HCID 57963046, compound → {6-fluoro-5-[hydroxy-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To 3-iodo-5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (8, 40 g, 97.0 mmol) in 400 mL of tetrahydrofuran under an atmosphere of nitrogen at −20° C., isopropylmagnesium chloride (54.8 mL, 2 M in tetrahydrofuran, 110 mmol) is added and the reaction allowed to warm to 0° C. over 30 minutes. The reaction is cooled to −40° C. and (6-fluoro-5-formyl-pyridin-2-yl)-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (47, 15.81 g, 43.9 mmol) in tetrahydrofuran is added. The reaction is allowed to warm to 0° C. over an hour, then quenched with brine and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 0-40% ethyl acetate in hexane. Appropriate fractions are combined and the solvents removed under vacuum to provide the desired compound (48, 21 g, 32.4 mmol, 73.8% yield).

Provenance & Evidence