Bromine → N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-fluorophenyl}-2-chloro-3-(1-cyano-1-methylethyl)benzamide

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Reaction Steps

To a solution of potassium thiocyanate (1.65 g, 17.0 mmol) in acetic acid (15 mL) was added a solution of N-[3-(4-aminophenoxy)-4-fluorophenyl]-2-chloro-3-(1-cyano-1-methylethyl)benzamide (1.75 g, 4.13 mmol) in acetic acid (5 mL), and the mixture was stirred at room temperature for 15 min. To the obtained solution was added dropwise a solution of bromine (726 mg, 4.54 mmol) in acetic acid (15 mL) at room temperature over 30 min or longer. After the completion of the dropwise addition, the mixture was stirred at room temperature for 4 hr. The resulting yellow solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL) and ethyl acetate (200 mL), and basified with 2N aqueous sodium hydroxide solution. The aqueous layer was separated, and the organic layer was washed with saturated aqueous ammonium chloride solution (200 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (854 mg, 43%) as a yellow amorphous substance. The obtained compound was used in the next reaction without a further purification.

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