Ethanol → HCID 68345601, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazine (510 mg, 2.1 mmol), DIPEA (700 μL, 4 mmol)), Pd[PhCN]2Cl2 (24 mg, 0.063 mmol), and 1,1-bis(diphenylphosphino)ferrocene (dppf) (48 mg, 0.087 mmol) in absolute ethanol (15 mL) is placed in a sealed pressure reactor with stirring and placed under 15 bars of carbon monoxide and warmed at 85° C. After 18 hours, the sealed pressure reactor is cooled to room temperature, returned to atmospheric pressure and opened. The reaction mixture is diluted with saturated aqueous ammonium chloride (30 mL) and extracted with EtOAc (3×20 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (2×15 mL) and brine (2×15 mL), dried over magnesium sulfate, filtered and concentrated. The crude product is passed through a pad of silica gel eluting using a gradient of 10-40% EtOAc in hexanes to afford 1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid ethyl ester as a solid.

Provenance & Evidence