合成路线1

Condensation of 3,4-difluoronitrobenzene (I) with an excess of piperazine (II) in refluxing acetonitrile yielded the 4-nitrophenylpiperazine (III), which was reduced to aniline (IV) by hydrogenation in the presence of Pd/C. Reaction with benzyl chloroformate provided the bis(carbamate) (V). This was treated with butyllithium at -78 C, and the resulting lithium salt was reacted with (R)-glycidyl butyrate (VI) to give chiral (R)-oxazolidinone (VII). Subsequent reaction with methanesulfonyl chloride, followed by displacement of the resulting mesylate with potassium phthalimide afforded the substituted phthalimide (VIII), which was deblocked with aqueous methylamine to give primary amine (IX). Further acetylation with Ac2O in pyridine yielded amide (IX) from which the N-carbobenzoxy group was removed by hydrogenolysis in the presence of Pd/C, providing the piperazine salt (XI). Then, alkylation of piperazine (XI) with 3-chloro-6-methylpyridazine (XII) in dimethylpropyleneurea (DMPU) at 90 C yielded the title compound.