合成路线1

Lithiation of 2-bromopyridine (II) with BuLi, followed by addition to 1-phenylcyclopropanecarbonitrile (I), gave rise to ketone (III). Electrophilic nitration of the phenyl ring of (III) produced the nitro derivative (IV). The nitro group of (IV) was subsequently reduced by catalytic hydrogenation over Raney Ni to afford aniline (V), which was further acylated with trifluoroacetic anhydride, yielding amide (VI). A second nitration reaction in (VI) with HNO3-H2SO4 provided the nitro anilide (VII). Amide (VII) N-alkylation by means of iodomethane and K2CO3 gave the corresponding N-methyl derivative (VIII). The trifluoroacetamide function of (VIII) was then hydrolyzed under basic conditions to furnish the nitro aniline (IX), which was reduced to the phenylenediamine (X) by catalytic hydrogenation in the presence of Raney Ni. Acylation of (X) by N-(4-cyanophenyl)glycine (XI) yielded amide (XII). Benzimidazole (XIII) was then obtained by cyclization of (XII) in refluxing HOAc. The keto group of (XIII) was converted to the oxime derivative (XV) by condensation with ethyl (aminooxy)acetate (XIV). Finally, Pinner reaction of nitrile (XV) with ethanolic HCl, followed by treatment of the resulting imidate with ammonium carbonate provided the target amidine.