Methyl iodide → 4-Chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile

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Reaction Steps

To a solution of 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (0.3 g, 1.54 mmol) in 15 mL of tetrahydrofuran at −78° C. is added dropwise 2.0 M lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (0.93 mL, 1.85 mmol). After stirring for 45 min, a solution of iodomethane (0.115 mL, 1.85 mmol) in 1 mL of tetrahydrofuran is added dropwise. The reaction mixture is stirred at −78° C. for 4 hours, then dichloromethane and water are added. The mixture is allowed to warm to room temperature, then partitioned between water and dichloromethane. The organic layer is washed with a solution of sodium thiosulfate, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 1:9 ethyl acetate:hexane to provide 0.1 g of 4-chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile as colorless crystals, mp 101–102° C.; 1H NMR (DMSO-d6) δ 2.68 (s, 3H), 7.39 (s, 1H), 8.92 (s, 1H); MS 209.0 (M+H)+.

Provenance & Evidence