Methyl iodide → 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine

Participants

Reaction Steps

7-Iodo-2H-pyrazolo[4,3-b]pyridine (100 mg, 0.408 mmol), iodomethane (0.025 ml, 0.408 mmol) and cesium carbonate (266 mg, 0.816 mmol) were combined in DMF (5 mL). The mixture was stirred at room temperature for 1 hour then purified by preparative HPLC eluting with a gradient of 20-70% 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water using a Phenomenex Gemini Prep 5 μm C18, 75×30 mm column to give 7-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 14.19% yield) and 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine (30 mg, 28.4% yield). MS [M+H] found 260.0. 7-Iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 0.058 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.326 mg, 1.448 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.38 mg, 0.014 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (11.77 mg, 0.058 mmol) and sodium 2-methylpropan-2-olate (16.69 mg, 0.174 mmol) were combined in dioxane (5 mL). The mixture was heated at 120° C. for 2 hours and then purified by preparative HPLC eluting with a gradient of 5-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to afford the title compound as a TFA salt.

Provenance & Evidence