ABSTRACT
An efficient and rapid solution phase combinatorial synthesis of a 3-substituted 5-arylidene-1-methyl-2-thiohydantoin library was developed. The salient feature for this library production procedure is the addition of the Lewis acid catalyst, indium(III) trifluoromethanesulfonate, which serves to facilitate the direct condensation of aldehydes with 3-substituted 1-methyl-2-thiohydantoins. Use of this Lewis acid catalyst has resulted in faster reaction times, higher conversions and better purity profiles for these condensation reactions as compared to traditional uncatalyzed reactions. The resulting 315 member library of 3-substituted 5-arylidene-1-methyl-2-thiohydantoin is described.
Subject(s)
Organometallic Compounds/chemistry , Thiohydantoins/chemical synthesis , Aldehydes/chemistry , Catalysis , Models, ChemicalABSTRACT
The pyrazolo[1,5-a]pyrimidine class of compounds has been identified as a privileged structure for library synthesis on the basis of several key characteristics of the core molecule. A chemical set in excess of 400 compounds was synthesized to give 3,6,7-substituted pyrazolo[1,5-a]pyrimidinecarboxamides 9. To facilitate the rapid preparation of this library, a preparative strategy included the synthesis of activated p-nitrophenyl esters, followed by subsequent scavenging of the p-nitrophenol leaving group. Excess reagents were also removed using scavenging reagents that were found to be compatible with the synthetic methodology and that afforded target compounds in acceptable purity and yields.
