반응 #85481

반응 방정식

BOP

diisopropylethylamine

1-(1-methylpiperidin-4-yl)piperazine

[5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid

NaOH

→

title compound

수율 83.3%

5-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-one

수율 83.3%

용매

dichloromethane

ethyl acetate

반응 조건

후처리

1. 1
   workup.STIRRINGwas stirred at room temperature for 15 minutes
2. 2
   기타The phases were separated
3. 3
   추출the aqueous phase was extracted with ethyl acetate (1×)
4. 4
   세척The combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×)
5. 5
   건조dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   기타the solvent was evaporated in vacuo
8. 8
   기타The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane)

실험 절차

200 mg (0.45 mmol) of BOP, 1.07 ml (6.17 mmol) of diisopropylethylamine and then 79 mg (0.43 mmol) of 1-(1-methylpiperidin-4-yl)piperazine were added to a solution of 150 mg (0.41 mmol) of [5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. 6 ml of a 2-molar NaOH were added to the reaction solution, and it was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate (1×). The combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane). 181 mg of the title compound were obtained as a white solid.

출처