Continuous-Flow retro-Diels–Alder Reaction: A Process Window for Designing Heterocyclic Scaffolds

Imane Nekkaa, Márta Palkó, István M. Mándity, Ferenc Miklós, Ferenc Fülöp

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The synthesis of racemic and enantiopure tricyclic and tetracyclic pyrrolopyrimidinones, pyrimidoisoindoles, and spiropyrimidinones, as valuable new chemical entities (NCE), based on a highly controlled continuous-flow (CF) retro-Diels–Alder protocol is presented. This approach ensures enhanced safety, and gave the target pyrimidinone derivatives 17–25 in yields higher than those obtained in batch and microwave processes. These results were achieved through careful optimization of the reaction parameters. We also developed an alternative time-efficient route for the synthesis of intermediate quinazolinones 2–16 involving a three-step domino ring-closure reaction followed by spirocyclization under continuous-flow conditions, starting from β-aminonorbornene carboxamides 1a–1d and γ-keto acids or cycloalkanones.

Original languageEnglish
Pages (from-to)4456-4464
Number of pages9
JournalEuropean Journal of Organic Chemistry
Volume2018
Issue number32
DOIs
Publication statusPublished - Aug 31 2018

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Keywords

  • Cycloaddition
  • Flow chemistry
  • Microreactors
  • Nitrogen heterocycles
  • Spiro compounds
  • Synthetic methods

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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