反应详情

温度

90 °C

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine (50 mg, 0.18 mmol) from step 3, Example 5 and 2-chloro-5-(1H-1,2,4-triazol-1-yl)pyrazine (35.6 mg, 0.20 mmol) were added in NMP (0.89 mL), then potassium carbonate (73.8 mg, 0.53 mmol) was added and the reaction was heated to 90° C. overnight. The reaction was cooled to room temperature, water (10 mL) was added and drops of acetic acid were added to adjust pH value to ˜4, extracted with ethyl acetate (20 mL), second wash with brine (10 mL). The water phase was back extracted with ethyl acetate (10 mL×2). The organic phase were combined and dried by magnesium sulfate, filtered and concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 30% ethyl acetate/hexane to give the title compound as a white solid.

1. temperatureThe reaction was cooled to room temperature
2. extractionextracted with ethyl acetate (20 mL)
3. washsecond wash with brine (10 mL)
4. extractionThe water phase was back extracted with ethyl acetate (10 mL×2)
5. dry with materialdried by magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
9. washeluting with 30% ethyl acetate/hexane