p-Toluenesulfonic acid → Ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate

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Reaction Steps

A solution of 2-chloro-4-(trifluoromethyl)pyrimidine (42 mg, 0.23 mmol), ethyl 1-[4-(3-aminophenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate (76 mg, 0.23 mmol) and 4-methylbenzenesulfonic acid (44 mg, 0.23 mmol) in dioxane (1 mL) was heated to 100° C. overnight. After cooling to room temperature the reaction was concentrated under reduced pressure. The resulting residue was diluted with 30 mL ethyl acetate and washed with 30 mL saturated aqueous sodium bicarbonate and 30 mL brine. The aqueous layers were further extracted with 30 mL ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. Purification by CombiFlash (10-50% ethyl acetate/hexanes) provided 38 mg (0.08 mmol, 35% yield) of ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate as a white solid.

Provenance & Evidence