反应详情

(2S,4S)-2-Amino-4-ethoxy-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide hydrochloride (150 mg, 0.40 mmol) was dissolved in methanol (5 mL) and N,N-diisopropylethylamine (0.3 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 (0.3 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, 286 mg, 0.80 mmol). The mixture was refluxed for 7 h. The solvents were evaporated and the residue was treated with ethyl acetate and water. The layers were separated and the organic layer was dried and concentrated. The crude product was purified by flash column chromatography (silica gel, 20-100% ethyl acetate/hexanes) to give 3-(2,3-dichloro-phenoxy)-4-{(1S,3S)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butylamino}-but-2-enoic acid ethyl ester (120 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 (0.3 mL)
5. temperatureThe mixture was refluxed for 7 h
6. customThe solvents were evaporated
7. additionthe residue was treated with ethyl acetate and water
8. customThe layers were separated
9. customthe organic layer was dried
10. concentrationconcentrated
11. customThe crude product was purified by flash column chromatography (silica gel, 20-100% ethyl acetate/hexanes)