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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Complete details of our study will be published in due course.
It should be noted that no improvement in yield was observed with addition of 1 equiv water to the a-bromoketone stock solution. Thus, water was not incorporated into the two-chip sequences.
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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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DOI: https://doi.org/10.1556/jfchem.2011.00001