反应详情

To a slurry of 3-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidin-1-yl]-3-oxo-propanenitrile (74.mg, 0.16 mmol) in ethanol (3 mL) was added 3-methy)oxetane-3-carbaldehyde (78.54 mg, 0.78 mmol) and then piperidine (0.02 mL, 0.16 mmol) and the mixture heated to 80° C. with stirring. After 3 h, the mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, and the filtered. Solvents were removed to afford an oil which was purified by column chromatography (gradient from neat methylene chloride to 95-5 methylene chloride:MeOH). The pure fractions were concentrated, then taken up in acetonitrile/water, frozen and lyophilized to afford 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(3-methyloxetan-3-yl)prop-2-enenitrile as a colorless solid weighing 14 mg.

1. temperaturethe mixture was cooled
2. custompartitioned between ethyl acetate and water
3. washThe organic phase was washed with brine
4. dry with materialdried over sodium sulfate
5. customSolvents were removed
6. customto afford an oil which
7. customwas purified by column chromatography (gradient from neat methylene chloride to 95-5 methylene chloride:MeOH)
8. concentrationThe pure fractions were concentrated
9. temperaturefrozen