Microwave-assisted solution phase synthesis of dihydropyrimidine C5 amides and esters

摘要

Multifunctionalized dihydropyrimidine-5-carboxylicimides and esters are generated in a multistep sequence integrating a variety of enabling and high throughput technologies such as automated or parallel microwave synthesis, the use of poly mer-supported reagents, fluorous synthesis and purification strategies, and a continuous flow hydrogenation system. The key dihydropyrimidine-5-carboxylic acid intermediates are obtained in two steps by Biginelli multicomponent condensation of benzyl or allyl beta-ketoesters with aldehydes and urea/thioureas, followed by suitable benzyl or allyl deprotection strategies. Further functionalization of the acid cores with amines using polymer-supported coupling reagents or with alcohols utilizing Mitsunobu chemistry provides the desired amides or esters, respectively. (c) 2006 Elsevier Ltd. All rights reserved.