Delafloxacin is a fluoroquinolone antibacterial drug that can be used to treat acute bacterial skin and skin structure infections.The synthetic process in this article is referenced from the relevant literatures.Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate(12)was condensed with triethylorthoformate to give ethyl(Z)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxyacrylate(13).This intermediate was directly treated with 2,6-diamino-3,5-difluoropyridine(2)to give ethyl(Z)-3-((6-amino-3,5-difluoropyridin-2-yl)amino)-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate(18).Treatment of 18 with lithium chloride in N-methylpyrrolidone(NMP)followed by reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)provided cyclization to ethyl 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate(19).Intermediate 19 was treated with 3-hydroxyazetidine hydrochloride(5)and DBU to give ethyl 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate(20).Hydrolysis of the intermediate 20 gave delafloxacin(9).Salt formation with N-methyl-D-glycamine provided delafloxacin meglumine(11)with a purity of 99.94％(HPLC)and an overall yield of 61.2％(based on compound 12).The improved process has the advantages of simple operation,low cost and suitable for industrialisation.
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