反应详情

温度

95 °C

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol from Example 2 Step D (1.82 g, 6.25 mmol) was added phosphorousoxychloride (20 mL) and the mixture was heated at 95° C. for 3 h. The mixture was concentrated under reduced pressure and then toluene (20 mL) was added and evaporated. The residue was dissolved in EtOAc and washed with saturated NaHCO3 (1×) and brine (1×), dried over Na2SO4, and concentrated. The residue was purified by silica gel chromatography eluting with 10-80% EtOAc/hexanes to afford 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline (1.59 g, 82%). 1H NMR (300 MHz, DMSO-d6) δ 8.61 (d, J=2.6 Hz, 1H), 8.38 (d, J=8.3 Hz, 1H), 8.17-8.29 (m, 2H), 8.06-8.15 (m, 1H), 7.96-8.06 (m, 2H); LC-MS (ESI) m/z 310 (M+H)+.

1. concentrationThe mixture was concentrated under reduced pressure
2. additiontoluene (20 mL) was added
3. customevaporated
4. dissolutionThe residue was dissolved in EtOAc
5. washwashed with saturated NaHCO3 (1×) and brine (1×)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe residue was purified by silica gel chromatography
9. washeluting with 10-80% EtOAc/hexanes