反应详情

To a stirred mixture of N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (100 mg, 0.33 mmol) (prepared as described in Example 28), 4-bromo-1-methyl-1H-imidazole (63.8 mg, 0.396 mmol) in 1,4-dioxane (6 ml) was added potassium phosphate (350 mg, 1.65 mmol), copper (I) iodide (62.8 mg, 0.33 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.052 ml, 0.33 mmol) and the mixture was heated at reflux under argon for 1 h. The mixture was cooled to room temperature and partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organic extracts were separated, washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 0-20% methanol in dichloromethane, followed by mass-directed automated HPLC to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamide (15 mg, 12%). LC/MS [M+H]+=384, retention time=1.71 minutes.

1. temperaturethe mixture was heated
2. temperatureat reflux under argon for 1 h
3. custompartitioned between saturated sodium hydrogen carbonate solution and dichloromethane
4. customThe organic extracts were separated
5. washwashed with water and brine
6. customdried
7. customevaporated
8. customThe residue was purified by silica gel chromatography
9. washeluting with 0-20% methanol in dichloromethane