Cesium carbonate → 4-Chloro-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde

HRID 1022028Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1022028
[C:1]1(=[O:13])[C:5]2[CH:6]=[C:7]3[N:12]([C:4]=2[CH2:3][NH:2]1)[CH2:11][CH2:10][CH2:9][CH2:8]3.Br[C:15]1[N:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:16]=1[CH:17]=[O:18].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.C([O-])([O-])=O.[Cs+].[Cs+]>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>[Cl:23][C:19]1[C:16]([CH:17]=[O:18])=[C:15]([N:2]2[CH2:3][C:4]3[N:12]4[C:7]([CH2:8][CH2:9][CH2:10][CH2:11]4)=[CH:6][C:5]=3[C:1]2=[O:13])[N:22]=[CH:21][CH:20]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866839142-Bromo-4-chloropyridine-3-carbaldehydeHCID 866844512,3,5,6,7,8-Hexahydro-1H-pyrrolo[3,4-b]indolizin-1-one

Produkt 1

HCID 866844524-Chloro-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehydeAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 238d (400 mg, 2.27 mmol), 2-bromo-4-chloronicotinaldehyde (1.50 g, 6.90 mmol, 3.0 eq.), Pd2(dba)3 (208 mg, 0.227 mmol, 0.1 eq.), xantphos (131 mg, 0.227 mmol, 0.1 eq.), Cs2CO3 (1.50 g, 4.54 mmol, 2.0 eq.), and dioxane (30 mL). After bubbling nitrogen through the resulting mixture for 30 minutes, the reaction mixture was stirred at 90° C. for 16 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residual was purified by silica-gel column chromatography eluting with 1:3 ethyl acetate/petroleum ether to afford 238e (300 mg, 42%) as a light yellow solid. MS-ESI: [M+H]+ 316.1.

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 mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residual was purified by silica-gel column chromatography
  7. washeluting with 1:3 ethyl acetate/petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-01cde6e342fc49ef92b5e150b38fd652
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716274B2

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