The condensation of 4-fluoro-3-nitrobenzoic acid (I) with 1-methylpiperazine (II) by means of oxalyl chloride in dichloromethane gives the expected acyl derivative (III), which is reduced with BH3/THF to yield the benzyl piperazine (IV). The condensation of (IV) with 2(R)-hydroxy-2-phenylethylamine (V) by means of DIEA in NMP affords the secondary amine (VI), which is reduced with H2 over Pd/C in ethanol, providing the phenylenediamine (VII). Finally, this compound is cyclized with 4-methoxybenzoyl isothiocyanate (VIII) by means of EDC in DMF to furnish the target benzimidazole.

Alternatively, the reduction of 4-fluoro-3-nitrobenzoic acid (I) with BH3/THF gives the benzyl alcohol (IX), which is treated with PBr3 in ethyl ether to yield the benzyl bromide (X). Finally, this compound is condensed with 1-methylpiperazine (II) by means of DIEA in THF to afford the already reported benzyl piperazine intermediate (IV).

The reduction of 4-fluoro-3-nitrobenzoic acid (I) with BH3/THF gives the benzyl alcohol (IX), which is condensed with 2(R)-hydroxy-2-phenylethylamine (V) by means of DIEA in NMP to yield nitro compound (XI). Derivative (XI) is then converted into secondary amine (XII) by reduction either with H2 over Pd/C in EtOH or with Na2S?H2O in dioxane/H2O or by treatment with Na2S2O4 in dioxane/NH4OH. Cyclization of (XI) with 4-methoxybenzoyl isothiocyanate (VIII) by means of EDC in DMF affords the benzimidazole (XIII), which is oxidized at the carbinol group by means of MnO2 in THF to provide the corresponding carbaldehyde (XIV). Finally, this compound is reductocondensed with 1-methylpiperazine (II) by means of NaBH(OAc)3 to furnish the target benzimidazole.