反应详情

A mixture of 3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl trifluoromethanesulfonate (835 mg, 1.60 mmol), 2-formyl-4-furan boronic acid (446 mg, 3.21 mmol), and tetrakis(triphenylphosphine)pallidium (0) (20 mg) in 40 mL of ethylene glycol dimethyl ether and 25 mL of saturated aqueous sodium bicarbonate is heated at reflux for 3 hours and then cooled to room temperature. The reaction mixture is partitioned between dichloromethane and water. The aqueous layer is extracted with 10% methanol in ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. Diethyl ether is added to the residue and the solid is collected by filtration to provide 723 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-(5-formyl-3-furyl)-6-methoxy-3-quinolinecarbonitrile as a light yellow solid, mp 238-241° C.; 1H NMR (DMSO-d6) δ 3.88 (s, 3H), 4.09 (s, 3H), 7.38 (s, 1H), 7.76 (s, 1H), 8.01 (s, 1H), 8.29 (broad s, 2H), 8.48 (s, 1H), 8.77 (s, 1H), 9.71 (s, 1H), 9.87 (s, 1H); MS 468.0, 470.0 (M+H)+; HRMS calcd: 468.05124, found: 468.0511 (M+H)+.

1. temperatureis heated
2. temperatureat reflux for 3 hours
3. customThe reaction mixture is partitioned between dichloromethane and water
4. extractionThe aqueous layer is extracted with 10% methanol in ethyl acetate
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. additionDiethyl ether is added to the residue
9. filtrationthe solid is collected by filtration