反应详情

温度

120 °C

To a mixture of sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (2.05 g, 9.62 mmol) and 2-amino-4-bromobenzamide (1.89 g, 8.75 mmol) was added trimethylsilyl polyphosphate (˜15 mL) and the mixture was stirred overnight at 120° C. Equal volumes of EtOAc and water were added and the resulting solution was stirred for 1 h. The EtOAc layer was washed with brine, dried over Na2SO4 and then concentrated under reduced pressure. Et2O was added and evaporated. Trituration of the residue with hexanes, followed by collection of the solid by filtration afforded 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol (2.49 g, 77%). 1H NMR (300 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.76 (s, 1H), 7.97-8.07 (m, 2H), 7.88 (d, J=8.3 Hz, 1H), 7.69-7.81 (m, 2H);

1. stirringthe resulting solution was stirred for 1 h
2. washThe EtOAc layer was washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated under reduced pressure
5. additionEt2O was added
6. customevaporated
7. filtrationTrituration of the residue with hexanes, followed by collection of the solid by filtration