反应详情

A suspension of 4-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (6.28 9, 14.8 mmol) in 54 mL of acetonitrile and 2.0 mL of methanol was heated to reflux and phosphorous oxychloride (8.3 mL, 88.8 mmol) was added dropwise. The mixture was heated at reflux for 17 hours. The resultant solution was concentrated in vacuo and acetonitrile was added to the residue. The solid was collected by filtration, washed with acetonitrile. The solid was suspended in tetrahydrofuran and neutralized with concentrated ammonium hydroxide. After stirring for 30 minutes, water was added and the mixture was stirred for 1 hour. The solid was collected by filtration, washed with water, followed by 1:1 diethyl ether and hexane. The light yellow solid was dried in vacuo to provide 2.2 g (37%) of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-fluoro-3-quinolinecarbonitrile, mp 185-187° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.95 (t, J=7 Hz, 3H), 3.87 (s, 3H), 4.29 (q, J=7 Hz, 2H), 7.39 (s, 1H), 7.66-7.81 (m, 2H), 8.09 (d, J=9 Hz, 1H), 8.49 (s, 1H), 9.80 (s, 1H); MS (ES) m/z 406.1, 408.2 (M+H)+

1. temperaturewas heated
2. temperatureto reflux
3. temperatureThe mixture was heated
4. temperatureat reflux for 17 hours
5. concentrationThe resultant solution was concentrated in vacuo and acetonitrile
6. additionwas added to the residue
7. filtrationThe solid was collected by filtration
8. washwashed with acetonitrile
9. additionwater was added
10. stirringthe mixture was stirred for 1 hour
11. filtrationThe solid was collected by filtration
12. washwashed with water
13. customThe light yellow solid was dried in vacuo