反应详情

温度

70 °C

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine (50 mg, 0.18 mmol) from Example 5 step 3 and 2-fluoro-5-(1H-tetrazol-1-yl)pyridine (35.6 mg, 0.20 mmol) from step 1 were added in NMP (0.89 mL), then potassium carbonate (73.8 mg, 0.53 mmol) was added and the reaction was heated to 70° C. 6.5 hours. The reaction was cooled to room temperature, water (10 mL) was added, extracted with ethyl acetate (20 mL), second wash with brine (10 mL). The organic phase was 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 40% ethyl acetate/hexane to give the title compound as a white-solid.

1. custom6.5 hours
2. temperatureThe reaction was cooled to room temperature
3. extractionextracted with ethyl acetate (20 mL)
4. washsecond wash with brine (10 mL)
5. dry with materialThe organic phase was dried 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 40% ethyl acetate/hexane