合成路线1

Esterification of L-pyroglutamic acid (I) using SOCl2 in MeOH, followed by protection of the resulting methyl ester (II) with Boc2O and DMAP in acetonitrile affords N-Boc-L-pyroglutamic acid methyl ester (III). Subsequent treatment of pyroglutamate (III) with Bredereck’s reagent in hot DME yields the [(dimethylamino)methylene]pyrrolidinone (IV), which is diastereoselectively reduced to the 4(S)-methyl derivative (V) by catalytic hydrogenation over Pd/C. Further reduction of the amide and ester groups of compound (V) using in situ-generated Ca(BH4)2 in EtOH/MTBE furnishes diol (VI), which is converted to the bis-mesylate (VII) under the usual conditions. The bis-mesylate (VII) is then cyclized with benzylamine in refluxing dimethoxyethane followed by catalytic hydrogenolysis of the resulting N-benzylpiperidine (VIII) to provide 3(S)-Boc-amino-5(S)-methylpiperidine (IX). Coupling of the protected aminopiperidine (IX) with the fluoroquinolone boron chelate (X) in the presence of Et3N in hot acetonitrile affords, after alkaline decomplexation, the piperidinyl quinolone (XI), which is finally deprotected by treatment with HCl in CH2Cl2 (1, 2). Scheme 1.