Bromine → N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)(methyl)amino]-2-fluorophenyl)-2,2,2-trifluoroacetamide

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Reaction Steps

Potassium thiocyanate (2.96 g, 30.5 mmol) was suspended in acetic acid (20 mL), and the suspension was stirred at room temperature for 10 min. To the obtained solution was added N-{5-[(5-aminopyridin-2-yl)(methyl)amino]-2-fluorophenyl}-2,2,2-trifluoroacetamide (2.0 g, 6.96 mmol), and the mixture was further stirred at room temperature for 10 min. The obtained solution was slowly added dropwise to a solution of bromine (1.17 g, 7.30 mmol) in acetic acid (10 mL). After the completion of the dropwise addition, the mixture was stirred at room temperature for 20 hr. The resultant black insoluble material was filtered off, and washed with acetic acid. The combined filtrate and washing were concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (100 mL), washed with saturated aqueous sodium hydrogen carbonate solution (70 mL) 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. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (1.00 g, 43%) as a colorless powder.

Provenance & Evidence