反应详情

To a solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1H-pyrazol-4-yl)-pyrazin-2-ylamine (295 mg, 0.80 mmol) in anhydrous DMF (4 mL) was added NaH (60% in mineral oil, 30.7 mg, 0.80 mmol). The mixture was stirred at ambient temperature under nitrogen for 0.5 h, and then 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (223.5 mg, 0.80 mmol) was introduced. The reaction mixture was heated to 90° C. oil bath for 0.5 h under nitrogen, and cooled to ambient temperature. Water was added slowly to the mixture, which was extracted with EtOAc, washed with brine, and dried over Na2SO4. The crude product was purified on a silica gel column to provide 4-(4-{5-amino-6-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (265 mg, 59% yield).

1. temperatureThe reaction mixture was heated to 90° C. oil bath for 0.5 h under nitrogen
2. temperaturecooled to ambient temperature
3. extractionwas extracted with EtOAc
4. washwashed with brine
5. dry with materialdried over Na2SO4
6. customThe crude product was purified on a silica gel column