2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol

Participants

Reaction Steps

To a chilled (−78° C.) (dry ice-acetone) solution of 291 mg (1.0 mmol) of 5-bromo-1-(4-fluorophenyl)-1H-indazole in 5 mL of anhydrous THF was added rapidly 0.4 mL (1.0 mmol) of a 2.5 M solution of n-butyllithium (n-BuLi) in hexanes. Immediately after, a chilled (dry ice-acetone bath) solution of 2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone (prepared according to the procedure described in J. Org. Chem. 2002, 76, 6226) in 3 mL of THF was added rapidly. The mixture stirred for 1 hour, TLC [ethyl acetate-hexanes (1:1)] indicated a new more polar product than both starting materials. The mixture was diluted with 10 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 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-CH2Cl2 (0-30% gradient). The material from the column was solidified from ether-hexanes (1:1), dried under house vacuum at 90° C. for 3 hours, to afford 91 mg (42%) of the title compound. MS m/z 427.18 (MH+).

Provenance & Evidence