反应详情

Triethylamine (70 μL, 0.50 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (70 mg, 0.167 mmol) and 4-nitrophenyl chloroformate (34 mg, 0.167 mmol) in tetrahydrofuran (2 mL) at 0° C. After 15 min, a solution of 1-methyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (31 mg, 0.167 mmol) in dichloromethane (2 mL) and triethylamine (93 μL, 0.67 mmol) were added and the mixture was allowed to warn to ambient temperature. After 4 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol) gave the title compound (33 mg). MS 555.2107 (M+1).

1. customto warn to ambient temperature
2. waitAfter 4 h
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol)