反应详情

To a mixture of N-{5-bromo-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-N-methylmethanesulfonamide (540 mg) described in Preparation Example 227 and 1-acetylimidazolidin-2-one (144 mg), cesium carbonate (731 mg), copper(I) iodide (107 mg) were added dioxane (3 mL) and N,N′-dimethylethylenediamine (121 μL), and the mixture was stirred under refluxing for 8 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated, methanol (2 mL) and 1N aqueous sodium hydroxide solution (1.7 mL) were added to the obtained residue, and the mixture was stirred at 40° C. for 3 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography (ethyl acetate:methanol) to give the title compound (330 mg).

1. temperatureunder refluxing for 8 hr
2. temperatureAfter cooling
3. extractionthe mixture was extracted with ethyl acetate
4. customThe solvent was evaporated
5. additionmethanol (2 mL) and 1N aqueous sodium hydroxide solution (1.7 mL) were added to the obtained residue
6. stirringthe mixture was stirred at 40° C. for 3 hr
7. temperatureAfter cooling
8. additionwater was added to the reaction mixture
9. extractionthe mixture was extracted with ethyl acetate
10. customThe solvent was evaporated
11. customthe residue was purified by column chromatography (ethyl acetate:methanol)