Cesium carbonate → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-5-[(1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 593060

Reaktionsgleichung

Reaktionsgleichung von HRID 593060
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:32][CH2:31][N:30]3[C:23](=[CH:24][C:25]4[CH2:26][C:27]([CH3:34])([CH3:33])[CH2:28][C:29]=43)[C:22]2=[O:35])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2].[O:36]1[CH:40]=[CH:39][C:38]([NH2:41])=[N:37]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>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:32][CH2:31][N:30]3[C:23](=[CH:24][C:25]4[CH2:26][C:27]([CH3:34])([CH3:33])[CH2:28][C:29]=43)[C:22]2=[O:35])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:41][C:38]2[CH:39]=[CH:40][O:36][N:37]=2)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18102163-IsoxazolamineHCID 86684396[4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl Acetate

Produkt 1

HCID 86684522(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-5-[(1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with [4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricy-clo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate 273a (161 g, 0.30 mmol), isoxazol-3-amine (25 mg, 0.30 mmol), cesium carbonate (196 mg, 0.60 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, tris(dibenzylideneacetone)dipalladium(0) (14.0 mg, 0.015 mmol) and xantphos (17 mg, 0.030 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 (2×10 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 286a (96 mg, 59%) as yellow solid. MS-ESI: [M+H]+ 542.8.

Aufarbeitung

  1. customA 25-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 (2×10 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-1ebf85a24baa4987b5d73806b0aba440
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238655B2

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