Preparation and Characterization of Impurities of Teriflunomide—An Immunomodulatory Agent

Teriflunomide is an immunomodulatory agent used in the treatment of rheumatoid arthritis. Our present research work depicts the origin, preparation and characterization of impurities of teriflunomide: (2Z)-4-chloro-2-cyano-N-[4-(trifluoromethyl]phenyl]-3-hydroxy-2-butenamide (chloromethyl teriflunomide), (2Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-pentenamide (ethyl teriflunomide), two positional isomers namely (2Z)-2-cyano-3-hydroxy-N-[2-(trifluoromethyl)phenyl]-2-butenamide (2-isomer of teriflunomide) and (2Z)-2-cyano-3-hydroxy-N-[3-(trifluoromethyl)phenyl]-2-butenamide (3-isomer of teriflunomide). These impurities are process related impurities which are useful to finalize the specifications of teriflunomide drug substance. These synthesized impurities were characterized by ¹³C, ¹H NMR, HRMS and HPLC analysis.