The condensation of 2-(2,4,5-trifluorobenzoyl)acetic acid ethyl ester (I) with cyclopropyl isothiocyanate (II) by means of NaH in DMF gives the sodium salt (IIIa-b), which is methylated with methyl iodide to afford the methylsulfanyl derivative (IVa-b). The cyclization of (IVa-b) by means of NaH in THF provides the methylsulfanyl quinolone (V), which is oxidized with MCPBA to the corresponding methylsulfinyl compound (VI). The reaction of (VI) with NaSH in THF furnishes 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII), which is cyclized with hydroxylamine-O-sulfonic acid and NaHCO3 through the intermediate (VIII), affording the isothiazoloquinoline (IX). Finally, this compound is condensed with piperazine (X) in pyridine to give the target compound.
The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V), which is finally condensed with piperazine in pyridine to furnish the target compound.
The cyclization of 2-(2,4-dichloro-3,5-difluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V), which is finally condensed with piperazine in pyridine to furnish the target compound.
The cyclization of 2-(2,4-dichloro-5-fluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V), which is finally condensed with piperazine in pyridine to furnish the target compound.