Reaktion #307769

Reaktionsgleichung

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

potassium carbonate

2-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionitrile

water

→

title compound

Ausbeute 35.0%

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

Ausbeute 35.0%

Lösungsmittel

N,N-dimethylacetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige, then purify by SCX-2® chromatography
2. 2
   Waschenwashing with methanol
3. 3
   WaschenElute with 2 M ammonia in methanol
4. 4
   Einengenconcentrate
5. 5
   SonstigePurify by low pH reverse phase HPLC
6. 6
   Sonstigeform the free base
7. 7
   Waschenwashing with methanol
8. 8
   Waschenthen eluting with 2 M ammonia in methanol
9. 9
   Einengenconcentrate
10. 10
    workup.DISSOLUTIONDissolve the free base in acetonitrile
11. 11
    workup.ADDITIONby adding 2 M aq HCl solution

Vorschrift

Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (307 mg, 1.0 mmol) in N,N-dimethylacetamide (4 mL). Add potassium carbonate (332 mg, 2.4 mmol), 2-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionitrile (300 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0058 mmol), then water (2 mL) and degas with nitrogen for 10 min. Heat at 120° C. for 20 hr., then purify by SCX-2® chromatography washing with methanol. Elute with 2 M ammonia in methanol and concentrate. Purify by low pH reverse phase HPLC, then form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 2 M ammonia in methanol and concentrate. Dissolve the free base in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a light yellow powder (158 mg, 35%). MS (ES): m/z=416 [M+H]+.

Quelle