合成路线1

Esterification of 3-methyl-2-nitrobenzoic acid (I) with MeOH in the presence of AcCl at reflux gives methyl 3-methyl-2-nitrobenzoate (II), which is then brominated with NBS in the presence of (PhCO)2O2 in refluxing CCl4 to yield methyl 3-(bromomethyl)-2-nitrobenzoate (III). Oxidation of the bromo derivative (III) with NMMO in acetonitrile leads to methyl 3-formyl-2-nitrobenzoate (IV), which is then condensed with 4-(N-Boc-3-piperidinyl)aniline (V) in refluxing EtOH to afford the corresponding imine (VI). Ring closure of the imine derivative (VI) by means of NaN3 in DMF at 90 °C provides the indazole derivative (VII), which is then treated with NH3 in MeOH at 60 °C to give the carboxamide derivative (VIII). Deprotection of compound (VIII) by means of HCl leads to the hydrochloride salt of the corresponding amine, which is finally resolved by chiral supercritical fluid chromatography (chiral SFC) and treated with HCl .
Aldehyde intermediate (IV) can be prepared in a large-scale synthesis by treatment of methyl 3-methyl-2-nitrobenzoate (II) with DMFA in DMF at 130 °C to give enamine (X), which is finally oxidized with NaIO4 in DMF/H2O .