Methanol → Thieno[3,2-b]-pyridine-6-carbonitrile 14

Participants

Reaction Steps

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (200 mg, 0.42 mmol), 1-methyl-4-prop-2-ynyl-piperazine (87.0 mg, 0.65 mmol), 9.7 mg of tetrakis(triphenylphosphine)palladium(0) and 2.0 mg of copper(I) iodide in 2 mL of triethylamine and 7 mL of benzene is heated at reflux for 5 hours. The mixture is cooled to room temperature and 2 mL of methanol are added. The solvents are removed in vacuo and the residue is purified by preparative thin layer chromatography developing with 12% methanol in dichloromethane to give a solid which is triturated with ether containing several drops of dichloromethane, to provide 89.6 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[3-(4-methylpiperazin-1-yl)prop-1-ynyl]thieno[3,2-b]pyridine-6-carbonitrile as a yellow solid, mp 172–173° C.; 1H NMR (DMSO-d6) δ 2.18 (s, 3H), 2.37 (s, 4H), 2.49 (s, 4H), 3.59 (s, 2H), 3.85 (s, 3H), 7.37 (s, 1H), 7.62 (s, 1H), 7.78 (s, 1H), 8.62 (s, 1H), 9.82 (s 1H); MS 486.1, 488.1 (M+H)+.

Provenance & Evidence