3-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine → 5-Chloro-2-{5-fluoro-4-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-2-methoxy-phenoxymethyl}-benzimidazole-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

3-Iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 0.200 g, 0.5 mmol, prepared as described in Example 22) was dissolved in tetrahydrofuran (3 mL, 40 mmol). After the reaction reached the temperature of −20° C., a solution of 2M of isopropylmagnesium chloride in tetrahydrofuran (300 μL) was added dropwise. The resulted mixture was stirred to −5° C. After cooling the reaction to −20° C., a solution of 6-chloro-2-(5-fluoro-4-formyl-2-methoxy-phenoxymethyl)-benzoimidazole-1-carboxylic acid tert-butyl ester (152, 0.2 g, 0.46 mmol) in tetrahydrofuran (4 mL) was added at once to the mixture. The reaction warmed to −5° C. and was then evaporated to dryness under reduced pressure. Ethyl acetate was added. The organic portion was washed with saturated sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated. Purification with silica gel flash chromatography eluting with a gradient of ethyl acetate (5 to 80%) in hexanes gave the desired compound (153, 0.142 g, 44%). MS (ESI) [M+H+]+=709.4.

Provenance & Evidence