Solid-Phase Synthesis of 4(5),1′,5′-Trisubstituted 2,4′-Biimidazoles

Abstract

A method for the synthesis of libraries of 4(5),1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. (1) A trivalent scaffold, 2-(5'-amino-4(5)-formyl-1H,1'H-2,4'-biimidazol-1'-yl)acetic acid, was first prepared in solution by a two-step synthesis from ethyl adenin-9-ylacetate and bromomalonaldehyde. The product was coupled to an amino acid loaded Wang resin and the formyl group was subsequently derivatized either by reductive amination, oximation, or hydrazone formation. The 5'-amino group of the resin-bound biimidazole was then acylated and the products were finally released from the resin and purified. 5'-Amino-2,4'-biimidazole offers a scaffold for lead compounds of drug discovery, possibly useful in finding leads for protein kinase inhibitors.