反应详情

(2S,4R)-2-Amino-4-ethoxy-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide hydrochloride (125 mg, 0.33 mmol) was dissolved in methanol (5 mL) and N,N-diisopropylethylamine (0.25 mL) was added. The solution was evaporated and the residue was dried. The resulting material was dissolved in acetonitrile (6 mL) containing N,N-diisopropylethylamine (0.25 mL). To this solution was added (E)-4-bromo-3-(2,3-dichloro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 77, 143 mg, 0.40 mmol). The mixture was refluxed for 7 h. Solvents were evaporated and the residue was extracted with ethyl acetate and water. The organic layer was dried and concentrated. The crude product was purified by flash column chromatography (silica gel, 20-100% ethyl acetate/hexanes) to afford 3-(2,3-dichloro-phenoxy)-4-{(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butylamino}-but-2-enoic acid ethyl ester (60 mg). LR-ES-MS m/z calculated for C26H36Cl2N4O6 [M]+ 570, observed [M+H]+ 571.

1. customThe solution was evaporated
2. customthe residue was dried
3. dissolutionThe resulting material was dissolved in acetonitrile (6 mL)
4. additioncontaining N,N-diisopropylethylamine (0.25 mL)
5. temperatureThe mixture was refluxed for 7 h
6. customSolvents were evaporated
7. extractionthe residue was extracted with ethyl acetate and water
8. customThe organic layer was dried
9. concentrationconcentrated
10. customThe crude product was purified by flash column chromatography (silica gel, 20-100% ethyl acetate/hexanes)