Sodium Chloride → 3-Bromo-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

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Reaction Steps

To a suspension of sodium hydride (438 mg of a 60% dispersion in mineral oil, 10.96 mmol) in 60 mL of tetrahydrofuran is added 2,4-dichloro-5-methoxyaniline (2.10 g, 10.96 mmol). The mixture is heated at reflux for 1 hour and then cooled to room temperature and 1.50 g of a 1 to 2.4 mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine-6-carbonitrile and 3,7-dibromothieno[3,2-b]pyridine-6-carbonitrile is added. The reaction mixture is heated at reflux for 2 hours then cooled to room temperature and treated with saturated aqueous sodium chloride. The organic layer is separated and the aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of ethyl acetate in hexane to provide 1.78 g of 3-bromo-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as a tan solid, mp 265–266° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.44 (s, 1H), 7.79 (s, 1H), 8.31 (s, 1H), 8.72 (s, 1H), 9.93 (s, 1H); MS 427.9, 429.9, 431.8 (M+H)+.

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