N,O-Dimethylhydroxylamine → 2-amino-5-bromo-N-methoxy-N-methylnicotinamide

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Reaction Steps

To a solution of 2-amino-5-bromonicotinic acid (7 g, 32.3 mmol), N,O-dimethylhydroxylamine (5.99 g, 61.37 mmol) in N-methylmorpholine (60 ml) and dichloromethane (500 ml) at 0° C. was added PyBop (25.2 g, 48.45 mmol) portionwise. The solution was allowed to warm to room temperature and the mixture was stirred at room temperature for 18 hours. The reaction mixture was washed with a 2M aqueous solution of NaOH and with a 10 wt % solution of citric acid. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was dissolved in ether and the formed solid was filtered off. The mother liquors were concentrated in vacuo to approximatively half of the original volume. This solution was diluted with dichloromethane and stirred vigorously while adding a 2M HCl solution in diethylether until complete formation of the precipitate. The solid was filtered off and partitioned between a 2M aqueous solution of NaOH and EtOAc. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to dryness to afford the title compound as a cream solid (5.26 g, 63% yield).

Provenance & Evidence