Triethylamine → 3-(1-cyanocyclopropyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide

Participants

Reaction Steps

To a solution of N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide (436 mg, 1.02 mmol) produced in Example A15(iii) in pyridine (10 mL) were added (4-methylpiperazin-1-yl)acetic acid dihydrochloride (278 mg, 1.20 mmol), N,N-dimethylpyridine-4-amine (79.3 mg, 649 μmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (470 mg, 2.45 mmol) at room temperature, and the mixture was stirred at room temperature for 14 hr. To the reaction mixture were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (454 mg, 2.37 mmol), (4-methylpiperazin-1-yl)acetic acid dihydrochloride (281 mg, 1.22 mmol), and triethylamine (10 mL) and the mixture was further stirred for 4 hr. To the reaction mixture was added methanol (10 mL) and the mixture was stirred at room temperature for 30 min and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL), washed with saturated aqueous ammonium chloride solution (80 mL×2) and saturated aqueous sodium hydrogencarbonate solution (50 mL), successively, 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 silica gel column chromatography (ethyl acetate/methanol=100/0→90/10) and crystallized from ethyl acetate and hexane to give the title compound (136 mg, 24%) as colorless crystals.

Provenance & Evidence