Intramolecular Friedel-Crafts Acylation of [C]Isocyanates Enabling the Radiolabeling of [carbonyl-C]DPQ.

α,β-aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short-lived (t=20.3 min), β-decaying carbon-11, which has prevented their application as positron emission tomography tracers. Herein, we developed, optimized, and applied a widely applicable, one-pot, quick, robust and automatable radiolabeling method for α,β-aromatic lactams starting from [C]CO using the reagent POCl⋅AlCl. This method proceeds via intramolecular Friedel-Crafts acylation of in situ formed [C]isocyanates and shows a broad substrate scope for the formation of five- and six-membered rings. We implemented our developed labeling method for the radiosynthesis of the potential PARP1 PET tracer [carbonyl-C]DPQ in a clinical radiotracer production facility following the standards of the European Pharmacopoeia.