Cesium carbonate → ethyl (2E)-3-(5-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-2-pyrazinyl)acrylate

Temperatur

95 °C

Ethyl (2E)-3-(5-chloro-2-pyrazinyl)acrylate (4.70 g) and (3R)-1-(cyclohexylmethyl)-3-piperidinamine (4.77 g) were combined in 1,4-dioxane (80 mL) at ambient temperature. To this solution were added palladium(II) acetate (248 mg) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl(652 mg) at the same temperature and the mixture was stirred for 5 minutes. To the resulting mixture was added cesium carbonate (10.1 g) and the mixture was heated at 95° C. for twenty-four hours. The reaction mixture was allowed to cool to ambient temperature and the insoluble solid was filtered off. The filtrate was concentrated in vacuo and the residue was extracted with chloroform (300 mL). The chloroform phase was washed with saturated sodium bicarbonate (100 mL) and brine (100 mL). The aqueous layer was reextracted with chloroform (100 mL). The organic phase were combined, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by a flash column chromatography eluting with a gradient solvent system from EtOAc-Hexane (1:1 v/v) to EtOAc to afford ethyl (2E)-3-(5-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-2-pyrazinyl)acrylate (4.80 g) as a yellow amorphous solid.

1. temperatureto cool to ambient temperature
2. filtrationthe insoluble solid was filtered off
3. concentrationThe filtrate was concentrated in vacuo
4. extractionthe residue was extracted with chloroform (300 mL)
5. washThe chloroform phase was washed with saturated sodium bicarbonate (100 mL) and brine (100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by a flash column chromatography
9. washeluting with a gradient solvent system from EtOAc-Hexane (1:1 v/v) to EtOAc

ORD-Eintrag

ord-a2c7edfd14b046e793d282a64018ef03

Quelldatensatz

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07465731B2