Reaktion #68968

Reaktionsgleichung

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene

ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate

3-Chloroisoquinoline

caesium carbonate

→

ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate

Ausbeute 25.0%

Lösungsmittel

ether

toluene

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas degassed under a stream of nitrogen gas
2. 2
   Sonstigethe mixture was degassed for a further 5 minutes
3. 3
   workup.WAITat 130° C. for 20 minutes in a microwave reactor
4. 4
   SonstigeThe reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate
5. 5
   ExtraktionThe aqueous phase was re-extracted with ethyl acetate
6. 6
   Waschenthe combined organic layers were washed with brine
7. 7
   Trocknendried (Na2SO4)
8. 8
   Einengenconcentrated to dryness
9. 9
   SonstigeThe residue was triturated with methanol

Vorschrift

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).

Quelle