3-(Trifluoromethyl)benzoic acid → HCID 58349020, compound

Participants

Reaction Steps

To a solution of N-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-yl]cyclopropanecarboxamide (200 mg, 620 μmol) in pyridine (5 mL) were added 3-(trifluoromethyl)benzoic acid (241 mg, 1.27 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (479 mg, 2.50 mmol) and N,N-dimethylpyridine-4-amine (28.3 mg, 232 μmol), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture were added methanol (2 mL) and 8N aqueous sodium hydroxide solution (2 mL), and the mixture was further stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (50 mL) and methanol (1 mL). This solution was washed with water (50 ml), 0.1N hydrochloric acid (50 mL) and saturated aqueous sodium hydrogencarbonate solution (50 mL), successively, and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (ethyl acetate/hexane=2/98→80/20), and further purified by reversed phase silica gel column chromatography (containing 0.1% trifluoroacetic acid, water/acetonitrile=95/5→0/100). The fraction containing the object product was concentrated, and the residue was dissolved in ethyl acetate (50 mL) and methanol (10 mL). The mixture was washed with saturated aqueous sodium hydrogencarbonate solution (50 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated. The obtained residue was recrystallized from acetone and diisopropyl ether to give the title compound (139 mg, 45%) as colorless crystals.

Provenance & Evidence