Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines: An example of cyclization-assisted cleavage

José L. Falcó, Josep L. Matallana, Jaume Barberena, Jordi Teixidó, José I. Borrell

Research output: Indexed journal article Articlepeer-review

6 Citations (Scopus)

Abstract

An efficient solid-phase synthesis of 2-substituted 4-aminopyrido[2,3-d]pyrimidines 12 by cyclization-assisted cleavage from resin is reported. The procedure starts by solid supporting an α,β-unsaturated acid 8 to the Wang resin 13 by using DCC and 4-DMAP in THF. The resulting α,β-unsaturated ester 14 is converted to the Michael adduct by treatment with malononitrile in NaOMe/THF. Such Michael addition constitutes the first example of a Michael reaction with malononitrile in solid-phase. Finally, the Michael adducts 15 are treated with an amidine system in MeOH to yield the corresponding pyridopyrimidines 12. Compounds 12 present three diversity centers R1, R2 and G. Having validated the chemistry on solid support, a 40-membered combinatorial library was obtained using this protocol.

Original languageEnglish
Pages (from-to)3-11
Number of pages9
JournalMolecular Diversity
Volume6
Issue number1
DOIs
Publication statusPublished - 2003

Keywords

  • Combinatorial library
  • Cyclization-assisted cleavage
  • Michael reaction
  • Pyrido[2,3-d]pyrimidines
  • Solid-phase synthesis

Fingerprint

Dive into the research topics of 'Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines: An example of cyclization-assisted cleavage'. Together they form a unique fingerprint.

Cite this