Cesium carbonate → Ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate

HRID 40690Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 40690
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:44]1[N:45]=[CH:46][C:47]2[C:52]([CH:53]=1)=[CH:51][CH:50]=[CH:49][CH:48]=2.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:60][C:61]1[N:66]=[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])[C:64]([C:74]#[N:75])=[N:63][CH:62]=1>C1(C)C=CC=CC=1.CN(C=O)C.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].CCOCC>[C:74]([C:64]1[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])=[N:66][C:61]([NH:60][C:44]2[N:45]=[CH:46][C:47]3[C:52]([CH:53]=2)=[CH:51][CH:50]=[CH:49][CH:48]=3)=[CH:62][N:63]=1)#[N:75]

Komponenten

9

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6409683-ChloroisoquinolineHCID 59636444Ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate

Produkt 1

HCID 44204747Ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetateAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of tris(dibenzylideneacetone)dipalladium (0) (39 mg, 0.043 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (50 mg, 0.086 mmol) in toluene (1.5 mL) and DMF (1.5 mL) was degassed under a stream of nitrogen gas with stirring for 15 minutes. 3-Chloroisoquinoline (70 mg, 0.428 mmol), caesium carbonate (279 mg, 0.856 mmol) and ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate (105 mg, 0.471 mmol) were added and the mixture was degassed for a further 5 minutes. The mixture was then heated at 100° C. for 20 minutes, then at 130° C. for 20 minutes in a microwave reactor. The reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate. The aqueous phase was re-extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), passed sequentially through two PS-Thiol cartridges and concentrated to dryness. The residue was triturated with methanol and then ether affording ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate (37 mg, 0.107 mmol, 25%). LC-MS (2) Rt 2.89 min; m/z (ESI+) 350 (M+H).

Aufarbeitung

  1. customwas degassed under a stream of nitrogen gas
  2. customthe mixture was degassed for a further 5 minutes
  3. waitat 130° C. for 20 minutes in a microwave reactor
  4. customThe reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate
  5. extractionThe aqueous phase was re-extracted with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customThe residue was triturated with methanol

Quellen und Nachweise

ORD-Eintrag
ord-e1a47ca270f246b19bfce3d4d1e88faf
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530468B2

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