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

HRID 1360430

Reaktionsgleichung

Reaktionsgleichung von HRID 1360430
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:33]#[N:34])=[N:23][N:24]([CH2:31][CH3:32])[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]([CH2:31][CH3:32])[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:33]2[NH2:34]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 164270902-Aminophenylboronic acid hydrochlorideHCID 669582654-bromo-5-(4-chlorobutyl)-1-ethyl-1H-pyrazole-3-carbonitrile

Produkt 1

HCID 577175141-(4-chlorobutyl)-2-ethyl-2H-pyrazolo[3,4-c]quinolin-4-amineAusbeute 8 %

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 (1.88 g, 10.8 mmol), potassium phosphate (6.9 g, 32 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (186 mg, 0.18 mmol), and bis[(2-diphenylphosphino)phenyl]ether (116 mg, 0.217 mmol) were added to a solution of 4-bromo-5-(4-chlorobutyl)-1-ethyl-1H-pyrazole-3-carbonitrile (2.1 g, 7.2 mmol) in toluene (45 mL). Nitrogen was bubbled through the reaction mixture, and then the reaction was heated at 110° C. for 48 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 (36 mL). Hydrogen chloride (5.4 mL of a 4 M solution in ethanol) was added to the resulting solution, and the reaction was heated at reflux for two hours and allowed to cool to ambient temperature. The solvent was removed under reduced pressure, and the residue was adjusted to pH 11 with the addition of 2 M aqueous sodium carbonate. The mixture was diluted with brine and extracted with chloroform. The combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge, eluting with chloroform/CMA in a gradient from 100:0 to 70:30). The resulting dark semi-solid was recrystallized from acetonitrile to provide 175 mg of 1-(4-chlorobutyl)-2-ethyl-2H-pyrazolo[3,4-c]quinolin-4-amine as a tan solid.

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 (36 mL)
  5. additionHydrogen chloride (5.4 mL of a 4 M solution in ethanol) was added to the resulting solution
  6. temperaturethe reaction was heated
  7. temperatureat reflux for two hours
  8. temperatureto cool to ambient temperature
  9. customThe solvent was removed under reduced pressure
  10. additionthe residue was adjusted to pH 11 with the addition of 2 M aqueous sodium carbonate
  11. additionThe mixture was diluted with brine
  12. extractionextracted with chloroform
  13. dry with materialThe combined extracts were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge
  17. washeluting with chloroform/CMA in a gradient from 100:0 to 70:30)
  18. customThe resulting dark semi-solid was recrystallized from acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-27b0eb925f37437ea26ff5c9f8fe8f83
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879849B2

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