Water → 5-(2-aminophenyl)-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile

HRID 1920257

Reaktionsgleichung

Reaktionsgleichung von HRID 1920257
O.C(=O)([O-])[O-].[Na+].[Na+].[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O.Br[C:19]1[N:23]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:22]([CH2:28][CH2:29][CH2:30][CH3:31])=[N:21][C:20]=1[C:32]#[N:33]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)CC>[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:19]1[N:23]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:22]([CH2:28][CH2:29][CH2:30][CH3:31])=[N:21][C:20]=1[C:32]#[N:33]

Komponenten

8

Edukt 4

HCID 962WaterHCID 10340Sodium Carbonate2×HCID 2773216(2-Aminophenyl)boronic acid2×HCID 585001335-bromo-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile

Produkt 1

HCID 585001415-(2-aminophenyl)-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrileAusbeute 843,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11776TriphenylphosphineKatalysator2×HCID 167845palladium(II) acetateKatalysator3×HCID 10311-PropanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Palladium (II) acetate (5.0 mg, 0.022 mmol), triphenylphosphine (17 mg, 0.067 mmol), water (2.6 mL), n-propanol (13 mL), and aqueous sodium carbonate (4.4 mL of 2 M) were added to 2-aminophenylboronic acid (1.11 g, 8.13 mmol) and 5-bromo-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile (2.10 g, 1.00 mmol). The reaction was placed under a nitrogen atmosphere and heated at 100° C. for 15 hours. An analysis by liquid chromatography/mass spectrometry (LC/MS) indicated the presence of starting material, and additional palladium (II) acetate (5.0 mg in 1 mL toluene) and triphenylphosphine (17 mg) were added. The reaction was heated at 100° C. for an additional 23.5 hours, and an analysis by LC/MS indicated the presence of starting material. Additional palladium (II) acetate (5.0 mg in 1 mL toluene), 2-aminophenylboronic acid (0.500 g), and aqueous sodium carbonate (2.2 mL of 2 M) were added, and the reaction was heated at reflux for an additional four hours and allowed to cool to room temperature. The reaction mixture was filtered to remove solid, and the filtrate was partitioned between 2M aqueous sodium carbonate and dichloromethane. The aqueous layer was separated and extracted twice with dichloromethane. The combined organic fractions were dried over magnesium sulfate, treated with decolorizing carbon, filtered, and concentrated under reduced pressure to provide 2.5 g of 5-(2-aminophenyl)-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile as a brown solid. The solid was recrystallized from a mixture hexanes (30 mL) and tert-butyl methyl ether (20 mL) after hot filtration to provide 1.51 g of product. A portion (0.48 g) was recrystallized from a mixture of hexanes (6 mL) and tert-butyl methyl ether (6 mL) to provide 5-(2-aminophenyl)-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile as a white solid.

Aufarbeitung

  1. additionwere added
  2. temperatureThe reaction was heated at 100° C. for an additional 23.5 hours
  3. temperaturethe reaction was heated
  4. temperatureat reflux for an additional four hours
  5. temperatureto cool to room temperature
  6. filtrationThe reaction mixture was filtered
  7. customto remove solid
  8. customthe filtrate was partitioned between 2M aqueous sodium carbonate and dichloromethane
  9. customThe aqueous layer was separated
  10. extractionextracted twice with dichloromethane
  11. dry with materialThe combined organic fractions were dried over magnesium sulfate
  12. additiontreated with decolorizing carbon
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-43b0f37a4060421094bb1dd22989c971
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08168802B2

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