Condensation of 3-fluoroaniline (I) with the cyclic anhydride (II) in AcOH gave amide (III). Subsequent cyclization of (III) in hot H2SO4 produced quinolineacetic acid (IV). After esterification of (IV) with methanol in the presence of SOCl2, the resulting methyl ester (V) was reduced to alcohol (VI) using NaBH4 in refluxing THF. Treatment of alcohol (VI) with SOCl2 afforded chloride (VII), which was condensed with 4-(1-piperazinyl)thieno[3,2-c]pyridine (VIII) yielding adduct (IX), isolated as the dihydro-chloride salt. Finally, alkylation of the quinoline N atom of (IX) with bromoacetamide (A) under phase-transfer conditions furnished the title compound.

Acylation of 3,4-difluoroaniline (VII) with Ac2O and Et3N afforded acetanilide (VIII). Subsequent condensation of (VIII) with the Vilsmeier reagent produced the quinolinecarbaldehyde (IX), which was reduced to alcohol (X) using NaBH4. Coupling of (X) with pyridinone (VI) under Mitsunobu conditions yielded adduct (XI). Finally, intramolecular Heck reaction in the presence of palladium diacetate and triphenylphosphine provided the desired pentacyclic compound.

Condensation of 3-fluoroaniline (I) with the cyclic anhydride (II) in AcOH gave amide (III). Subsequent cyclization of (III) in hot H2SO4 produced quinolineacetic acid (IV). After esterification of (IV) with methanol in the presence of SOCl2, the resulting methyl ester (V) was reduced to alcohol (VI) using NaBH4 in refluxing THF. Treatment of alcohol (VI) with SOCl2 afforded chloride (VII), which was condensed with 4-(1-piperazinyl)thieno[3,2-c]pyridine (VIII) yielding adduct (IX), isolated as the dihydro-chloride salt. Finally, alkylation of the quinoline N atom of (IX) with bromoacetamide (A) under phase-transfer conditions furnished the title compound.

Condensation of 3-fluoroaniline (I) with the cyclic anhydride (II) in AcOH gave amide (III). Subsequent cyclization of (III) in hot H2SO4 produced quinolineacetic acid (IV). After esterification of (IV) with methanol in the presence of SOCl2, the resulting methyl ester (V) was reduced to alcohol (VI) using NaBH4 in refluxing THF. Treatment of alcohol (VI) with SOCl2 afforded chloride (VII), which was condensed with 4-(1-piperazinyl)thieno[3,2-c]pyridine (VIII) yielding adduct (IX), isolated as the dihydro-chloride salt. Finally, alkylation of the quinoline N atom of (IX) with bromoacetamide (A) under phase-transfer conditions furnished the title compound.

The alkylation of 3-fluoroaniline (I) with 2-bromoacetamide (II) by means of KOH and Bu4NBr in THF gives 2-(3-fluorophenylamino)acetamide (III), which is condensed with 4-acetoxy-3,6-dihydro-2H-pyran-2,6-dione (IV) in Ac-OH to yield intermediate (V). The cyclization of (V) by means of H2SO4 or Ms-OH at 100?C affords the quinolone (VII), which is esterified with SOCl2 and methanol to provide the corresponding methyl ester (VII). The reduction of (VII) with NaBH4 in refluxing THF furnishes the 2-hydroxyethyl quinolone (VIII), which is treated with SOCl2 in refluxing CHCl3 to give the 2-chloroethyl derivative (IX). Finally, this compound is condensed with the arylpiperazine (X) by means of K2CO3 and KI in hot DMF to afford the desired quinolone.