Cesium carbonate → HCID 178479983, Verbindung

HRID 407693Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 407693
[NH2:1][C:2]1[N:6](C(OC(C)(C)C)=O)[N:5]=[C:4]([CH:14]2[CH2:16][CH2:15]2)[CH:3]=1.Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[CH:23]=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:24][C:22]1[CH:23]=[C:18]([NH:1][C:2]2[NH:6][N:5]=[C:4]([CH:14]3[CH2:15][CH2:16]3)[CH:3]=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 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 113565135-Amino-3-cyclopropyl-1H-pyrazole-1-carboxylic acid 1,1-dimethylethyl ester

Produkt 1

HCID 178479983HCID 178479983, VerbindungAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (15 mL), 126c (455 mg, 1.95 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (0.40 g, 1.5 mmol), and cesium carbonate (1.22 g, 3.75 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (87 mg, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium(0) (70 mg, 0.075 mmol) were added. The reaction mixture was refluxed for 15 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on silica-gel column eluting with 50:1 dichloromethane/methanol to afford 126d as a yellow solid (320 mg, 70%). MS: [M+H]+ 309. 1H NMR (500 MHz, DMSO-d6) δ 11.85 (s, 1H), 8.23 (s, 1H), 8.02 (d, J=2.5 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 5.77 (d, J=2.0 Hz, 1H), 3.46 (s, 3H), 1.84-1.82 (m, 1H), 0.92-0.90 (m, 2H), 0.65-0.64 (m, 2H).

Aufarbeitung

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  3. temperatureThe reaction mixture was refluxed for 15 h
  4. filtrationfiltered
  5. customThe filtrate was partitioned between ethyl acetate (30 mL) and water (30 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate (2×50 mL)
  8. washThe combined organic layer was washed with brine (50 mL)
  9. dry with materialdried over sodium sulfate
  10. customThe drying agent was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified on silica-gel column
  13. washeluting with 50:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-e4f96bee031141b5bfb0f31bfd8fa26f
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754077B2

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