Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [11C]ibrutinib through 11C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [11C]CO, iodoethylene, and palladium–NiXantphos. [11C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; n = 9, relative to starting [11C]CO2), radiochemical purity >99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [11C]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.

The synthesis and isolation of N-imidazol-2ylidene-N′-p-tolylureate and thioureate proligands is described. Titanium(IV), nickel(II), and palladium(II) complexes containing one or two equivalents of the ligand were prepared by transmetalation of the ureate or thioureate salts. The X-ray structure of titanium complexes corroborated our prediction based on spectroscopic data and showed the ureate binds in a bidentate fashion through the oxygen and nitrogen atoms of the isocyanate building block, leaving the imidazol-2-imine fragment uncoordinated. Carbon−nitrogen bond lengths indicate substantial electron delocalization from the imidazole ring to the ureate group. In contrast, the ligand adopts a different coordination mode and binds to nickel and palladium through the N imidazol-2-ylidene and N p-tolyl atoms. Surprisingly, despite the softer nature of sulfur, coordination of the thioureate was exclusively through the sulfur and nitrogen atoms of the isothiocyanate building block with all three metals studied. All complexes were tested for ethylene polymerization at ambient conditions using methylaluminoxane as cocatalyst. Titanium(IV) complexes were found to be the most active, with activities up to 60 kg PE mol −1 catalyst h −1 .