Potassium Phosphate, Tribasic → 4-(2-aminophenyl)-5-(4-chlorobutyl)-1-propyl-1H-pyrazole-3-carbonitrile

HRID 1984476

Reaktionsgleichung

Reaktionsgleichung von HRID 1984476
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:21]1[C:22]([C:34]#[N:35])=[N:23][N:24]([CH2:31][CH2:32][CH3:33])[C:25]=1[CH2:26][CH2:27][CH2:28][CH2:29][Cl:30]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:21]1[C:22]([C:34]#[N:35])=[N:23][N:24]([CH2:31][CH2:32][CH3:33])[C:25]=1[CH2:26][CH2:27][CH2:28][CH2:29][Cl:30]

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 164270902-Aminophenylboronic acid hydrochlorideHCID 669590374-bromo-5-(4-chlorobutyl)-1-propyl-1H-pyrazole-3-carbonitrile

Produkt 1

HCID 669588824-(2-aminophenyl)-5-(4-chlorobutyl)-1-propyl-1H-pyrazole-3-carbonitrileAusbeute 91,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

2-Aminophenyl boronic acid hydrochloride (9.10 mg, 26.3 mmol) and freshly ground potassium phosphate tribasic (27.8 g, 131 mmol) were added sequentially to a solution of 4-bromo-5-(4-chlorobutyl)-1-propyl-1H-pyrazole-3-carbonitrile (8.00 g, 26.3 mmol), prepared as described in Example 46, in 100 mL of toluene in a pressure tube. Nitrogen was bubbled through the resultant slurry for 15 minutes. Tris(dibenzylideneacetone)dipalladium(0) (1.36 g, 1.31 mmol), bis[(2-diphenylphosphino)phenyl]ether (851 mg, 1.58 mmol), and 4 angstrom molecular sieves were then added to the reaction mixture. The pressure tube was sealed and heated in a 110° C. oil bath. After 24 hours, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through CELITE filter aid. The filtrate was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The aqueous layer was extracted with additional ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated to a red oil. Purification via flash column chromatography on silica gel (eluting with 2:1 hexane:ethyl acetate) afforded 7.60 g of 4-(2-aminophenyl)-5-(4-chlorobutyl)-1-propyl-1H-pyrazole-3-carbonitrile as a red oil.

Aufarbeitung

  1. customprepared
  2. customNitrogen was bubbled through the resultant slurry for 15 minutes
  3. customThe pressure tube was sealed
  4. temperaturethe reaction mixture was cooled to ambient temperature
  5. filtrationfiltered through CELITE
  6. filtrationfilter aid
  7. additionThe filtrate was diluted with ethyl acetate
  8. washwashed with saturated aqueous sodium bicarbonate
  9. extractionThe aqueous layer was extracted with additional ethyl acetate
  10. washthe combined organic layers were washed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to a red oil
  14. customPurification via flash column chromatography on silica gel (eluting with 2:1 hexane:ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-b310d71139114b1587904daaee817067
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544697B2

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