Phosphorus oxychloride → 4-Chloro-6,7-dimethoxyquinazoline

Participants

Reaction Steps

The key starting material, 4-chloro-6,7 -dimethoxyquinazoline, was prepared according to published procedures (Nomoto, et al., 1990, Chem. Pharm. Bull., 38:1591–1595; Thomas C. L., 1970, IN:Catalyc Processes and Proven Catalysts, Academic Press, New York, N.Y.) as outlined below in Scheme 1. Specifically, 4.5-dimethoxy-2-nitrobenzoic acid (compound 1) was treated with thionyl chloride to form acid chloride, followed by reacting with ammonia to yield 4,5-dimethoxy-2-nitrobenzamide (compound 2). Compound 2 was reduced with sodium borohydride in the presence of catalytic amounts of copper sulphate to give 4,5-dimethoxy-2-aminobenzamide (compound 3), which was directly refluxed with formic acid to yield 6,7-dimethoxyquinazoline-4(3H)-one (compound 4). Compound 4 was refluxed with phosphorus oxytrichloride to give 4-chloro-6,7-dimethoxyquinazoline (compound 5) in good yield.

Provenance & Evidence