Synthesis of substituted ( C)ureas and (~(11)C)sulphonylureas by Rh(l)-mediated carbonylation

摘要

The urea moiety is present in many biologically active compounds and thus an attractive target for ~(1)C-labelling. To extend the scope of the rhodium(l)-mediated carbonylative cross-coupling reaction between an azide and an amine and investigate its tolerance for functional groups, we have synthesized eight ureas and two sulphonylureas that were ~(11)c-labelled in the carbonyl position. The decay-corrected analytical radiochemical yields were in the range of 14-96% (from [~(11)Clcarbon monoxide). For example: starting from 1.33 GBq [~(11)Ckarbon monoxide, 0.237 GBq (66%) of the cytotoxic sulphonylurea [~(11)C]LY-181984 11 was isolated within 60min from end of bombardment. The mild reaction conditions and generality regarding functional groups of this method make it an attractive alternative to the [~(11)Cphosgene method for the synthesis of ~(11)C-labelled ureas.