Palladium-mediated oxidative carbonylation reactions for the synthesis of ¹¹C-radiolabelled ureas

Palladium(II)-mediated oxidative carbonylation reactions have been used to synthesize C-radiolabelled ureas via the coupling of amines with [C]carbon monoxide, in a one-pot process. Following trapping of CO in a solution of copper(I) tris(3,5-dimethylpyrazolyl)borate, homocoupling reactions of primary aliphatic amines proceed in the presence of Pd(PPh)Cl to give the corresponding N,N-disubstituted [C]ureas. Secondary amines do not produce the corresponding N,N,N,N-tetrasubsituted [C]ureas under these conditions. This difference in reactivity allows for the formation of unsymmetrical N,N',N'-trisubstituted [C]ureas using a mixture of a primary amine and a reactive secondary amine. The potential use of this method in positron emission tomography (PET) was demonstrated by the synthesis of the M1 muscarinic acetylcholine receptor radiotracer, [C-carbonyl]GSK1034702.