. extractionextracted with methylene chloride
7. washThe organic layer was washed with saturated brine
8. dry with materialdried over anhydrous sodium sulfate
9. customthe solvent was evaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography(chloroform:ethyl acetate=10:1)