N-Ethylpiperidine → 4-Amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline

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Reaction Steps

A mixture consisting of the product of (B), viz., 5,6-dimethoxyisoindoline hydrochloride (1.94 g.), together with 4-amino-2-chloro-6,7-dimethoxyquinazoline (2.16 g.) and N-ethylpiperidine (3.11 g.) all dissolved in 2-ethoxyethanol (60 ml.) was refluxed for a period of six hours, followed by cooling to room temperature (~25° C.). The resulting precipitate of 4-amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline hydrochloride (3.50 g., m.p. 318° C.) was then shaken with a mixture consisting of dichloromethane (1000 ml.) and 0.5N sodium hydroxide solution in 50% aqueous ethanol (200 ml.). On separation and ultimate evaporation of the organic layer there was obtained a solid material (2.4 g.), which was subsequently crystallized from ethanol to give pure final product as the free base compound (yield, 1.40 g.), m.p. 264°-6° C.

Provenance & Evidence