Реакция #85481

Уравнение реакции

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

Выход 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

Выход 83.3%

Растворители

dichloromethane

ethyl acetate

Условия реакции

Обработка

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

Методика

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.

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