反应详情

温度

90 °C

To a solution of 5-(trifluoromethyl)pyrazin-2-amine (146 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol), cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine (77.7 mg, 0.13 mmol) in dioxane (10.0 ml) was added tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) and the reaction mixture purged with argon (3×) before being warmed to 90° C. for 18 hr. The mixture was cooled, diluted with dichloromethane and water (50 mL) and the layers separated. The aqueous phase was extracted with methylene chloride (2×25 mL). The organic phases were combined and dried over MgSO4. The mixture was filtered and evaporated and the residue purified via automated flash chromatography (Analogix, SF15-24 g column, 1%-10% methanol/dichloromethane gradient) to give 6-chloro-2-methyl-4-(5-trifluoromethyl-pyrazin-2-ylamino)-2H-pyridazin-3-one (197 mg, 72%) as a yellow solid: LC/MS m/e calculated for C10H7ClF3N5O [M]+305.03, observed 305.9

1. customthe reaction mixture purged with argon (3×)
2. temperatureThe mixture was cooled
3. additiondiluted with dichloromethane and water (50 mL)
4. customthe layers separated
5. extractionThe aqueous phase was extracted with methylene chloride (2×25 mL)
6. dry with materialdried over MgSO4
7. filtrationThe mixture was filtered
8. customevaporated
9. customthe residue purified