Cesium carbonate → 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1431118

Reaktionsgleichung

Reaktionsgleichung von HRID 1431118
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH2:8])=[N:3]1.Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[N:13]=[C:14]([Cl:16])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:16][C:14]1[CH:15]=[C:10]([NH:8][C:4]2[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=2)[C:11](=[O:18])[N:12]([CH3:17])[N:13]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70177471,5-dimethyl-1H-pyrazol-3-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Produkt 1

HCID 585400026-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-oneAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

1,5-Dimethyl-1H-pyrazol-3-amine (400 mg, 3.6 mmol, Eq: 1.00) and 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (965 mg, 4.32 mmol, Eq: 1.20) were combined with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (312 mg, 540 μmol, Eq: 0.15), cesium carbonate (3.52 g, 10.8 mmol, Eq: 3) and tris(dibenzylideneacetone)dipalladium(0) (165 mg, 180 μmol, Eq: 0.05) in dioxane (10.0 ml). The solution was degassed with Ar. The reaction mixture heated at 100° C. for 18 h. The mixture was cooled to room temperature. The solution was diluted with 100 ml DCM. The organic layer was washed with water. The organic layer was dried over MgSO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one (408 mg, 45%). LC/MS-ESI observed [M+H]+ 235.

Aufarbeitung

  1. customThe solution was degassed with Ar
  2. temperatureThe mixture was cooled to room temperature
  3. additionThe solution was diluted with 100 ml DCM
  4. washThe organic layer was washed with water
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 40 g, 10% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

Quellen und Nachweise

ORD-Eintrag
ord-0df8d9b61eb24f099e2575697cec672c
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940741B2

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