Tetrahydrofuran → 1-[3-Ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-yl]ethanone

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Reaction Steps

Methyltriphenylphosphonium bromide (4.64 g, 0.0130 mol) and lithium iodide (0.48 g, 0.0036 mot) were mixed in tetrahydrofuran (70 mL) in a 3-necked flask under an atmosphere of nitrogen. The flask was wrapped in aluminum foil to exclude light, and chilled to 0° C. n-Butyllithium (5.8 mL, 2.5 M in hexanes, 0.014 mol) was then added and the resulting mixture stirred for 30 minutes. A solution of 3-ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-carbonitrile (1.85 g, 7.22 mmol) in tetrahydrofuran (19.8 mL) was then added and the reaction stirred at 50° C. for 90 minutes. After cooling to room temperature, the product was extracted using dichloromethane (250 mL). The extract was washed brine and concentrated to afford the crude product as a semi-solid, which was purified by flash chromatography on silica gel using a 10-50% hexane:ethyl acetate gradient over 10 minutes (flow rate 20 mL/min). Concentration of the organics afforded 1.39 g (70.4%) of 1-[3-Ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-yl]ethanone as a colorless oil. LC/MS (EI) tR 3.72 (Method E), m/z 274.1 (M++1). All reagents were stored in a desiccator prior to use.

Provenance & Evidence