反应详情

A suspension of 3-bromo-4-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (4.00 g, 8.50 mmol) in 200 mL of acetonitrile was heated to reflux and phosphorous oxychloride (5.0 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 1 hour and then extracted with a large volume of ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and filtered. The filtrate was reduced in volume until solids appeared. The solids were collected by filtration, washed with diethyl ether and hexanes to provide 1.73 g of 7-bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile as a light tan solid, mp >250° C. 1H NMR (400 MHz, DMSO-d6) δ 3.87 (s, 3H), 4.04 (s, 3H), 7.41 (s, 1H), 7.78 (s, 1H), 7.99(s, 1H), 8.22 (s, 1H), 8.48 (s, 1H), 9.93 (s, 1H); MS (ES) m/z449.9, 451.9, 453.9 (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. extractionextracted with a large volume of ethyl acetate
9. washThe organic layer was washed with saturated aqueous sodium bicarbonate
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. filtrationThe solids were collected by filtration
13. washwashed with diethyl ether and hexanes