2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → Methyl 4-(5-cyano-4-oxo-4,7-dihydrothieno[2,3-b]pyridin-2-yl)butanoate

Participants

Reaction Steps

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.

Provenance & Evidence