反应详情

温度

50 °C

Triethylamine (55 μL, 0.39 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,6-difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (40 mg, 0.10 mmol) and 4-nitrophenyl chloroformate (22 mg, 0.11 mmol) in tetrahydrofuran (5 mL) at 0° C. After 30 min, 6-methyl-4-piperidin-4-ylpyridazin-3(2H)-one (38 mg, 0.20 mmol), triethylamine (55 μL, 0.39 mmol) and chloroform (5 mL) were added and the mixture was heated to 50° C. After 30 min, the reaction mixture was allowed to cool to ambient temperature. Saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane. The organic extracts were 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 (15 mg). MS 591.2536 (M+1).

1. waitAfter 30 min
2. temperatureto cool to ambient temperature
3. extractionthe mixture was extracted with dichloromethane
4. washThe organic extracts were 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)