Sodium hydride → N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine

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Reaction Steps

Sodium hydride (1.732 g, 41.13 mmol) was added to N-(1,3-dimethylpyrazol-4-yl)acetamide (6.3 g, 41.1 mmol) dissolved in THF (80 mL) under nitrogen. The resulting light suspension was stirred at room temperature for 15 minutes then at 35° C. for 15 minutes and then 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (6.02 g, 19.6 mmol) was added. The mixture was stirred at 35° C. for 20 minutes then at 45° C. for 30 minutes, giving a light purple solution. The resulting mixture was allowed to cool to room temperature, quenched with water (30 mL) and lithium hydroxide hydrate (2.466 g, 58.75 mmol) was added. The mixture was stirred at room temperature for 1.5 hours. The mixture was extracted twice with DCM. The combined organic phases were washed with water, brine, dried over magnesium sulfate and concentrated to afford the crude product. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% EtOAc in DCM. The fractions containing pure product were evaporated to dryness, sonicated in petroleum ether then collected by filtration, washed with petroleum ether and dried to a constant weight to afford N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (3.5 g, 9.16 mmol, 46.8%) as a white solid.

Provenance & Evidence