反应详情

Triethylamine (0.28 mL, 1.97 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 (275 mg, 0.66 mmol) and 4-nitrophenyl chloroformate (139 mg, 0.69 mmol) in tetrahydrofuran (2.5 mL) at 0° C. After 15 min, a solution of the acetate salt of 2,8-diazaspiro[4.5]decane-1,3-dione (WO 2004/076455) (180 mg, 0.79 mmol) in dichloromethane (2.5 mL) and triethylamine (0.28 mL, 1.97 mmol) were added and the mixture was allowed to warm to ambient temperature. After 2 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate (3×). 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 (213 mg). MS 540.2005 (M+1).

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