反应详情

Diphenylphosphoryl azide (6.60 g) and triethylamine (3.75 g) were added to a solution of isophthalic acid benzyl ester (5.38 g) in anhydrous dioxane (50 ml), and the mixture was stirred at internal temperature 60° for 30 minutes and stirred at internal temperature 80° for one hour. The reaction mixture was allowed to cool at room temperature,a solution of (+)-1-(2-toluoylmethyl)-2-oxo-3-amino-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.0 g) in anhydrous dioxane (50 ml) was added thereto, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure, chloroform (200 ml) was added to the residue, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(NH-DM1020, produced by Fujisilicia Co. Ltd., n-hexane:ethyl acetate=2:1), to thereby obtain 4.08 g of the title compound (Yield 85.2%).

1. stirringstirred at internal temperature 80° for one hour
2. stirringthe mixture was stirred at room temperature for 15 minutes
3. concentrationThe reaction mixture was concentrated under reduced pressure, chloroform (200 ml)
4. additionwas added to the residue
5. washthe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was evaporated under reduced pressure
8. customthe residue was purified by silica gel column chromatography(NH-DM1020
9. customproduced by Fujisilicia Co