反应详情

温度

50 °C

A mixture of 1,2,2-trimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (131 mg, 0.50 mmol), 1 M aqueous HCl (2.5 mL, 2.5 mmol) and MeOH (2.5 mL) was stirred at 50° C. for 1 h. After addition of saturated aqueous NaHCO3, the organic materials were extracted with EtOAc. After removal of the solvent at reduced pressure, the residue was mixed with 4,4-difluorocyclohexanone (335 mg, 2.5 mmol), CSA (12 mg, 0.050 mmol), MgSO4 (96 mg, 1.0 mmol) and DMA (1 mL). After stirred at 80° C. for 1.5 h, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc/hexane to give the title compound (121 mg, 72%) as a yellow solid:

1. extractionthe organic materials were extracted with EtOAc
2. customAfter removal of the solvent at reduced pressure
3. stirringAfter stirred at 80° C. for 1.5 h
4. customto quench
5. customthe reaction
6. extractionThe organic materials were extracted with EtOAc
7. washThe combined extracts were washed with water and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. customAfter removal of the solvent at reduced pressure
11. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc)
12. customcrystallized from MeOH/EtOAc/hexane