Methyl iodide → 7-Chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile

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Reaction Steps

To a solution of 7-chlorothieno[3,2-b]pyridine-6-carbonitrile (500 mg, 2.57 mmol) in 15 mL of tetrahydrofuran at −78° C. is added dropwise 2.0 M lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (1.6 mL, 3.21 mmol). After stirring for 40 minutes, iodomethane (616 mg, 0.27 mL, 4.34 mmol) is added dropwise over 7 minutes. The reaction mixture is stirred at −78° C. for 5 hours, then the mixture is partitioned between 20 mL of dichloromethane and 10 mL of water. The organic layer is washed with a saturated aqueous ammonium chloride solution, followed by saturated aqueous sodium chloride, then dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 5% ethyl acetate in hexane to 20% ethyl acetate in hexane to provide 274 mg of 7-chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile as a white solid, mp 163–164° C.; 1H NMR (DMSO-d6) δ 2.73 (s, 3H), 7.55 (s, 1H), 9.03 (s, 1H); MS 209.0, 211.1 (M+H)+.

Provenance & Evidence