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An Automated Process for a Sequential Heterocycle/Multicomponent Reaction: Multistep Continuous Flow Synthesis of 5-(Thiazol-2-yl)-3,4-Dihydropyrimidin-2(1H)-ones

Abstract

The first example of a sequential heterocycle formation/multicomponent reaction using an automated continuous flow microreactor assembly is reported. Consecutive Hantzsch thiazole synthesis, deketalization, and Biginelli multicomponent reaction provides rapid and efficient access to highly functionalized, pharmacologically significant 5-(thiazol-2-yl)-3,4-dihydropyrimidin-2(1H)-ones without isolation of intermediates. These complex small molecules are generated in reaction times less than 15 min and in high yields (39–46%) over three continuous chemical steps.

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Correspondence to Nicholas D. P. Cosford.

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Pagano, N., Herath, A. & Cosford, N.D.P. An Automated Process for a Sequential Heterocycle/Multicomponent Reaction: Multistep Continuous Flow Synthesis of 5-(Thiazol-2-yl)-3,4-Dihydropyrimidin-2(1H)-ones. J Flow Chem 1, 28–31 (2011). https://doi.org/10.1556/jfchem.2011.00001

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Keywords

  • flow chemistry
  • microreactors
  • multistep synthesis
  • Hantzsch thiazole synthesis
  • hydrobromic acid
  • Biginelli reaction