Stille reaction

A mixture of 4-methyl-5-(tributylstannanyl)pyridazine (1.0 g, 2.64 mmol), 1 ,1-dimethylethyl 4- {(1 S)-1-[(5-bromo-2-pyrazinyl)oxy]ethyl}-1-piperidinecarboxylate (600 mg, 1.55 mmol), bis(triphenylphosphine)palladium(ll) chloride (109 mg, 0.155 mmol) and copper(l) iodide (59 mg, 0.31 mmol) in DMF (7 mL) was degassed with nitrogen for 15 min. The mixture was stirred in a microwave at 140°C for 30 min, cooled to room temperature, poured onto a 10% KF (aq) solution, then diluted with EtOAc, and stirred at room temperature for 1 h. The mixture was extracted with EtOAc. The organics were pooled, filtered through a ChemElut (10 mL) column, and eluted with EtOAc. The organics were concentrated to dryness and the resulting residue was purified by chromatography on an amino-silica gel column using 0 to 30% EtOAc/hexanes gradient to give the title compound (609 mg, 98%) as an orange solid.


Patent reference: WO2010014593 (GSK)