Cesium carbonate → 5-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-one

HRID 592853Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592853
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][C:5]=12.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[N:23]=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>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:24][C:22]1[N:23]=[C:18]([NH:10][C:7]2[CH:8]=[CH:9][N:4]3[CH:3]=[CH:2][N:1]=[C:5]3[CH:6]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 45087541Imidazo[1,2-a]pyridin-7-amine

Produkt 1

HCID 866843315-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-oneAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with imidazo[1,2-a]pyridin-7-amine (665 mg, 5.0 mmol), Cs2CO3 (3.26 g, 10 mmol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (1.86 g, 7.0 mmol), Xantphos (289 mg, 0.50 mmol), Pd2(dba)3 (458 mg, 0.50 mmol), and 1,4-dioxane (30 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 100° C. under nitrogen atmosphere for 16 h. Analysis of the reaction mixture by LCMS showed little starting material remained. The reaction mixture was cooled to room temperature and filtered. The filtrate was diluted with dichloromethane (60 mL) and water (50 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 mL). The combined organic layers was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (60/1 to 30/1) to afford 201a (700 mg, 44%) as light yellow solid. MS-ESI: [M+H]+ 320

Aufarbeitung

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. additionThe filtrate was diluted with dichloromethane (60 mL) and water (50 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with dichloromethane (3×20 mL)
  8. dry with materialThe combined organic layers was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe dark residue was purified by silica-gel column chromatography
  12. washeluting with dichloromethane/methanol (60/1 to 30/1)

Quellen und Nachweise

ORD-Eintrag
ord-559052a5369747e5bb0c62f861897c3c
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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