Lithium Chloride → 3-(2,4-Difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-[1,2,4]triazine

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A mixture of 5-(3-bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine (from Example 8 below) (120 mg, 0.33 mmol), lithium chloride (70 mg), cuprous iodide (6.3 mg) and 3-fluoro-4-tributylstannylpyridine (120 mg, 0.31 mmol) in dry 1,4-dioxane (5 ml) was degassed under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (30 mg) was added and the mixture heated under an atmosphere of nitrogen at 80° C. for 48 h. On cooling to room temperature the mixture was partitioned between dichloromethane (30 ml) and 25% aqueous ammonium hydroxide (15 ml). The organic layer was separated, solvent removed at reduced pressure, and the residue subjected to preparative thin layer chromatography on silica gel, eluent 2% methanol in dichloromethane. The product was recrystallised from hot toluene to give 3-(2,4-difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-[1,2,4]triazine as a solid (50 mg): δH (500 MHz, d6-DMSO) 7.35 (1H, m), 7.52 (1H, m), 7.73 (2H, m), 8.34 (1H, m), 8.63 (3H, m), 8.78 (1H, s), 10.18 (1H, s); m/z (ES+) 383.

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