反应详情

Triethylamine (37 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 (1 mL) at 0° C. After 15 min, a solution of 4-piperidin-4-ylpyridazin-3(2H)-one (30 mg, 0.167 mmol) in dichloromethane (1 mL) and triethylamine (49 μL, 0.67 mmol) were added and the mixture allowed to warm to ambient temperature. After 4 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 (51 mg). MS 551.2152 (M+1).

1. waitAfter 4 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)