Broad Scope and High-Yield Access to Unsymmetrical Acyclic [11C]Ureas for Biomedical Imaging from [11C]Carbonyl Difluoride

Effective methods are needed for labelling acyclic ureas with carbon-11 (t_1/2=20.4 min) as potential radiotracers for biomedical imaging with positron emission tomography (PET). Herein, we describe the rapid and high-yield syntheses of unsymmetrical acyclic ¹¹C]ureas under mild conditions (room temperature and within 7 min) using no-carrier-added ¹¹C]carbonyl difluoride with aliphatic and aryl amines. This methodology is compatible with diverse functionality (e. g., hydroxy, carboxyl, amino, amido, or pyridyl) in the substrate amines. The labelling process proceeds through putative ¹¹C]carbamoyl fluorides and for primary amines through isolable ¹¹C]isocyanate intermediates. Unsymmetrical ¹¹C]ureas are produced with negligible amounts of unwanted symmetrical ¹¹C]urea byproducts. Moreover, the overall labelling method tolerates trace water and the generally moderate to excellent yields show good reproducibility. ¹¹C]Carbonyl difluoride shows exceptional promise for application to the synthesis of acyclic ¹¹C]ureas as new radiotracers for biomedical imaging with PET.