Potassium thiocyanate (972 mg, 10 mmol) was suspended in acetic acid (20 mL), and the mixture was stirred at room temperature for 10 min. A solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide (1.0 g, 2.50 mmol) in acetic acid (20 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 15 min. A solution of bromine (439 mg, 2.75 mmol) in acetic acid (14 mL) was slowly added dropwise to the obtained solution. After the completion of the dropwise addition, the mixture was stirred at room temperature for 12 hr. The yielded yellow insoluble material was filtered off, and washed with acetic acid. The filtrate and washing solution were combined and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (250 mL), and the suspension was washed with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (1.0 g, 87%) as a pale-yellow amorphous substance.
