Ethanethiol → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-ethylsulfanyl-6-methoxy-3-quinolinecarbonitrile

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Reaction Steps

To a mixture of sodium hydride (82 mg, 2.04 mmol) in 6 mL of tetrahydrofuran is added ethanethiol (77 mg, 1.12 mmol) in 6 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature for 2 hours. A solution of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) in 7 mL of tetrahydrofuran is added via syringe and the reaction mixture is heated at 70° C. for 5 hours, then cooled to room temperature. The reaction volume is reduced by concentration in vacuo and then partitioned between ethyl acetate and water. The aqueous layer is extracted with additional ethyl acetate and the organic layers are combined and washed with water. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 10% to 30% ethyl acetate in hexane to provide 154 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-ethylsulfanyl-6-methoxy-3-quinolinecarbonitrile, mp 212-214° C.

Provenance & Evidence