Potassium Phosphate, Tribasic → 1-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine

HRID 1984429

Reaktionsgleichung

Reaktionsgleichung von HRID 1984429
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:21]1[C:22]([C:32]#[N:33])=[N:23][N:24]([CH3:31])[C:25]=1[CH2:26][CH2:27][CH2:28][CH2:29][Cl:30]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[Cl:30][CH2:29][CH2:28][CH2:27][CH2:26][C:25]1[N:24]([CH3:31])[N:23]=[C:22]2[C:21]=1[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[N:2]=[C:32]2[NH2:33]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 164270902-Aminophenylboronic acid hydrochlorideHCID 669589924-bromo-5-(4-chlorobutyl)-1-methyl-1H-pyrazole-3-carbonitrile

Produkt 1

HCID 577175021-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amineAusbeute 13,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

2-Aminophenylboronic acid hydrochloride (9.20 g, 53.0 mmol), potassium phosphate (28.0 g, 133 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (685 mg, 0.662 mmol), and bis[(2-diphenylphosphino)phenyl]ether (428 mg, 0.795 mmol) were added to a mixture of 4-bromo-5-(4-chlorobutyl)-1-methyl-1H-pyrazole-3-carbonitrile (7.30 g, 26.5 mmol) and powdered molecular sieves (1 g) in toluene (165 mL). Nitrogen was bubbled through the reaction mixture, and then the reaction was heated at 110° C. for 24 hours. The mixture was filtered through a layer of silica gel (eluting with 3:2 chloroform/methanol). The filtrate was concentrated under reduced pressure and dissolved in ethanol (130 mL). Hydrogen chloride (20 mL of a 4 M solution in ethanol) was added to the solution and the reaction was heated at reflux for two hours and allowed to cool to ambient temperature. The reaction was worked up as described in Part F of Example 19. After purification by chromatography on a HORIZON HPFC system, the solid was stirred in acetonitrile and filtered to provide 1.0 g of 1-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine that was used in the next step. The filtrate was concentrated to provide an additional 4.0 g of product.

Aufarbeitung

  1. customNitrogen was bubbled through the reaction mixture
  2. filtrationThe mixture was filtered through a layer of silica gel (eluting with 3:2 chloroform/methanol)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutiondissolved in ethanol (130 mL)
  5. additionHydrogen chloride (20 mL of a 4 M solution in ethanol) was added to the solution
  6. temperaturethe reaction was heated
  7. temperatureat reflux for two hours
  8. temperatureto cool to ambient temperature
  9. customAfter purification by chromatography on a HORIZON HPFC system
  10. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-b332ecaadee1476fa416cd92f9344e31
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544697B2

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