Cesium carbonate → 5-Bromo-1-methyl-3-(6-(trifluoromethyl)pyridazin-3-ylamino)pyridin-2(1H)-one

HRID 1412038Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1412038
[F:1][C:2]([F:11])([F:10])[C:3]1[N:8]=[N:7][C:6]([NH2:9])=[CH:5][CH:4]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:55]1[C:56](=[O:63])[N:57]([CH3:62])[CH:58]=[C:59]([Br:61])[CH:60]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[Br:61][C:59]1[CH:60]=[C:55]([NH:9][C:6]2[N:7]=[N:8][C:3]([C:2]([F:1])([F:10])[F:11])=[CH:4][CH:5]=2)[C:56](=[O:63])[N:57]([CH3:62])[CH:58]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 598058596-(Trifluoromethyl)pyridazin-3-amine

Produkt 1

HCID 866845485-Bromo-1-methyl-3-(6-(trifluoromethyl)pyridazin-3-ylamino)pyridin-2(1H)-oneAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 301a (750 mg, 4.6 mmol), XantPhos (532 mg, 0.92 mmol), Pd2 dba3 (421 mg, 0.46 mmol), 2-bromo-4-chloronicotinaldehyde (H-001) (1.84 g, 6.9 mmol), Cs2CO3 (3.0 g, 9.2 mmol), and 1,4-dioxane (50 mL). The system was subjected to three cycles of vacuum/argon flush and heated at 90° C. for overnight. After the completion of the reaction, the mixture was filtered and the solid was washed with methanol (30 mL). The combined filtrate was evaporated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 301b (1.38 g, 89%) as a yellow solid. MS-ESI: [M+H]+ 350.8

Aufarbeitung

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. customAfter the completion of the reaction
  4. filtrationthe mixture was filtered
  5. washthe solid was washed with methanol (30 mL)
  6. customThe combined filtrate was evaporated under reduced pressure
  7. customthe residue was purified by silica-gel column chromatography
  8. washeluting with 20:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-891f76d10ac043708424dd4991256f66
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921353B2

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