Sodium Hydroxide → N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}phenoxy)-1,3-benzothiazol-2-yl]-1,3-oxazole-4-carboxamide

Participants

Reaction Steps

To a solution of N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide (330 mg, 774 μmol) in pyridine (10 mL) were added 1,3-oxazole-4-carboxylic acid (120 mg, 1.06 mmol), N,N-dimethylpyridine-4-amine (52.3 mg, 428 μmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (220 mg, 1.15 mmol), and the mixture was stirred at room temperature for 12 hr. To the reaction mixture were added 1,3-oxazole-4-carboxylic acid (126 mg, 1.11 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (652 mg, 3.40 mmol) and the mixture was further stirred at room temperature for 16 hr. To the reaction mixture were added methanol (10 mL) and 2N aqueous sodium hydroxide solution (5 mL) and the mixture was stirred at the same temperature for 3 hr, and the solvent was evaporated under reduced pressure. The residue was diluted with ethyl acetate (50 mL), washed with water (50 mL), 0.1N hydrochloric acid (50 mL), and saturated aqueous sodium hydrogencarbonate solution (50 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by reversed phase silica gel column chromatography (containing 0.1% trifluoroacetic acid, water/acetonitrile=95/5→5/95) and concentrated. The obtained trifluoroacetate was suspended in ethyl acetate (100 mL) and methanol (10 mL), and washed with saturated aqueous sodium hydrogencarbonate solution (50 mL) and saturated brine (50 ml), successively. The organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off and the filtrate was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate and diisopropyl ether to give the title compound (156 mg, 34%) as colorless crystals.

Provenance & Evidence