Methane → 3-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

HRID 1890958Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1890958
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[CH:7][CH:6]=2.C(N(C(C)C)CC)(C)C.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.[CH3:71][C:72]1[CH:73]=[CH:74][C:75]2[N:76]([C:78]([SH:81])=[N:79][N:80]=2)[N:77]=1.C>CN(C=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]>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:81][C:78]1[N:76]3[N:77]=[C:72]([CH3:71])[CH:73]=[CH:74][C:75]3=[N:80][N:79]=1)=[CH:7][CH:6]=2

Komponenten

8

Edukt 5

HCID 297MethaneHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57911035Trifluoromethanesulfonic acid 3-bromo-quinolin-6-yl esterHCID 178423528HCID 178423528, Verbindung

Produkt 1

HCID 249009763-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinolineAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of trifluoromethanesulfonic acid 3-bromo-quinolin-6-yl ester (973 mg, 2.74 mmol), diisopropylethylamine (0.87 mL, 4.98 mmol) in DMF (9 mL) under nitrogen was degassed by bubbling in nitrogen for 20 min. Tris(dibenzylideneacetone)dipalladium (114 mg, 0.124 mmol, Strem catalyst) and Xantphos (144 mg, 0.249 mmol) were added together in one portion, followed by 6-methyl-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (450 mg, 2.49 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and 500 mg of activated decolorizing charcoal were added. The suspension was stirred for 2.5 h, and the mixture was directly filtered through a plug of silica gel, using DMF as eluent. The solvent was evaporated in vacuo, and the residue was partitioned between water and 10% methanol/dichloromethane. The organic layer was separated and adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-5% methanol/dichloromethane afforded 534 mg of 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline as a cream-colored solid (58% yield).

Aufarbeitung

  1. customby bubbling in nitrogen for 20 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringThe suspension was stirred for 2.5 h
  4. filtrationthe mixture was directly filtered through a plug of silica gel
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was partitioned between water and 10% methanol/dichloromethane
  7. customThe organic layer was separated
  8. customPurification by flash chromatography on silica gel using a gradient of 0-5% methanol/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-e30a46394e134fbeb3c9194bc93eae95
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08507489B2

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