反应详情

温度

100 °C

Tert-butyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (0.60 g, 1.3 mmol) was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (5 mL). When LC/MS analysis revealed the deprotection of the Boc group, the mixture was concentrated to dryness under reduced pressure. Diethyl ether was evaporated three times from the crude material in order to afford a solid residue. The trifluoroacetate salt was dissolved in approximately 15 mL of warm acetone and added to a 10-20 mL Smith process vial charged with 2,2,2-trifluoroethyl trichloromethanesulfonate (0.56 g, 2.0 mmol). Potassium carbonate (0.90 g, 6.5 mmol) was added and the suspension was heated in the microwave for one hour at 100° C. After cooling to room temperature, the mixture was concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. 3-(6-Chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane was thus obtained as a yellow foam (0.55 g, 100%). MS (ES+): 430.9, 432.9 (M+H)+

1. concentrationthe mixture was concentrated to dryness under reduced pressure
2. customDiethyl ether was evaporated three times from the crude material in order
3. customto afford a solid residue
4. additionadded to a 10-20 mL Smith process
5. temperatureAfter cooling to room temperature
6. concentrationthe mixture was concentrated to dryness under reduced pressure
7. customThe residue was partitioned between ethyl acetate and water
8. extractionThe aqueous phase was extracted three times with ethyl acetate
9. washThe combined extracts were washed with saturated aqueous sodium chloride solution
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated to dryness under reduced pressure