Water → {2-[7-(3-cyano-pyridin-2-yloxy)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester

HRID 8099

Reaktionsgleichung

Reaktionsgleichung von HRID 8099
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([OH:19])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:26]1[N:33]=[CH:32][CH:31]=[CH:30][C:27]=1[C:28]#[N:29].O>CN(C)C=O>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([O:19][C:26]3[C:27]([C:28]#[N:29])=[CH:30][CH:31]=[CH:32][N:33]=3)[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 810792-ChloronicotinonitrileHCID 69519112[2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 69516986{2-[7-(3-cyano-pyridin-2-yloxy)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl esterAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of [2-(7-Hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (274 mg, 0.900 mmol) in dimethylformamide (15 mL) is added sodium hydride (26 mg, 1.07 mmol). The mixture is stirred at ambient temperature for 25 minutes under nitrogen. 2-Chloro-nicotinonitrile (187 mg, 1.35 mmol) is added and the mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen. Water (50 ml) is added to quench the reaction and the mixture is extracted three times with 50 mL of ethyl acetate. The organic layers are combined and washed twice with 50 mL of 1.00 N sodium hydroxide. The organic layer is dried with sodium sulfate, filtered and the solvent evaporated. The residue is dissolved in dichloromethane and purified using silica gel chromatography (6% 2M ammonia in methanol, 94% dichloromethane used as mobile phase) to give 350 mg (96%) of {2-[7-(3-cyano-pyridin-2-yloxy)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester. FDMS m/e=407 (M++1).

Aufarbeitung

  1. temperaturethe mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture is extracted three times with 50 mL of ethyl acetate
  5. washwashed twice with 50 mL of 1.00 N sodium hydroxide
  6. dry with materialThe organic layer is dried with sodium sulfate
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. dissolutionThe residue is dissolved in dichloromethane
  10. custompurified

Quellen und Nachweise

ORD-Eintrag
ord-c661d089a084439e8ed863fc8eb54792
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07087635B2

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