Synthesis of [13C6]3,4-diaminobenzoic acid as a precursor for stable isotope labeled benzimidazoles

The synthesis of ¹³C₆]3,4-diaminobenzoic acid from commercially available ¹³C₆]aniline is described in six steps. Salient features of this route include the preparation of a differentially protected 3,4-diaminobenzonitrile, hydrogen gas free aromatic nitro group reduction with ammonium formate and facile benzimidazole ring closure of the ortho-arylenediamine with triethylorthoformate. This stable-labeled 3,4-diaminobenzoic acid is an ideal M+6]isotopomer to synthesize complex benzimidazole fragments for mass spectrometry internal assays.