Реакция #307747

Уравнение реакции

water

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

potassium carbonate

water

4-acetylbenzene boronic acid

→

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

Выход 97.0%

Растворители

N,N-dimethylacetamide

Условия реакции

Обработка

1. 1
   Температура, then cool to room temperature
2. 2
   Экстракцияextract with DCM (3×20 mL)
3. 3
   КонцентрированиеConcentrate the filtrate
4. 4
   Другоеpurify by SCX-2® chromatography
5. 5
   Промывкаwashing with methanol
6. 6
   Промывкаthen eluting with 3.5 M ammonia in methanol
7. 7
   ДругоеFurther purify
8. 8
   Промывка(silica gel chromatography, eluting with 5:95 to 20:80 methanol:DCM)

Методика

Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (921 mg, 3.0 mmol) in N,N-dimethylacetamide (6 mL). Add potassium carbonate (996 mg, 7.2 mmol), 4-acetylbenzene boronic acid (590 mg, 3.6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0174 g, 0.015 mmol), then water (3 mL). Heat at 120° C. for 17 hr., then cool to room temperature, add water (15 mL) and extract with DCM (3×20 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®. Concentrate the filtrate and purify by SCX-2® chromatography washing with methanol then eluting with 3.5 M ammonia in methanol. Further purify (silica gel chromatography, eluting with 5:95 to 20:80 methanol:DCM), to give 1-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-ethanone as a yellow powder (1.135 g, 97%). MS (ES): m/z=391 [M+H]+.

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