Reaktion #85482

Reaktionsgleichung

dichloromethane methanol

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

sodium hydride

2,4-dimethoxyphenylsulfonyl chloride

→

title compound

(+)-5-Chloro-1-(2,4-dimethoxyphenylsulfonyl)-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

Lösungsmittel

dimethylformamide

ethyl acetate

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe two phases were then separated
2. 2
   Extraktionthe aqueous phase was extracted once more with ethyl acetate (1×)
3. 3
   WaschenThe combined organic phase was washed with water (1×) and saturated sodium chloride solution (1×)
4. 4
   Trocknendried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Sonstigethe solvent was evaporated in vacuo
7. 7
   SonstigeThe residue was purified by preparative HPLC (RP, eluents acetonitrile/water, 0.01% TFA)

Vorschrift

16.3 mg (0.41 mmol, 60% w/w) of sodium hydride and, after 10 minutes, 96 mg (0.41 mmol) of 2,4-dimethoxyphenylsulfonyl chloride were added to a solution, cooled to 0° C., of 180 mg (0.34 mmol) of 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 in 2 ml of dimethylformamide. The reaction mixture was allowed to warm to room temperature and was stirred for a further 50 minutes. The progress of the reaction was followed by thin-layer chromatography (silica gel, dichloromethane/methanol 15:5). Water and ethyl acetate were added to the reaction mixture. The two phases were then separated and the aqueous phase was extracted once more with ethyl acetate (1×). The combined organic phase was 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 preparative HPLC (RP, eluents acetonitrile/water, 0.01% TFA). 116 mg (0.16 mmol, 46%, 99% purity) of the title compound were obtained as a white solid.

Quelle