反应详情

To a solution of 800 mg of [5-chloro-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid, which is the compound described in Preparation 1.1 of the brochure WO03/008407 and 488 mg of HOBt/H2O in DMF (8 ml) was added 554 mg of EDC/HCl under ice cooling, then, the reaction mixture was warmed to room temperature and stirred at room temperature for 30 minutes. The solution was cooled with ice again, 433 mg of 2-piperazin-1-yl pyrimidine was added to the reaction solution, and after warming to room temperature, the reaction mixture was stirred at room temperature for 14 hours. To the reaction solution was added EtOAc, a saturated aqueous solution of K2CO3 and water, and the mixture was stirred for 30 minutes. Liquid separation was performed, the obtained aqueous layer was extracted with EtOAc, the combined organic layer was washed with water and saturated brine, then, was dried over MgSO4, the drying agent was separated by filtration, then the solvent was evaporated under reduced pressure. The obtained residue was subjected to column chromatography (silicagel 60; mobile phase: CHCl3/MeOH/OH=10/1/0.1; v/v/v) to obtain 1.09 g of the title compound (colorless solid).

1. temperatureThe solution was cooled with ice again
2. temperatureafter warming to room temperature
3. stirringthe reaction mixture was stirred at room temperature for 14 hours
4. customLiquid separation
5. extractionthe obtained aqueous layer was extracted with EtOAc
6. washthe combined organic layer was washed with water and saturated brine
7. dry with materialwas dried over MgSO4
8. customthe drying agent was separated by filtration
9. customthe solvent was evaporated under reduced pressure