Water → N-(4-((6-Ethoxy-1H-indol-5-yl)oxy)pyridin-2-yl)acetamide

HRID 1427014

Reaktionsgleichung

Reaktionsgleichung von HRID 1427014
[CH2:1]([O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[OH:13])[CH3:2].Cl[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:16]=1.CC(C)([O-])C.[K+].O>CS(C)=O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[O:13][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:16]=1)[CH3:2]

Komponenten

7

Edukt 4

HCID 962WaterHCID 22832129N-(4-Chloropyridin-2-yl)acetamideHCID 23665647Potassium tert-butoxideHCID 846558946-Ethoxy-1H-indol-5-ol

Produkt 1

HCID 86730318N-(4-((6-Ethoxy-1H-indol-5-yl)oxy)pyridin-2-yl)acetamideAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

6-Ethoxy-1H-indol-5-ol described in Production Example 15-4 (7.0 g, 39.5 mmol) was dissolved in dimethylsulfoxide (40 mL) under nitrogen atmosphere, then N-(4-chloropyridin-2-yl)acetamide described in Production Example 1-5 (8.09 g, 47.4 mmol) and potassium tert-butoxide (4.88 g, 43.5 mmol) were added at room temperature, and the mixture was heated and stirred at 160° C. for 4 hours. The reaction liquid was cooled to room temperature and water and ethyl acetate were added for partition. The aqueous layer was extracted with ethyl acetate and the combined organic layer was washed with water twice and then with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under vacuum. The residue was dissolved in dichloromethane, and the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=3:1-2:1-3:2-1:3-1:4-0:1), and then the target fraction was concentrated under vacuum to obtain the title compound (7.16 g, 58%).

Aufarbeitung

  1. additionwere added at room temperature
  2. temperaturethe mixture was heated
  3. customThe reaction liquid
  4. temperaturewas cooled to room temperature
  5. customfor partition
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washthe combined organic layer was washed with water twice
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under vacuum
  11. dissolutionThe residue was dissolved in dichloromethane
  12. customthe resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=3:1-2:1-3:2-1:3-1:4-0:1)
  13. concentrationthe target fraction was concentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3aa9a66dd4384c92abb7671f370c1fa1
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933099B2

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