反应详情

温度

60 °C

Triethylamine (50 μL, 0.358 mmol) was added to a solution of the bis hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-9-amine (60 mg, 0.143 mmol) and 1,1′-carbonyldiimidazole (41 mg, 0.25 mmol) in tetrahydrofuran (3 mL) at 0° C. After 25 min, 3-piperidin-4-ylquinolin-2(1H)-one (33 mg, 0.143 mmol) and dichloromethane (3 mL) were added and the mixture heated to 60° C. After 16 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with dichloromethane (3×). The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane→95% dichloromethane/(10% ammonium hydroxide/methanol)]. Repurification by reverse phase HPLC (C-18, 10% acetonitrile/water→100% acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (57.5 mg). MS 601.2312 (M+1).

1. waitAfter 16 h
2. extractionthe mixture was extracted with dichloromethane (3×)
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/(10% ammonium hydroxide/methanol)]
8. customRepurification by reverse phase HPLC (C-18, 10% acetonitrile/water→100% acetonitrile with 0.1% trifluoroacetic acid)