反应详情

温度

100 °C

A mixture of 9-chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (Example 185, 2.10 g, 4.27 mmol) and phosphoryl chloride (11 mL) was stirred at 100° C. for 5 hr. The mixture was concentrated in vacuo, diluted with water, neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with diisopropyl ether/n-hexane to give the title compound as a colorless powder (889 mg, 1.79 mmol, 42%).

1. concentrationThe mixture was concentrated in vacuo
2. additiondiluted with water
3. extractionextracted with ethyl acetate
4. washThe combined organic layer was washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
9. concentrationThe filtrate was concentrated in vacuo
10. customto give the solid, which
11. washwas washed with diisopropyl ether/n-hexane