反应详情

Stir together 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (920 mg, 3.00 mmol), 4-(hydroxy)benzene boronic acid (497 mg, 3.6 mmol), potassium carbonate (996 mg, 7.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.015 mmol) and water (6 mL) in N,N-dimethylacetamide (12 mL) at 120° C. for 5 hr. Cool to room temperature, add water (20 mL), extract with DCM (3×30 mL) and pass through an IST Phase Separator Frit®. Purify using SCX chromatography, eluting with 2.5 M ammonia in methanol and further purify using silica gel chromatography (eluting with 5:95 to 15:85 methanol:DCM). Concentrate and dry in a vacuum oven over night to give 4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenol as a light yellow powder (936 mg, 86%). MS (ES): m/z=365 [M+H].

1. extractionextract with DCM (3×30 mL)
2. customPurify
3. washeluting with 2.5 M ammonia in methanol
4. customfurther purify
5. washsilica gel chromatography (eluting with 5:95 to 15:85 methanol:DCM)
6. concentrationConcentrate
7. customdry in a vacuum oven over night