反应详情

Heck coupling: A solution of [1-(4-bromo-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 12.1.1, 500 mg, 1.5 mmol), 4-trifluoromethyl-phenylacetylene (0.24 ml, 1.5 mmol) and diisopropylethylamine (0.51 ml, 3 mmol) in 15 ml tetrahydrofurane was degassed, and CuI (28 mg, 0.15 mmol) and bis-(triphenylphosphin)-palladium dichloride (104 mg, 0.15 mmol) were added to the solution. The mixture was refluxed for 12 h, the solvent evaporated under reduced pressure, and the residue was purified by MPLC (silica gel, cyclohexane/ethyl acetate 98:2). Saponification: The ester intermediate (170 mg, 0.4 mmol) was dissolved in 1 ml dioxan, 1 ml water and aqueous NaOH solution (0.8 ml, 1 M) was added. After stirring for 1 h, aqueous HCl solution (0.84 ml, 1 M) was added. The mixture was extracted with ethyl acetate, the organic layer was dried with MgSO4 and evaporated under reduced pressure. The residue was purified by MPLC (silica gel, CH2Cl2/methanol 9:1) and preparative reversed phase HPLC (gradient of methanol in water+0.1 NH3).

1. temperatureThe mixture was refluxed for 12 h
2. customthe solvent evaporated under reduced pressure
3. customthe residue was purified by MPLC (silica gel, cyclohexane/ethyl acetate 98:2)
4. extractionThe mixture was extracted with ethyl acetate
5. dry with materialthe organic layer was dried with MgSO4
6. customevaporated under reduced pressure
7. customThe residue was purified by MPLC (silica gel, CH2Cl2/methanol 9:1) and preparative reversed phase HPLC (gradient of methanol in water+0.1 NH3)