Traceless Solid Phase Synthesis of Bicyclic Dihydropyrimidone Libraries Using Microwave-Assisted Cyclization Cleavage

Rolando Pérez, Doris Dallinger and C. Oliver Kappe, Karl-Franzens University

Date Posted: Tuesday, July 25, 2006

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4-Aryl-3,4-dihydro-2(1H)-pyrimidone esters ("Biginelli compounds", DHPMs) represent a heterocyclic system of remarkable pharmacological efficiency. More recently, appropriately functionalized DHPMs have emerged as potent calcium channel blockers, antihypertensive agents, a1a -adrenergic antagonists, mitotic kinesin Eg5 inhibitors and neuropeptide Y (NPY) antagonists. In recent years several different pathways for the synthesis of DHPMs have been reported, including combinatorial approaches, using e.g. solid phase reaction conditions. We now report a variation of the Biginelli condensation using methyl 4-chloroacetoacetate as the building block both in solution and in solid phase. This modification allows the rapid entry into a variety of bicyclic heterocyclic ring scaffolds.

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