反应详情

温度

115 °C

Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (1.02 g, 4.8 mmol) and 2-amino-3-methyl-benzamide (0.6 g, 4.0 mmol) were combined with trimethylsilyl polyphosphate (8.0 mL) and the mixture was heated at 115° C. for 18 h with vigorous stirring. The mixture was allowed to cool to rt, then the mixture was partitioned between water (15 mL) and ethyl acetate (15 mL). The organic layer was separated and the aqueous layer (pH˜1) was extracted with ethyl acetate (30 mL×3). The combined organic layers were separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:10 to 1:1 EtOAc/hexanes to afford 2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-methyl-3H-quinazolin-4-one as an off-white solid (0.6 g, 29%).

1. temperatureto cool to rt
2. customthe mixture was partitioned between water (15 mL) and ethyl acetate (15 mL)
3. customThe organic layer was separated
4. extractionthe aqueous layer (pH˜1) was extracted with ethyl acetate (30 mL×3)
5. customThe combined organic layers were separated
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography
10. washeluting with 1:10 to 1:1 EtOAc/hexanes