3,4-Dimethoxy-6-nitrobenzamide → 2-Amino-4,5-dimethoxybenzamide

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Reaction Steps

4,5-Dimethoxy-2-nitrobenzoic acid (1) was treated with thionyl chloride and then reacted with ammonia to give 4,5-dimethoxy-2-nitrobenzamide (2) as described by F. Nomoto et al. Chem. Pharm. Bull. 1990, 38, 1591-1595. The nitro group in compound (2) was reduced with sodium borohydride in the presence of copper sulfate (see C. L. Thomas Catalytic Processes and Proven Catalysts Academic Press, New York (1970)) to give 4,5-dimethoxy-2-aminobenzamide (3) which was cyclized by refluxing with formic acid to give 6,7-dimethoxyquinazoline-4(3H)-one (4). Compound (4) was refluxed with phosphorus oxytrichloride to provide compound (5), which is a useful intermediate for preparing compounds of formula I wherein X is NH. Reaction of compound (5) with the requiste aniline provided the following compounds of formula I:

Provenance & Evidence