1) The condensation of 2,4-dichloro-5-fluoro-benzoyl chloride (I) with diethyl malonate (II) by means of magnesium ethoxide gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate (III), which is partially decarboxylated with p-toluenesulfonic acid yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate (IV). The condensation of (IV) with triethyl orthoformate (V) by means of refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate (VI), which is treated with cyclopropylamine (VII) in ethanol giving ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(cyclopropylamino)acrylate (VII). The cyclization of (VII) by means of NaH in refluxing dioxane yields 1-cyclopropyl-7-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (IX), which is finally condensed with N-ethylpiperazine (X) by heating at 140 C in DMSO.
2) The condensation of quinoline (IX) with piperazine (XI) by heating at 140 C as before gives 1-cyclopropyl-6-fluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-3-carboxylic acid (XII), which is finally treated with ethyl iodide and triethylamine in hot DMF.
3) The condensation of 2,4-dichloro-5-fluorobenzoyl chloride (I) with methyl 3-(cyclopropylamino)acrylate (XIII) gives methyl 2-(2,4-dichloro-5-fluoro-benzoyl)-3-(cyclopropylamino)acrylate (XIV), which is first cyclized with t-BuOK and then hydrolyzed to give compound (IX).