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

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Reaction Steps

The common synthetic intermediate 4-chloro-6,7-dimethoxyquinazoline 5 used for synthesizing all the tested compounds by following literature procedures (Scheme 1). 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 (Nomoto et al., 1990, Chem. Pharm. Bull 38: 1591-1595). The nitro group in compound 2 was reduced with sodium borohydride in the presence of copper sulfate (31) 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. The quinazolinone 4 was refluxed with phosphorus oxytrichloride to provide the key starting material 5 with good yield.

Provenance & Evidence