Study On The Synthesis And Improvement Of The Intermedia Of Gemifloxacin

The work of tins research is devoted to the synthesis of gemifloxacin, chemical name: 7-(4-aminomethyl-3-methyloxyiminopynolidim-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid, it's jointed by the naphthyridine nucler and the branched-chain.Naphthyridine nucler's chemical name : 7-chlor-l-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.Because of the difference between Gemifloxacin's nucler and others before,using N instead of C in direction-1, this work improved the yield and purity of the product with reactive mechanism, The appropriate reaction conditions of chlorobenzene reaction : the proportion of socl₂ and 2,6-dichloro-5-fluoro-nicotine acid is 1.8:1.N N-dimethylformamide as catalyzer,toluene as solvent,reaction time: 6h,the yield achieved 88.7%, The appropriate reaction conditions of esterisy reaction: the proportion of Diethyl Malonate and 2,6-dichloro-5-fluoronicotinoyl chloride was 1.07:1. reaction time:2h,reaction temperature:50 ℃ . the yield achieved 82.1%, The appropriate reaction conditions of decarboxylation reaction: p-toluene sulfonylchloride as catalyzer,water as solvent, reaction time:10h, the yield achieved 57.1%, The appropriate reaction conditions of cyclization reaction:PH=9, DMF as solvent, reaction temperature:125℃. reaction time:lh .the yield achieved 95.1%.7-branched-chain's chemical name : 4-amiriomethyl-3-methyloxyiminopynolidin ,we improve and imagine the 7-branched-chain on the base of other people.The appropriate reaction conditions of cyclization reaction:Na as cyclization reagent, Isopropyl alcohol as initiator, reaction temperature:40℃. reaction time:3h. the yield achieved 57.1%.Jointing the two parts by means of the borate chelate first time,and choosing another solvent,and got a better yield. The appropriate reaction conditions of gemifloxacin: reactiontemperature:60°C. reaction time:5h, DMF as solvent,K2CC>3 as acid removal agent, the yieldachieved 43.7%The intermedias were characterized by IR spectra, MS spectra 'H-NMR spectra, the elemental analysis, the results showed that the structures of products were the same to the target compounds. The result prove that the route of the reaction is sound with better reactcondition.