Solid-phase synthesis of 1,2,5-trisubstituted 4-imidazolidinones

J Comb Chem. 2002 May-Jun;4(3):209-13. doi: 10.1021/cc0100565.

Abstract

An efficient method for the preparation of 1,2,5-trisubstituted 4-imidazolidinones is presented. The synthetic approach is based on the formation of an N-[1-(benzotriazol-1-yl)alkyl] moiety on the amino group of a MBHA resin-bound amino acid. The nucleophilic substitution of the benzotriazole group with an amidic nitrogen results in the formation of a five-membered imidazolidinone ring. The reaction is nonstereospecific and produces diastereomers in ratios that vary depending on the substituents on the ring. A variety of N-alpha-alkylated amino acids were cyclized with aromatic, aliphatic, and heterocyclic aldehydes to determine optimal reaction conditions and to select building blocks for the future preparation of a large, diverse range of individual trisubstituted imidazolidinones as well as a mixture-based combinatorial library.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / chemical synthesis
  • Combinatorial Chemistry Techniques / methods*
  • Cyclization
  • Imidazoles / chemical synthesis*
  • Resins, Synthetic

Substances

  • Amino Acids
  • Imidazoles
  • Resins, Synthetic