Collect. Czech. Chem. Commun. 1991, 56, 1937-1943

Structural modification and new methods for preparation of ofloxacin analogs

Stanislav Rádl, Lenka Kovářová, Jaroslav Moural and Radoslava Bendová

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Reaction of ethyl 2-(2,4-dichloro-5-fluoro-3-nitrobenzoyl)-3-ethoxyacrylate IIb with 2-amino-1-propanol provided corresponding compound IIIb which under alkaline conditions underwent an aromatic denitrocyclization reaction which after alkaline saponification provided 10-chloro-9-fluoro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid Vd. Treatment of 8-hydroxyquinolone VIII with 3-bromopropyne in the presence of sodium hydrogen carbonate provided methylene derivative VIIb which was saponified into a appropriate acid VIIc. Compound VIIb treated with N-methylpiperazine and then saponified yielded VIIa. Hydrogenation of 3-methylene derivative VIIb provided 3-methyl derivative Va.