Potassium Carbonate → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,6-dichloropyridazine (20.1 g, 135 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (25.46 g, 122 mmol) and potassium carbonate (50.7 g, 367 mmol) in 1,4-dioxane (500 mL) and water (200 mL) under nitrogen was degassed by bubbling in nitrogen for 15 min. Dichlorobis(triphenylphosphine)palladium (II) (1.2%, 1 g, 1.4 mmol) was than added and nitrogen was bubbled in the mixture for another 10 min. The reaction mixture was stirred at 90° C. for 3 h, then cooled to room temperature and concentrated in vacuo to remove the majority of the 1,4-dioxane. The residue was partitioned between 1 N aqueous potassium carbonate (400 mL) and ethyl acetate (400 mL) and the phases separated. The aqueous layer was extracted with ethyl acetate (2×300 mL) and dichloromethane (300 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in-vacuo. The residue was stirred in diethyl ether (150 mL) and the orange precipitate was filtered and dried to return the title compound (12.76 g, 65.6 mmol, 54% yield). The filtrate was concentrated onto silica gel and purified by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate/hexane to return starting 3,6-dichloropyridazine as a white solid (9.9 g, 66.4 mmol, 49% yield).

Provenance & Evidence