Cesium carbonate → 5-Bromo-3-(5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 407733Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 407733
[F:1][CH:2]([F:14])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH2:13])[CH:12]=[C:6]2[CH2:5]1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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:22][C:20]1[CH:21]=[C:16]([NH:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([CH2:3][CH:2]([F:1])[F:14])[CH2:9][CH2:8][N:7]3[N:10]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=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 866840035-(2,2-Difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

Produkt 1

HCID 866840045-Bromo-3-(5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-oneAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 135b (290 mg, 1.43 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (383 mg, 1.43 mmol), cesium carbonate (932 mg, 2.86 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (82 mg, 0.143 mmol) and Pd2(dba)3 (65 mg, 0.072 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (30 mL). The combined organic filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 135c (400 mg, 72%) as a yellow solid. MS-ESI: [M+H]+ 387.8

Aufarbeitung

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (30 mL)
  8. concentrationThe combined organic filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel column chromatography
  10. washeluting with dichloromethane/methanol (80/1 to 30/1)

Quellen und Nachweise

ORD-Eintrag
ord-1d0b798096a349948f79733dbd410859
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754077B2

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