反应详情

温度

80 °C

To a mechanically stirred suspension of 2-(2-methoxyphenyl)-7-methyl-3H-quinazolin-4-one (100 g, 0.37 mol) in 1 L toluene was added diisopropyl ethylamine (100 mL), followed by phosphorus oxychloride (69 g, 0.45 mol). The reaction was then heated to 80° C. for 4 h. The reaction mixture was distilled under reduced pressure to remove toluene, and the resulting residue was dissolved in 2.2 L CH2Cl2. Ice water was added, and the pH was adjusted to 8-9 with saturated aqueous sodium bicarbonate solution while maintaining the temperature below 20° C. The resulting organic layer was separated and the aqueous solution extracted with CH2Cl2, then the combined the organic layers were dried over sodium sulfate and distilled under reduced pressure. The crude product was dissolved 2:1 CH2Cl2/hexane, and the solution was passed through silica gel (2.5 kg, 60-120 mesh), followed by washing the silica bed with 2:1 CH2Cl2/hexane until the product eluted. The pure fractions were collected and combined, and the solvent was removed under reduced pressure. Hexane (500 mL) was added, and the mixture was stirred and filtered to give 4-chloro-2-(2-methoxy-phenyl)-7-methyl-quinazoline as a white to off-white solid (77 g, 72%). mp 161-164° C. 1H NMR (CDCl3) δ 2.6 (s, 3H), 3.9 (s, 3H), 6.9-7.2 (m, 2H), 7.4-7.6 (m, 2H), 7.7-8 (d, 2H), 8.2 (d, 1H) ppm; 13C NMR (CDCl3) δ 22.23, 56.06, 112.2, 120.26, 120.69, 125.34, 127.94, 130.45, 131.08, 131.08. M/z (obs., [m+H]+)=285.

1. distillationThe reaction mixture was distilled under reduced pressure
2. customto remove toluene
3. dissolutionthe resulting residue was dissolved in 2.2 L CH2Cl2
4. additionIce water was added
5. temperaturewhile maintaining the temperature below 20° C
6. customThe resulting organic layer was separated
7. extractionthe aqueous solution extracted with CH2Cl2
8. dry with materialwere dried over sodium sulfate
9. distillationdistilled under reduced pressure
10. dissolutionThe crude product was dissolved 2:1 CH2Cl2/hexane
11. washby washing the silica bed with 2:1 CH2Cl2/hexane until the product
12. washeluted
13. customThe pure fractions were collected
14. customthe solvent was removed under reduced pressure
15. additionHexane (500 mL) was added
16. filtrationfiltered