反应详情

温度

120 °C

A mixture of sodium (50 mg, 2.2 mmol) in 1 mL of 2-[2-(1-piperazinyl)ethoxy]ethanol is heated at 120° C. for 2 hours. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (150 mg, 0.38 mmol) is added and the reaction mixture is heated at 140-145° C. for 2 hours, then cooled to room temperature. The reaction mixture is partitioned between saturated sodium bicarbonate and ethyl acetate. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 3% methanol in dichloromethane to 1% ammonium hydroxide and 30% methanol in dichloromethane followed by recrystallization from acetone and hexane to provide 124 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{2-[2-(1-piperazinyl)-ethoxy]ethoxy)-3-quinolinecarbonitrile, mp 88-90° C.

1. temperaturethe reaction mixture is heated at 140-145° C. for 2 hours
2. temperaturecooled to room temperature
3. customThe reaction mixture is partitioned between saturated sodium bicarbonate and ethyl acetate
4. dry with materialThe organic layer is dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue is purified by flash column chromatography
8. washeluting with a gradient of 3% methanol in dichloromethane to 1% ammonium hydroxide and 30% methanol in dichloromethane
9. customfollowed by recrystallization from acetone and hexane