Reaktion #307772

Reaktionsgleichung

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

4-acetamidophenylboronic acid

potassium carbonate

→

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

Ausbeute 38.0%

Lösungsmittel

N,N-dimethylacetamide

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePurify by normal phase chromatography with 6% 7N ammonia-methanol/ethyl acetate

Vorschrift

Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl hydrochloride salt (0.5 g, 1.63 mmol) in N,N-dimethylacetamide (5 mL) and water (2 mL). Add 4-acetamidophenylboronic acid (1.2 eq., 0.35 g, 1.96 mmol). Add tetrakis(triphenylphosphine)palladium(0) (0.01 eq., 0.019 g, 0.016 mmol). Add potassium carbonate (3.6 eq., 0.54 g, 3.9 mmol). Heat at 90° C. for 10 hr. Purify by normal phase chromatography with 6% 7N ammonia-methanol/ethyl acetate to give N-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-acetamide (0.25 g, 38%). MS (ES): m/z=406.2[M+H]. Dissolve this free base (0.25 g, 0.6 mmol) in acetonitrile (1 mL) and water (4 mL). Add aq. 1 N HCl (1 eq., 0.60 mmol, 0.60 mL). Freeze the solution to −78° C. in a dry-ice/acetone bath. Place the solution in the lyophilize for 48 hr. to give the title compound salt (0.26 g, 99%). MS (ES): m/z=406.2[M+H].

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