Improvement in synthesis of 3'-N-demethylazithromycin and its derivatives

3'-N-demethylazithromycin is an impurity in azithromycin drug. It is derived by demethylation of azithromycin, i.e., azithromycin loses a methyl group on the 3'-N position. In this study, bulk product was purified with chromatographic separation. It was observed that 3'-N-demethylazithromycin was also a precursor of other impurities. Simultaneously, another derivative was synthesized, i.e., 3'-N-demethyl-3'-N-formylazithromycin. Reaction conditions were optimized with the HPLC method and good-quality and high-yield derivative product was achieved. The structures of derivatives were identified by ¹H-NMR and MS.