Reaktion #307775

Reaktionsgleichung

3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl

potassium carbonate

tricyclohexylphosphine

racemic 2-(4-bromo-phenyl)-propionitrile

4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl]

potassium acetate

→

2-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-propionitrile

Ausbeute 107.8%

Lösungsmittel

water

N,N-dimethylacetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturCool
2. 2
   Sonstigereaction to room temperature
3. 3
   TemperaturCool to room temperature
4. 4
   Sonstigepurify by SCX-2® chromatography
5. 5
   Waschenwashing with methanol
6. 6
   Waschenthen eluting with 2 M ammonia in methanol
7. 7
   SonstigeFurther purify
8. 8
   Waschen(silica gel chromatography, eluting with 0:100 to 20:80 methanol:DCM)

Vorschrift

Stir together bis(dibenzylideneacetone)palladium(0) (35 mg, 0.06 mmol) and tricyclohexylphosphine (39 mg, 0.06 mmol) in N,N-dimethylacetamide (4 mL) at room temperature under nitrogen for 20 min. Add racemic 2-(4-bromo-phenyl)-propionitrile (420 mg, 2.00 mmol), then 4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl] (521 mg, 2.05 mmol) and potassium acetate (294 mg, 3.00 mmol) and stir at 80° C. for 16 hr. Cool reaction to room temperature, add 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (307 mg, 1.00 mmol), potassium carbonate (332 mg, 2.40 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0056 mmol) and water (2 mL), then stir at 120° C. for 8 hr. Cool to room temperature, purify by SCX-2® chromatography washing with methanol then eluting with 2 M ammonia in methanol. Further purify (silica gel chromatography, eluting with 0:100 to 20:80 methanol:DCM), to give the free base racemate 2-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-propionitrile as a powder (433 mg, 107%). MS (ES): m/z=402 [M+H]+.

Quelle