Combinatorial solution-phase synthesis of alkyl (1S*,2S*,3R*,5R*,6R*)-1-alkyl-3-aryl-6-benzoylamino-1-hydroxy-7- oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-2-carboxylates

J Comb Chem. 2007 Jul-Aug;9(4):717-23. doi: 10.1021/cc070041s. Epub 2007 Jun 13.

Abstract

Combinatorial solution-phase cycloadditions of (1Z,4R*,5R*)-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines 3 to beta-keto esters 4 afforded a library of 26 bicyclic pyrazolidinones 5 in 6-89% yields and in 14-100% de. All products were isolated in >90% purity according to 1H NMR, and 25 of them were analytically pure. The structures of cycloadducts were confirmed by NMR and X-ray diffraction. Most of the products were isolated as mixtures of the major (1S*,2S*,3R*,5R*,6R*)-epimers 5 and the minor (1R*,2S*,3R*,5R*,6R*)-epimers 6. Epimerization of cycloadducts 5/6 at the anomeric position 1 in solution was confirmed by 1H NMR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amines / chemistry*
  • Azo Compounds / chemistry
  • Benzene / chemistry*
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry*
  • Esters / chemistry
  • Hydroxylation
  • Imines / chemistry
  • Molecular Structure
  • Oxygen / chemistry*
  • Pyrazoles / chemistry*
  • Solutions
  • Thiosemicarbazones / chemistry

Substances

  • Amines
  • Azo Compounds
  • Carboxylic Acids
  • Esters
  • Imines
  • Pyrazoles
  • Solutions
  • Thiosemicarbazones
  • azomethine
  • pyrazole
  • Benzene
  • Oxygen