Hydrochloric Acid → 3-Butyn-2-ol, 4-(3-aminophenyl)-2-methyl-

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Reaction Steps

According to European Patent No. 1044969, erlotinib hydrochloride is prepared, either by (i) reacting 6,7-bis(2-methoxyethoxy)-N43-[(trimethylsilyl)ethynyl]phenyl-4-quinazolinamine monohydrochloride, obtained by the reaction of 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline with a solution of 3-[(trimethylsilyl)ethynyl]aniline in 2-propanol at reflux, with tetra-n-butylammonium fluoride in an aprotic solvent such as tetrahydrofuran, diethyl ether, dimethoxyethane, toluene, dichloromethane and chloroform, and then treating the reaction mass with concentrated hydrochloric acid in 2-propanol; or (ii) reacting 4-[3-[[6,7-bis(2-methoxyethoxy)-4-quinazolinyl]amino]phenyl]-2-methyl-3-butyn-2-ol or its monohydrochloride salt, obtained by the reaction of 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline with 4-(3-aminophenyl)-2-methyl-3-butyn-2-ol in acetonitrile at reflux, with an alkali-metal or alkaline-metal hydroxide such as sodium hydroxide, lithium hydroxide, cesium hydroxide, calcium hydroxide, magnesium hydroxide and potassium hydroxide, in an alcoholic solvent such as 1-butanol, 2-butanol and 2-propanol, and then treating the reaction mass with concentrated hydrochloric acid in an alcoholic solvent.

Provenance & Evidence