4-CHLOROTHIENO[2,3-B]PYRIDINE-5-CARBONITRILE

63873-60-9

63873-61-0

The general procedure for the synthesis of 4-chlorothieno[2,3-b]pyridine-5-carbonitrile as starting material via chlorination was as follows: first, bis-(2-thienylammonium) hexachlorostannate (2) was produced by the reduction of 2-nitrothiophene (1) by the reaction of tin and hydrochloric acid. Subsequently, the compound was subjected to a condensation reaction with ethyl (ethoxymethylene) cyanoacetate in pyridine at 40-50 °C over 24 h to give ethyl α-cyano-β-(N-2-thienylammonium) acrylate (3) in 88% yield. Next, 4-hydroxythieno[2,3-b]pyridine-5-carbonitrile (4) was isolated in 78% yield by refluxing the acrylate through Dowtherm at 250 °C for 40 min, which induced cyclization of the acrylate, followed by precipitation from petroleum ether. Finally, compound 4 was refluxed with phosphoryl chloride at 110 °C for 6 h for chlorination reaction to afford the target product 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (5) in 76% yield.