Methyl iodide → HCID 56942725, compound

Participants

Reaction Steps

To a solution of 2-N-(3-Chloro-4-fluorophenyl)-6-{5-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine (Example 413, 0.049 g, 0.101 mmol) in DMF (1 mL) was added potassium carbonate (0.028 g, 0.028 mmol) and iodomethane (0.021 g, 0.152 mmol). The reaction mixture was stirred at room temperature for 14 h after which time further iodomethane (0.042 g, 0.304 mmol) was added and the mixture was stirred at room temperature for 56 h. LCMS indicated incomplete conversion so further iodomethane (0.014 g, 0.105 mmol) was added and the mixture was heated to 50 C for 12 h. After this time cesium carbonate (0.032 g, 0.105 mmol) was added and the mixture was heated to 50 C for 1 h. Further iodomethane (0.021 g, 0.152 mmol) and cesium carbonate (0.064 g, 0.201 mmol) were added and the mixture was heated to 50 C for 14 h. Sodium hydride (60% dispersion in mineral oil, 0.004 g, 0.105 mmol) and further iodomethane (0.042 g, 0.304 mmol) were added and the mixture stirred for 1 h at 50 C. The mixture was quenched with water/ammonia/MeOH (1 mL) and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and concentrated under vacuum. The solid was dissolved in DMF (0.5 mL) and Sodium hydride (60% dispersion in mineral oil, 0.006 g, 0.152 mmol) and iodomethane (0.042 g, 0.304 mmol) were added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water/ammonia/MeOH (1 mL) and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and concentrated under vacuum. The residue was purified by HPLC Method B to afford the title compound (0.004 g, 8%).

Provenance & Evidence