合成路线1

Esterification of 2,6-difluoronicotinic acid (I) with methanol and sulfuric acid afforded methyl ester (II). This was treated with methylamine in DMF at 5 C to give a 2:1 mixture of the desired 6-methylaminonicotinate (III) and its regioisomer (IV), which were separated by column chromatography. Reaction of (III) with potassium methoxide generated from methanol and potassium tert-butoxide yielded methyl ether (V). Then, bromination with N-bromosuccinimide in DMF gave bromoester (VI), which was subsequently hydrolyzed with aqueous NaOH to provide acid (VII). Finally, the target amide was prepared by condensation of acid (VII) with the chiral amine (VIII) in the presence of carbonyldiimidazole.