Phenol → (R)-4-(4,5-Dimethyl-6-phenoxy-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-carboxylic methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-carboxylic acid methyl ester (compound 54, 40 mg, 0.106 mmol) in 2 mL toluene is added phenol (45 mg, 0.48 mmol), potassium phosphate (40.6 mg, 0.19 mmol) and di-tbu X-Phos (5.3 mg, 0.014 mmol) in a 2 drum screw-top vial. The vial is evacuated and flushed with nitrogen, followed with the additon of palladium (II) acetate (2 mg, 0.01 mmol). The reaction mixture is flushed with nitrogen again and heated to 100° C. for 16 h. The mixture is filtered through Celite and the filtrate is concentrated to afford a brown oil. The crude product is purified by HPLC, eluting with 15-95% acetonitrile in water (both mobile phases modified with 3% n-PrOH) to provide the desired product as a white solid (9 mg, 22%).

Provenance & Evidence