Rapid scaffold decoration of priveliged dihydropyrimidine cores using microwave-assisted synthesis

ORGN 47

C. Oliver Kappe, Doris Dallinger, Alenka Lengar, Bogdan Khanetskiy, and Bimbisar Desai. Institute of Chemistry, Karl-Franzens-University of Graz, Heinrichstrasse 28, Graz, A-8010, Austria
The exploration of privileged structures in drug discovery is a rapidly emerging theme in medicinal chemistry. In the last decade a considerable amount of attention has focused on multicomponent condensation reactions (MCRs) of the Biginelli type. The heterocyclic pyrimidine derivatives (DHPMs) derived from the acid-catalyzed condensation of a ß-ketoester, aldehyde and (thio)urea building block represents a “privileged scaffold” with remarkable pharmacological properties. We have previously reported the generation of libraries of DHPMs, employing an automated, sequential microwave-assisted solution phase strategy. This presenation describes high-speed microwave scaffold decorations around the DHPM heterocyclic core exploiting the diversity on at least six positions around the scaffold. This opens up the preparations of a very large number of highly diverse analogs given the commercial availability of the building blocks that are used in the functionalization process. The use of resin- and fluorous-bound catalysts, reagents, and scavengers in conjunction with microwave heating will be discussed.
 

Microwave-Assisted Organic Synthesis
1:00 PM-5:05 PM, Sunday, August 22, 2004 Pennsylvania Convention Center -- Ballroom A, Oral

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004