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

Palladium(II)‐mediated oxidative carbonylation reactions have been used to synthesize 11 C‐radiolabelled ureas via the coupling of amines with [ 11 C]carbon monoxide, in a one‐pot process. Following trapping of 11 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 3 ) 2 Cl 2 to give the corresponding N , N ‐disubstituted [ 11 C]ureas. Secondary amines do not produce the corresponding N , N , N , N ‐tetrasubsituted [ 11 C]ureas under these conditions. This difference in reactivity allows for the formation of unsymmetrical N , N ’, N ’‐trisubstituted [ 11 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, [ 11 C‐ carbonyl ]GSK1034702.