5-aroyl-3,4-dihydropyrimidin-2-one library generation via automated sequential and parallel microwave-assisted synthesis techniques.
An efficient two-step synthetic pathway toward the preparation of diversely substituted 5-aroyl-3,4-dihydropyrimidin-2-ones is realized. The protocol involves an initial trimethylsilyl chloride-mediated Biginelli multicomponent reaction involving S-ethyl acetothioacetate, aromatic aldehydes, and ureas as building blocks to generate a set of 3,4-dihydropyrimidine-5-carboxylic acid thiol esters. These thiol esters serve as starting materials for a subsequent Pd-catalyzed Cu-mediated Liebeskind-Srogl cross-coupling reaction with boronic acids to provide the desired 5-aroyl-3,4-dihydropyrimidin-2-one derivatives. Both steps were performed using microwave heating in sealed vessels, either in an automated sequential or parallel format using dedicated microwave reactor instrumentation. A diverse library of 30 5-aroyl-3,4-dihydropyrimidin-2-ones was prepared with commercially available aldehyde, urea, and boronic acid building blocks as starting materials.
Pisani
Leonardo
L
Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Prokopcová
Hana
H
Kremsner
Jennifer M
JM
Kappe
C Oliver
CO
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008872:Microwaves; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects*; D013237:Stereoisomerism
D011744:Pyrimidinones