反应详情

To a solution of 700 mg 4-{2-[(5-Carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperazine-1-carboxylic acid butyl ester in 10 ml DMF were added 317 mg pentafluorophenol and 330 mg EDC. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. (2S,4R)-4-Hydroxy-pyrrolidine-2-carboxylic acid cyclobutylamide hydrotrifluoroacetate (455 mg) was mixed with 0.55 ml N-ethylmorpholine and 5 ml DMF and this mixture added dropwise to the solution of the pentafluorophenolester. After 12 h the reaction mixture was diluted with DCM and washed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were immediately lyophilized to yield the pure product which was taken up in dichloromethane and washed once with aqueous NaHCO3. The residue obtained after evaporation of the solvent was lyophilized again to give the title compound. Yield: 454 mg MS (ES+): m/e=654.

1. additionthis mixture added dropwise to the solution of the pentafluorophenolester
2. washwashed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine
3. customThe crude product obtained
4. customafter evaporation of the solvent
5. customwas purified by preparative HPLC (
6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
7. additionThe fractions containing the product
8. customto yield the pure product which
9. washwashed once with aqueous NaHCO3
10. customThe residue obtained
11. customafter evaporation of the solvent