Study On Synthesis Of Marbofloxacin

Marbofloxacin,a new generation of fluoroquinolone agent,is a dedicated antibacterial drug for mammals approved by the U.S.FDA.Now marbofloxacin is primarly used for the treatment of infectious diseases in veterinary clinical.With broad antibacterial spectrum and strong antibacterial activity,marbofloxacin has good efficacy in treating Gram-negative bacteria,Gram-positive bacteria,anaerobic bacteria and even mycoplasma.Therefore,it has extensive prospect as an antibacterial drug.In this experiment,tetrafluoro benzoic acid was used as raw material for synthesis of marbofloxacin.Undergoing chloroformylation,Michael addition and nucleophilic substitution,intermediate 3-(benzylmethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester was obtained.And after amine exchange and primary cyclization,an intermediate of 6,7,8-trifluoro-1,4-dihydro-1-(N-methylformamido)-4-oxo-3-quinolinecar-boxylate was obtained.The obtained compound condensed with N-methyl piperazine to prepare the ethyl ester of 6,8-difluoro-1,4-dihydro-1-(N-methylformamido)-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid and the final product marbofloxacin was synthesized through hydrolysis and secondary cyclization.The research on the detailed reacting conditions was undertaken and the optimal condition was given.The results of this research laid a solid foundation for marbofloxacin industrial production.Marbofloxacin and the primary intermediates were characterized by FT-IR,DSC and 1H-NMR,the quality of marbofloxacin product was detected according to European Pharmacopeia(EP)and the results showed the specifications can pass all the requirements.