Nicotinoyl chloride → N-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-nicotinamide

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Reaction Steps

In a reaction vial, N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-nicotinamide (37, 0.050 g, 0.21 mmol) is dissolved in 2 mL of dichloromethane. Aluminum trichloride (0.1 g, 1 mmol) and 2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (38, 0.075 g, 0.25 mmol) are added in one portion, and the reaction is stirred at room temperature for 36 hours, then diluted with water and extracted 3× with ethyl acetate. The organic layers are combined and washed 2× with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The amide linked at the 5-position is lost, so half the material is mixed with 3 mL of triethylamine in 2 mL of tetrahydrofuran and nicotinoyl chloride (36, 0.036 g, 0.25 mmol) is added and stirred at room temperature overnight. The reaction is diluted with water and extracted 3× with ethyl acetate. The organic layers are combined and washed 2× with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is further purified by reverse phase chromatography and the resulting material confirmed by LC-MS.

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