Trifluoroacetic acid → 6-Bromo-2-trifluoromethyl-3H-imidazo[4,5-b]pyridine

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Reaction Steps

A solution of 5-bromopyridine-2,3-diamine (100 mg, 0.53 mmol) in trifluoroacetic acid (20 mL) and hydrochloric acid (4 mL) was stirred overnight at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum and dissolved in water (100 ml), adjusted to pH 8 with sodium carbonate and extracted with ethyl acetate (3×80 ml). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to produce 6-bromo-2-(trifluoromethyl)-1H-imidazo[4,5-b]pyridine as a brown solid (200 mg, crude). To a solution of (4-chlorophenyl)boronic acid (117 mg, 0.75 mmol) in water (5 mL) and dioxane (15 mL) was added 6-bromo-2-(trifluoromethyl)-1H-imidazo[4,5-b]pyridine (100 mg, crude), Pd(PPh3)4 (43.4 mg, 0.04 mmol) and sodium carbonate (119.5 mg, 1.13 mmol). The resulting solution was stirred overnight at 100° C. with an inert atmosphere of nitrogen and then concentrated under vacuum. The residue was dissolved in water (50 mL), extracted with ethyl acetate (4×50 mL), the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (60 mg) was purified by Prep-HPLC to produce 6-(4-chlorophenyl)-2-(trifluoromethyl)-1H-imidazo[4,5-b]pyridine. TFA salt as a white solid (30 mg).

Provenance & Evidence