反应详情

A suspension of 3-(3-chloropropoxy)-4-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (462 mg, 0.95 mmol) in 40 mL of acetonitrile was heated to reflux and phosphorous oxychloride (0.60 mL) was added dropwise, via syringe. The reaction mixture was heated at reflux overnight, then cooled to room temperature and concentrated in vacuo. The residue was cooled to 0° C. and saturated aqueous sodium bicarbonate was added. The mixture was stirred for 10 minutes and the solid was collected by filtration, washed with water. The solid was suspended in hot ethyl acetate and methanol and then filtered to provide 200 mg of 7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 2.30 (m, 2H), 3.84 (t, J=6 Hz, 1H), 3.88 (s, 3H), 4.01 (s, 3H), 4.32 (t, J=6 Hz, 2H), 7.46 (s, 1H), 7.51 (s, 1H), 7.81 (s, 1H), 8.14 (s, 1H), 8.81 (s, 1H), 10.83 (br s, 1H), MS (ES) m/z 466.1, 468.1 (M+H)+.

1. temperaturewas heated
2. temperatureto reflux
3. temperatureThe reaction mixture was heated
4. temperatureat reflux overnight
5. concentrationconcentrated in vacuo
6. temperatureThe residue was cooled to 0° C.
7. additionsaturated aqueous sodium bicarbonate was added
8. filtrationthe solid was collected by filtration
9. washwashed with water
10. filtrationmethanol and then filtered