An Automated Process for a Sequential Heterocycle/Multicomponent Reaction: Multistep Continuous Flow Synthesis of 5-(Thiazol-2-yl)-34-Dihydropyrimidin-2(1H)-ones

摘要

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.