Phosphorus oxychloride → 7-Chlorothieno[3,2-b]pyridine-6-carbonitrile

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Reaction Steps

A mixture of 7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carbonitrile (3.00 g, 17.0 mmol) and 25 mL of phosphorous oxychloride is heated at reflux for 10 minutes. The reaction mixture is cooled to room temperature and the dark solids are removed by filtration. The filtrate is poured into hexane and allowed to stand at room temperature. The solvent is decanted off and the residual oil is dissolved in ethyl acetate and the solution is washed with water. The organic layer is dried over magnesium sulfate, filtered and passed through silica gel. The filtrate is concentrated in vacuo to give 770 mg of the desired product as a dark orange solid. A portion of this material is purified by flash column chromatography eluting with 1:1 ethyl acetate:hexane to provide 7-chlorothieno[3,2-b]pyridine-6-carbonitrile as tan crystals, mp 110–111° C.; 1H NMR (DMSO-d6) δ 7.81 (d, J=5 Hz, 1H), 8.59 (d, J=5 Hz, 1H), 9.12 (s, 1H); MS 194.9 (M+H)+.

Provenance & Evidence