Hydrochloric Acid → 3-Cyano-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]-4-[4-(3-methoxyprop-1-ynyl)-2,3-methylenedioxyanilino]quinoline dihydrochloride salt

Participants

Reaction Steps

A mixture of 4-chloro-3-cyano-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinoline (165 mg) and 4-(3-methoxyprop-1-ynyl)-2,3-methylendioxyaniline (123 mg) in 1-propanol (10 ml) was treated with a 1.0M solution of hydrogen chloride in diethyl ether (0.5 ml) then stirred and heated at reflux for 2 hours. On cooling a solid precipitated from the reaction mixture. The resulting suspension was basified with aqueous ammonia and evaporated to a gum. This residue was purified by multi-injection preparative RP HPLC [Kromasil C18 5 μm silica column, 100 mm×10 mm; eluted with a mixture of acetonitrile (55%) and 0.1% aqeous ammonia solution (45%)]. After isolation, the major product was converted to its dihydrochloride salt in acetonitrile using two equivalents of a 1.0M solution of hydrogen chloride in diethyl ether. The title compound was thus obtained as a yellow solid (81 mg); NMR Spectrum: (DMSOd6 & CD3COOD, 373K) 2.17 (m, 2H), 2.38 (m, 2H), 2.77 (s, 3H), 3.30 (m, 4H), 3.37 (s, 3H), 3.96 (s, 3H), 4.33 (s, 2H), 5.04 (m, 1H), 6.12 (s, 2H), 6.92 (d, 1H), 6.97 (m, 2H), 7.08 (s, 1H), 8.63 (s, 1H); Mass Spectrum: M+H+ 501.

Provenance & Evidence