1-Methyl-3-(trifluoroacetyl)-1H-indole → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-2-methyl-1H-benzimidazol-5-yl]-1-(1-methyl-1H-indol-3-yl)ethanol

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Reaction Steps

To a chilled (−78° C.) solution of 5-bromo-1-(4-fluorophenyl)-2-methyl-1H-benzimidazole (210 mg, 0.68 mmol) in anhydrous THF (3 mL) was added n-butyllithium (1 mmol, 400 μL of a 2.5 M solution in hexanes) over a 1 minute period followed by a chilled (−78° C.) solution of 2,2,2-trifluoro-1-(1-methyl-1H-indol-3-yl)ethanone (200 mg, 0.88 mmol) in 1 mL of anhydrous THF. After 30 minutes, the mixture was quenched with ammonium chloride solution and extracted with methylene chloride. The organic layer was concentrated to afford a yellow oil. The residue was purified by column chromatography over silica gel eluting with 0-50% ethyl acetate in hexanes. The product rich fractions were collected and concentrated in vacuo to afford a light yellow oil. A second purification by reverse phase HPLC (C-18 column) using a gradient of 20-100% acetonitrile (0.1% TFA) in water (0.1% TFA) over 15 minutes and fractions corresponding to an earlier eluting peak (M+H 455) were collected. The acetonitrile was concentrated in vacuo, the residue was made basic with aqueous sodium bicarbonate, and extracted with methylene chloride. The organic layer was concentrated to afford 55 mg of the title compound as an off-white solid. MS m/z 455 (MH+).

Provenance & Evidence