Sodium hydride → HCID 67087432, Verbindung

HRID 57204

Reaktionsgleichung

Reaktionsgleichung von HRID 57204
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[S:13](Cl)(=[O:15])=[O:14].[Cl:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][C:26]=1[F:27])[NH:23][C:22](=[O:28])[C:21]2([C:45]1[C:46]([O:51][CH2:52][CH3:53])=[N:47][CH:48]=[CH:49][CH:50]=1)[CH2:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([CH:38]2[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]2)[CH2:34][CH2:33]1)=[O:31].ClCCl.CO>CN(C)C=O.C(OCC)(=O)C.O>[Cl:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][C:26]=1[F:27])[N:23]([S:13]([C:6]1[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=1[O:4][CH3:3])(=[O:15])=[O:14])[C:22](=[O:28])[C:21]2([C:45]1[C:46]([O:51][CH2:52][CH3:53])=[N:47][CH:48]=[CH:49][CH:50]=1)[CH2:29][C:30]([N:32]1[CH2:33][CH2:34][N:35]([CH:38]2[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]2)[CH2:36][CH2:37]1)=[O:31]

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 27346262,4-Dimethoxybenzenesulfonyl chlorideHCID 21226129Dichloromethane methanolHCID 670875065-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

Produkt 1

HCID 67087432HCID 67087432, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-d395206a7be74ea08d53025217de591a
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434713B2

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