反应详情

温度

120 °C

A mixture of 6-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.125 g, 0.480 mmol), 4-pyrazoleboronic acid pinacol ester (0.279 g, 1.44 mmol), sodium carbonate (0.254 g, 2.40 mmol), 1,2-dimethoxyethane (2.4 mL) and water (1.2 mL) was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.041 g, 0.050 mmol) was added to the mixture and the mixture was purged with argon again. The mixture was stirred at 120° C. for 4 h in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (50 mL). Extraction with ethyl acetate/THF (3:1, 2×50 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure were carried out. The residue was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol). The fractions containing the desired product were collected. Some amount of starting material was recovered, reacted and purified with the above conditions again. The fractions containing the desired product were combined and concentrated in vacuo. This residue was further purified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol), then triturated with dichloromethane. The precipitate was collected by filtration to afford the title compound (0.0308 g, 26%) as a yellow solid:

1. customwas purged with argon
2. customthe mixture was purged with argon again
3. additionThe mixture was poured into sat. aqueous sodium hydrogen carbonate (50 mL)
4. extractionExtraction with ethyl acetate/THF (3:1, 2×50 mL)
5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
6. customThe residue was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol)
7. additionThe fractions containing the desired product
8. customwere collected
9. customSome amount of starting material was recovered
10. customreacted
11. custompurified with the above conditions again
12. additionThe fractions containing the desired product
13. concentrationconcentrated in vacuo
14. customThis residue was further purified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol)
15. customtriturated with dichloromethane
16. filtrationThe precipitate was collected by filtration