反应详情

温度

0 °C

To a solution of 2-(3,4-difluorophenyl)ethanol (221 mg, 1.400 mmol) in THF (5 mL) was added NaH (112 mg, 2.80 mmol) at 0° C. The reaction mixture was stirred for 10 min at 0° C., and then tert-butyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate (400 mg, 1.400 mmol) was added and stirred for another 0.5 hr at 0° C. The mixture was poured into ice water and extracted with DCM (10 mL×3). The combined extracts were washed with water (10 mL) then brine (10 mL) and then dried over Na2SO4. The mixture was concentrated to give tert-butyl 8-(3,4-difluorophenethoxy)-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate. A solution of the crude compound in 1,4-dioxane (10 mL) was added 4N HCl, stirred for 3 h at rt, and then concentrated. The residue was purified by MDAP to afford the HCl salt of the title product as a white solid (46 mg, 10.8% yield).

1. stirringstirred for another 0.5 hr at 0° C
2. extractionextracted with DCM (10 mL×3)
3. washThe combined extracts were washed with water (10 mL)
4. dry with materialbrine (10 mL) and then dried over Na2SO4
5. concentrationThe mixture was concentrated