161967-81-3

Raxar,Glaxo Wellcome,UK

Antibacterial.

Grepafloxacin Hydrochloride is a useful compound for treatment of ophthalmic and otic infections.

To 3-(3-methyl-1-piperazinyl)-4-fluoro-5-methyl-6-nitro-N-cyclopropylaniline is added diethyl ethoxymethylenemalonate and the mixture is heated at 150°C for 25 hours. After cooling, the reaction product is purified by silica-gel column-chromatography (dichloromethane:methanol = 100:1) to give diethyl[N-cyclopropyl-N-[3-(3-methyl-1-piperazinyl)-4-fluoro-5-methyl-6-nitrophenyl] aminomethylene]malonate. The product is dissolved in acetic anhydride and thereto conc. sulfuric acid is added dropwise at 50-60°C, followed by stirring for 30 min. The mixture is poured into ice-water, neutralized, extracted with dichloromethane and the extract is dried. The solvent is distilled off under reduced pressure. Purification by silica-gel column-chromatography (dichloromethane:methanol = 10:1) to give ethyl 7- (3-methyl-1-piperazinyl)-1-cyclopropyl-6-fluoro-5-methyl-1,4-dihydro-4- oxoquinoline-3-carboxylate. To these compound is 10% aqueous solution of sodium hydroxide and ethanol, and the mixture is refluxed for 1 hour. After cooling, the reaction mixture is diluted with water and washed with dichloromethane. The aqueous layer is made acidic with acetic acid and then made weakly alkaline with an aqueous sodium hydrogen carbonate. The product is extracted with dichloromethane and the extract is dried. The solvent is distilled off under reduced pressure and to the residue is added ethanol. The precipitated crystals are filtered and recrystallized from DMFA to give 7-(3-methyl-1-piperazinyl)-1-cyclopropyl-6-fluoro-5-methyl-1,4-dihydro- 4-oxoquinoline-3-carboxylic acid (12 mg), as white powder, m.p. 206-208°C.
7-(3-methyl-1-piperazinyl)-1-cyclopropyl-6-fluoro-5-methyl-1,4-dihydro-4- oxoquinoline-3-carboxylicacid may be transformed to hydrochloride.

Raxar (Otsuka).

Antibacterial

Store at -20°C