The lithium dianion of 9-fluorenecarboxylic acid (I) was alkylated with 1,4-dibromobutane (II) to afford bromo acid (III). After conversion of (III) to the corresponding acid chloride by treatment with oxalyl chloride, condensation with 2,2,2-trifluoroethylamine furnished the intermediate bromo amide (IV).

The requisite nitrodiamine (VIII) was prepared via conversion of 4-methyl-1,2-phenylenediamine (V) to the selenocycle (VI) upon treatment with SeO2 and HCl, followed by nitration to afford regioselectively the nitro derivative (VII). Conversion to the diamine (VIII) was effected by treatment of (VII) with HI. Subsequent reaction of (VIII) with 2,4-pentanedione (IX) in the presence of HCl gave rise to the benzimidazole (X). Alkylation of (X) with bromide (IV) using K2CO3 in DMF provided adduct (XI) as the major regioisomer. Catalytic hydrogenation of the nitro group of (XI) then gave amine (XII). Finally, coupling of amine (XII) with 4'-(trifluoromethyl)biphenyl-2-carboxylic acid (XIII) was achieved via EDC activation or by previous conversion of (XIII) to the corresponding acid chloride with oxalyl chloride.

The lithium dianion of 9-fluorenecarboxylic acid (I) was alkylated with 1,4-dibromobutane (II) to afford bromo acid (III). After conversion of (III) to the corresponding acid chloride by treatment with oxalyl chloride, condensation with 2,2,2-trifluoroethylamine furnished the intermediate bromo amide (IV).

The requisite nitrodiamine (VIII) was prepared via conversion of 4-methyl-1,2-phenylenediamine (V) to the selenocycle (VI) upon treatment with SeO2 and HCl, followed by nitration to afford regioselectively the nitro derivative (VII). Conversion to the diamine (VIII) was effected by treatment of (VII) with HI. Subsequent reaction of (VIII) with 2,4-pentanedione (IX) in the presence of HCl gave rise to the benzimidazole (X). Alkylation of (X) with bromide (IV) using K2CO3 in DMF provided adduct (XI) as the major regioisomer. Catalytic hydrogenation of the nitro group of (XI) then gave amine (XII). Finally, coupling of amine (XII) with 4'-(trifluoromethyl)biphenyl-2-carboxylic acid (XIII) was achieved via EDC activation or by previous conversion of (XIII) to the corresponding acid chloride with oxalyl chloride.

The lithium dianion of 9-fluorenecarboxylic acid (I) was alkylated with 1,4-dibromobutane (II) to afford bromo acid (III). After conversion of (III) to the corresponding acid chloride by treatment with oxalyl chloride, condensation with 2,2,2-trifluoroethylamine furnished the intermediate bromo amide (IV).

The requisite nitrodiamine (VIII) was prepared via conversion of 4-methyl-1,2-phenylenediamine (V) to the selenocycle (VI) upon treatment with SeO2 and HCl, followed by nitration to afford regioselectively the nitro derivative (VII). Conversion to the diamine (VIII) was effected by treatment of (VII) with HI. Subsequent reaction of (VIII) with 2,4-pentanedione (IX) in the presence of HCl gave rise to the benzimidazole (X). Alkylation of (X) with bromide (IV) using K2CO3 in DMF provided adduct (XI) as the major regioisomer. Catalytic hydrogenation of the nitro group of (XI) then gave amine (XII). Finally, coupling of amine (XII) with 4'-(trifluoromethyl)biphenyl-2-carboxylic acid (XIII) was achieved via EDC activation or by previous conversion of (XIII) to the corresponding acid chloride with oxalyl chloride.