N,N'-Dimethylethylenediamine → 3-cyclohexyloxy-1-(4-fluoro-phenyl)-1H-pyrazin-2-one

Participants

Reaction Conditions

Reaction Steps

Copper (I) iodide (0.98 g, 5.1 mmol) was added to a suspension of 3-(cyclohexyloxy)-2(1H)-pyrazinone (1.0 g, 5.1 mmol, prepared according to the method described in the Journal of Medicinal Chemistry, 52(7), 2076-2089; 2009), 1-bromo-4-fluorobenzene (0.85 mL, 7.7 mmol), N,N′-dimethylethylenediamine (0.55 mL, 5.1 mmol) and K3PO4 (2.18 g, 10.3 mmol) in a mixture of DMF (2 mL) and 1,4-dioxane (8 mL). The reaction mixture was stirred at 180° C. for 15 minutes under microwave irradiation. The solid was filtered off and washed with DCM, the filtrate was treated with a 32% solution of NH4OH. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield 3-cyclohexyloxy-1-(4-fluoro-phenyl)-1H-pyrazin-2-one (1.13 g, 76% yield).

Provenance & Evidence