合成路线1

Condensation of the anion resulting from 2-fluoro-4-methylpyridine (I) and LDA with N-methoxy-N-methyl-3-trifluoromethylbenzamide (II) afforded ketone (III). Subsequent alpha-oximination of (III) with tert-butyl nitrite and HCl provided the required E-oxime (IV) as the major isomer. Cyclization of (IV) with N-(benzyloxycarbonyl)piperidine-4-carboxaldehyde (V) and ammonium acetate in refluxing AcOH afforded hydroxyimidazole (VI). Further reduction of (VI) to imidazole (VII) was carried out with titanium trichloride. Methylation of the imidazole ring of (VII) by treatment with N,N-dimethylformamide dimethylacetal in boiling toluene gave rise to a mixture of both N-methylated imidazoles, from which the desired compound (VIII) was isolated by column chromatography as the minor isomer. Nucleophilic displacement of the fluoropyridine of (VIII) by (S)-alpha-methylbenzylamine (IX) at 150 C gave the corresponding aminopyridine derivative (X). The N-benzyloxycarbonyl protecting group was finally removed by catalytic hydrogenation over Pd/C.