反应详情

A mixture of 4-(5-amino-thiophen-2-yl)-butyric acid methyl ester (1.00 g, 5.0 mmol) and ethyl (ethoxymethylene)cyanoacetate (930 mg, 5.5 mmol) in 50 mL of toluene is heated at reflux for 1 hour. The reaction mixture is concentrated and 50 mL of Dowtherm-A is added. The mixture is heated at reflux for 3 hours and cooled to room temperature. The crude reaction mixture is passed through a short pad of silica gel, eluting with dichloromethane followed by 10% methanol in dichloromethane. The crude product is further purified by flash column chromatography eluting with 10% methanol in dichloromethane followed by another flash column chromatography eluting with 10% methanol in ethyl acetate to provide 136 mg of methyl 4-(5-cyano-4-oxo-4,7-dihydrothieno[2,3-b]pyridin-2-yl)butanoate as a tan solid.

1. temperatureis heated
2. temperatureat reflux for 1 hour
3. concentrationThe reaction mixture is concentrated
4. addition50 mL of Dowtherm-A is added
5. temperatureThe mixture is heated
6. temperatureat reflux for 3 hours
7. customThe crude reaction mixture
8. washeluting with dichloromethane
9. customThe crude product is further purified by flash column chromatography
10. washeluting with 10% methanol in dichloromethane
11. washeluting with 10% methanol in ethyl acetate