To a chilled (ice-bath) solution of 369 mg (1.72 mmol) of 2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone in 10 mL of THF was added 70 mg (1.75 mmol) of 60% sodium hydride in mineral oil and the mixture was then chilled to −78° C. In another flask, to a chilled (−78° C.) solution of 508 mg (1.65 mmol) of 5-bromo-4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine (prepared according to the procedures in Misra, Bioorg. Med. Chem. Lett. 2003, 13, 2405, and Nakai in Chem. Pharm. Bull. 2004, 52, 1098) in 10 mL of anhydrous THF was added 670 μL (1.68 mmol) of a 2.5 M solution of n-BuLi in hexanes. The mixture stirred for 5 minutes and was then added to the sodium salt of 2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone. The reaction was monitored by TLC [ethyl acetate-hexanes (6:4)] indicating a new more polar product than both starting materials. After 1 hour, the mixture was diluted with 30 mL of saturated aqueous ammonium chloride and extracted with three 30 mL portions of ethyl acetate. The combined organic layers were washed with three 30 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane to load the sample and then eluting with ethyl acetate-hexanes (10-50% gradient) to afford 337 mg (44%) of title compound. Trituration with ether afforded 85 mg of the title compound as a white solid. MS m/z 444.38 (MH+).
