Bromine → N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide

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Reaction Steps

Potassium thiocyanate (4.44 g, 45.7 mmol) was suspended in acetic acid (100 mL), and the mixture was stirred at room temperature for 30 min. A solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide (4.1 g) in acetic acid (100 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 30 min. A solution of bromine (2.65 g, 16.6 mmol) in acetic acid (100 mL) was added dropwise to the obtained solution for 30 min or more. After the completion of the dropwise addition, the mixture was stirred at room temperature for 16 hr. The yielded yellow solid was filtered off, and washed with acetic acid, and the filtrate and the washing solution were combined and concentrated under reduced pressure. The residue was suspended in ethyl acetate (300 mL), and the suspension was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL×2) and saturated brine (100 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 (2.68 g, total of 2 steps 59%) as a yellow amorphous substance.

Provenance & Evidence