合成路线1

The condensation of 4-chloro-2,6-pyridinedicarboxylic acid (I) with morpholine (II) afforded the morpholinopyridinedicarboxylic acid (III), which was further esterified with MeOH and HCl to produce diester (IV). Reduction of (IV) with NaBH4 and CaCl2 gave hydroxy ester (V). After protection of the hydroxyl group of (V) as the trimethylsilylethoxymethyl derivative (VII), the ester group was hydrolyzed under basic conditions yielding acid (VIII). This was then subjected to a Curtius rearrangement with DPPA in the presence of tert-butanol to generate the tert-butyl carbamate (IX). Alkylation of carbamate (IX) with 3-methoxy-5-nitrobenzyl bromide (X) and NaH furnished the N-benzyl carbamate derivative (XI). The nitro group of (XI) was then reduced to amine (XII) by catalytic hydrogenation over Pd/C.