Synthesis and Characterization of Impurities of a Common and Advanced Intermediate of Candesartan and Azilsartan Antihypertensive Drugs

Six impurities were identified in the lab development batches during the course of benzimidazole intermediate (1) synthesis by reverse phase HPLC method. Intermediate 1 is used as a common and advanced intermediate in the synthesis of candesartan and azilsartan. All the impurities were characterized by IR, NMR, LC/MS and CHN analyses, which included an isomer of intermediate 11 (impurity 19), desethyl analogue of 1 (impurity 20), desethoxy analogue of 1 (impurity 21), methyl analogue of 1 (impurity 22), cyanobiphenyl benzimidazole (impurity 25) and cyanobiphenyl derivative of 1 (impurity 26). The synthesis and characterization of these impurities are presented.