反应详情

Combine 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.290 g, 0.786 mmol), potassium carbonate (0.261 g, 1.89 mmol), 4-(hydroxymethyl)phenylboronic acid (0.143 g, 0.943 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) in N,N-dimethylacetamide (1.6 mL). Add water (790 μL), and reflux reaction for 18 hr. Add 4-(hydroxymethyl)phenylboronic acid (0.072 g, 0.471 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (0.009 g, 0.008 mmol) and heat to 110° C. for 3.5 hr. Add DCM and wash with water. Extract water layer three times with DCM. Dry combined organics (magnesium sulfate) and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 methanol:ethyl acetate), to give the free base of the title compound (198 mg, 57%). Dissolve the free base (0.195 g, 0.443 mmol) in acetonitrile (531 μL) and add aq. 1 N HCl solution (531 μL, 0.531 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (208 mg, 98%). MS (ES): m/z=441 [M+H]+.

1. customreaction for 18 hr
2. washAdd DCM and wash with water
3. customDry
4. custompurify (silica gel chromatography
5. washeluting with 50:50 to 100:0 ethyl acetate