Sodium Chloride → Tetramethylurea

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A solution of 3-bromo-5-methylimidazo[1,2-a]pyridine-2-carboxylic acid hydrochloride (0.63 g, 2.2 mmol) (this material contained sodium chloride from the previous step) in N,N-dimethylformamide (6 mL) was treated with N,N-diisopropylethylamine (1.9 mL, 11 mmol) followed by O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and stirred at 20° C. for 5 min. The reaction mixture was treated with N,O-dimethylhydroxylamine hydrochloride (0.28 g, 2.8 mmol) and stirred at 20° C. for 2 h. The reaction mixture was poured into saturated sodium bicarbonate (100 mL) and extracted with ethyl acetate (100 mL). The aqueous phase was separated, saturated with sodium chloride, and extracted with additional ethyl acetate (100 mL). The combined organic extracts were washed with brine (100 mL), dried with sodium sulfate, filtered, and concentrated to a crude oil. Purification by flash column chromatography gave the desired product that also contained N,N-dimethylformamide and tetramethyl urea. This material was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (20 mL), dried with sodium sulfate, filtered, and concentrated to give 0.55 g of the desired product as a white solid. The aqueous layer, which still contained desired product, was concentrated and the resultant residue was purified by preparative LCMS to give an additional 42 mg of the desired product. The total amount isolated was 0.59 g (91%). LCMS for C11H13BrN3O2 (M+H)+: m/z=298.0, 300.0.

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