Ammonium Chloride → (1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2-methylsulfanyl-pyrimidin-5-yl)-methanol

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Reaction Conditions

Reaction Steps

To a solution of 1-benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (28, 8.40 g, 20.1 mmol) in 96.3 mL of tetrahydrofuran at −40° C. under nitrogen, isopropylmagnesium chloride (10.1 mL, 2.0 M in tetrahydrofuran, 20.3 mmol) is added slowly. The reaction is allowed to warm to 5° C. over 60 minutes, then cooled to −40° C., followed by addition of 2-methylsulfanyl-pyrimidine-5-carbaldehyde (34, 2.50 g, 16.2 mmol) in 15.0 mL of tetrahydrofuran. The reaction is allowed to warm to 10° C. over 2 hours, then poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with 40-100% ethyl acetate in hexane. Appropriate fractions are combined and the solvents removed under vacuum to provide the desired compound as an off-white solid (35, 4.0 g). MS (ESI) [M+H+]+=447.2.

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