反应详情

温度

80 °C

tert-butyl(25)-2-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)piperidine-1-carboxylate (1.41 g) produced in Example 83, step B, [3-(trifluoromethyl)-1-trityl-1H-pyrazol-4-yl]boronic acid (1.72 g), sodium carbonate (902 mg), ethanol (15 mL) and water (3 mL) were placed in a flask, and the atmosphere in the flask was purged with argon. Tetrakis(triphenylphosphine)palladium(0) (197 mg) was added, the atmosphere in the flask was purged again with argon, and the mixture was stirred at 80° C. for 15 hr. Ethyl acetate (20 mL) and water (10 mL) were added to the reaction mixture, and the separated aqueous layer was extracted with ethyl acetate (10 mL×2). The combined organic layers were washed with brine (20 mL) and dried over anhydrous magnesium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/hexane), and the object fraction was concentrated under reduced pressure to give tert-butyl(2S)-2-{4-oxo-6-[3-(trifluoromethyl)-1-trityl-1H-pyrazol-4-yl]-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl}piperidine-1-carboxylate as a colorless oil. To a solution of tert-butyl(2S)-2-{4-oxo-6-[3-(trifluoromethyl)-1-trityl-1H-pyrazol-4-yl]-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl}piperidine-1-carboxylate produced above in methanol (4 mL) was added 4M hydrochloric acid/ethyl acetate solution (1 mL), and the mixture was stirred at 60° C. for 15 hr. The precipitated solid was collected by filtration to give the title compound (530 mg) as a colorless solid.

1. customthe atmosphere in the flask was purged with argon
2. additionTetrakis(triphenylphosphine)palladium(0) (197 mg) was added
3. customthe atmosphere in the flask was purged again with argon
4. additionEthyl acetate (20 mL) and water (10 mL) were added to the reaction mixture
5. extractionthe separated aqueous layer was extracted with ethyl acetate (10 mL×2)
6. washThe combined organic layers were washed with brine (20 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationInsoluble material was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane)
11. concentrationthe object fraction was concentrated under reduced pressure