Solid-phase synthesis of urea and amide libraries using the T2 triazene linker

Starting from Merrifield resin, primary amines were immobilized in two step s by triazene linkage (T2 linker). While reaction with isocyanates gave ris e to resin-bound urea derivatives, acylation by acid chlorides or anhydride s furnished amides bound to solid support via the nitrogen atom, therefore representing a novel backbone amide linker. Cleavage from the resin was con ducted using dilute trimethylsilyl chloride or trifluoroacetic acid, respec tively, to yield ureas and amines/amides in a library format (altogether 60 examples; manual synthesis: 17 ureas, 6 mono-alkylated ureas [including di hydroxylation and ozonolysis/Wittig reaction]; automated synthesis: 15 urea s, 15 amides) in high purities and good overall yields. The synthesis of a small library (4 x 4 member) was successfully conducted on a Bohdan Neptune synthesizer.