Toluene → 6-methyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromo-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one (Example 128) (0.1 g, 0.28 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (61.5 mg, 84.0 μmol) and N,N-dimethylethanolamine (14.1 μL, 140 μmol) in tetrahydrofuran (1.5 mL) under argon was treated with 1.2M dimethylzinc in toluene (280 μL, 0.33 mmol). The reaction mixture was stirred in a sealed vial at 50° C. overnight. At this time, the reaction was treated with additional dimethylzinc (0.14 mL). The reaction mixture was stirred at 50° C. over the weekend. At this time, the reaction mixture was cooled to room temperature, quenched with a saturated aqueous ammonium chloride solution and then extracted with ethyl acetate. Methanol (0.5 mL) was added, the mixture was filtered and the layers were separated. The organic layers were absorbed onto silica gel. Flash chromatography (12 g silica column, 0-40% ethyl acetate/hexanes) followed by trituration with methylene chloride afforded 6-methyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one (14 mg, 17%) as white solid. 1H NMR (methanol-d4) δ ppm 7.76-7.86 (m, 4H), 7.69 (s, 1H), 7.28 (s, 1H), 6.95, (s, 1H), 2.28 (s, 3H). LC-MS calcd. for C15H12F3N2O [(M+H)+] 293, obsd. 293.1.

Provenance & Evidence