1,2-Dichloroethane → HCID 178457801, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of cis-N-isopropyl-4-(2-nitro-5-(1H-1,2,4-triazol-1-yl)phenylamino)-cyclohexanecarboxamide (100 mg, 0.269 mmol) in EtOH (3 mL) was added tin(II) chloride dihydrate (242 mg, 1.074 mmol). The reaction was stirred at 80° C. After 3 hours, another four equivalents of tin(II) chloride dihydrate (242 mg, 1.074 mmol) was added, and the reaction was stirred at 80° C. for an additional 3 hours, and then at RT overnight. The reaction mixture was concentrated, and the residue was partitioned between EtOAc and 1 N aqueous sodium hydroxide. The aqueous layer was extracted with EtOAc; the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The diamine was dissolved in THF (3 mL), cooled to 0° C., and 4-fluorobenzoyl isothiocyanate (53.5 mg, 0.296 mmol) was added. The reaction was stirred at 0° C. for 30 minutes, then DIPEA (0.070 mL, 0.403 mmol) and EDC (77 mg, 0.403 mmol) were added, and the reaction was stirred for 1 hour at 60° C. The residual material was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 20-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(1H-1,2,4-triazol-1-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as an off-white powder (44 mg, 33.5% yield). MS, m/z (C26H28FN7O2): Calc'd, 489.2. found, 489.9 [M+H].

Provenance & Evidence