Potassium thiocyanate (536 mg, 5.52 mmol) was suspended in acetic acid (10 mL), and the mixture was stirred at room temperature for 10 min. A solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-cyanophenyl}-3-(1-cyano-1-methylethyl)benzamide (550 mg, 1.38 mmol) in acetic acid (10 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 10 min. A solution of bromine (242 mg, 1.51 mmol) in acetic acid (7 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 the washing fluid were combined, and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (100 mL), and the suspension was washed with 5% aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 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). The obtained solution was concentrated under reduced pressure to give the title compound (0.51 g, 81%) as a pale-yellow amorphous substance.
