合成路线1

The methylation of 1-bromo-2,4,5-trifluoro-3-(trimethylsilyl)benzene (I) with methyl trifluoromethylsulfonate (II) by means of diisopropylamine and butyllithium in THF gives 2-bromo-3,5,6-trifluoro-4-(trimethylsilyl)toluene (III), which is carbonated with butyllithium and CO2 in ether to yield 2,4,5-trifluoro-6-methyl-3-(trimethylsilyl)benzoic acid (IV). Elimination of the silyl group with CsF in acetonitrile affords the corresponding benzoic acid (V). The condensation of (V) with malonic acid monoethyl ester (VI) by means of oxalyl chloride and butyllithium in THF affords 3-(3,4,6-trifluoro-2-methylphenyl)-2-oxopropionic acid ethyl ester (VII), which by condensation with triethyl orthoformate in refluxing acetic anhydride is converted into the ethoxymethylene derivative (VIII). The cyclization of (VIII) with cyclopropylamine (IX) by means of sodium hydride in THF gives 1-cyclopropyl-6,7-difluoro-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (X), which is hydrolyzed with refluxing 6N HCl to yield the corresponding free acid (XI) (1). Finally, this compound is condensed with 2-methylpiperazine (XII) by means of triethylamine in refluxing acetonitrile.