反应详情

To a mixture of 1-acetyl-3-{5-chloro-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}imidazolidin-2-one (228 mg) described in Preparation Example 234, pyrrolidin-2-one (64 mg), tripotassium phosphate (149 mg), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (52 mg) and 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (24 mg) was added tert-butanol (1.5 mL), and the mixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated and methanol (1.6 mL), 1N aqueous sodium hydroxide solution (0.75 mL) were added to the obtained crude product of 1-acetyl-3-[2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(2-oxopyrrolidin-1-yl)phenyl}imidazolidin-2-one, 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 (69 mg).

1. temperaturewith heating
2. temperatureunder reflux for 8 hr
3. temperatureThe reaction mixture was cooled
4. extractionthe mixture was extracted with ethyl acetate
5. customThe solvent was evaporated
6. additionmethanol (1.6 mL), 1N aqueous sodium hydroxide solution (0.75 mL) were added to the