Bromine → Methyl 3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-methoxybenzoate

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Reaction Steps

To a suspension of potassium thiocyanate (12.1 g, 125 mmol) in acetic acid (100 mL) was added a solution of methyl 3-[(5-aminopyridin-2-yl)oxy]-4-methoxybenzoate (26.7 mmol) in acetic acid (100 mL), and the mixture was stirred at room temperature for 15 min. The obtained solution was cooled to 0° C., a solution of bromine (6.55 g, 41.0 mmol) in acetic acid (80 mL) was added dropwise for 1 hr or more. After the completion of the dropwise addition, the mixture was stirred for 16 hr, during which the reaction temperature was allowed to gradually warm to room temperature. The yielded yellow solid was filtered off, and washed with water. The filtrate and the washing solution were combined, and concentrated under reduced pressure, and the residue was treated with saturated aqueous sodium hydrogen carbonate solution (200 mL). The obtained solution was extracted with ethyl acetate (100 mL×6), and the combined organic layer was dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (6.0 g, total of 3 steps 67%) as a pale-brown solid.

Provenance & Evidence