Dimethylformamide → HCID 178512319, compound

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Reaction Steps

1-(2,5-Bistrifuoromethylphenyl)-2-(benzimidazol-2-yl)ethylamine. To a stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.91 mL, 13.8 mmol, 1.11 equiv) in 13 mL anhydrous THF at 0° C. was added n-butyllithium (5.20 mL of a 2.5 M solution in hexane, 13.0 mmol, 1.05 equiv). After 15 min, 2,5-bistrifluoromethylbenzaldehyde (2.04 g, 8.43 mmol) in anhydrous THF (4 mL) at 0° C. was slowly added, followed by chlorotrimethylsilane (1.73 mL, 1.6 mmol, 1.10 equiv). The mixture was partitioned between EtOAc and water, and the organic layer was washed with brine (3×50 mL), dried (Na2SO4), and concentrated to give Compound A as a solid. B. N-(2,4-Dichlorophenyl)-N′-[1-(2,5-bistrifluoromethylphenyl)-2-(imidazol-1-yl)-ethyl]-N″-cyanoguanidine. To a stirred solution of 1-(2,5-bistrifuoromethylphenyl)-2-(imidazol-1-yl)ethylamine (1.1 g, 3.4 mmol) in DMF at rt, N-cyano-N′-(2,4-dichlorophenyl)thiourea (1.1 g, 4.1 mmol) was added, followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (800 mg, 4.1 mmol). The mixture was allowed to stir at rt for 18 h and then partitioned between EtOAc and saturated ammonium chloride solution. The organic layer was separated and washed with saturated ammonium chloride solution (3×50 mL). The organic layer was dried and concentrated, and the residue was purified by silica gel column chromatography (EtOAc, MeOH, NH4OH; 95:5:0.1) to give a solid (350 mg). MS (ES): m/z 535 [M+H]+.

Provenance & Evidence