Evaluation and improvement of CuI-mediated C-cyanation.

CuI-mediated C-cyanation was evaluated by synthesizing [ C]perampanel ([ C]5) as a model compound and compared with previous reports. To a DMF solution with 5'-(2-bromophenyl)-1'-phenyl-[2,3'-bipyridin]-6'(1'H)-one (4) and CuI, [ C]NH CN in a stream of ammonia/nitrogen (5:95, v/v) gas was bubbled. Subsequently, the reaction mixture was heated at 180°C for 5 min. After HPLC purification, [ C]5 was obtained in 7.2 ± 1.0% (n = 4) non-decay corrected radiochemical yield with >99% radiochemical purity and a molar activity of 98 ± 28 GBq/μmol. In vivo evaluations of [ C]5 were performed using small animals. PET scans to check the kinetics of [ C]5 in the whole body of mice suggested that [ C]5 spreads rapidly into the brain, heart, and lungs and then accumulates in the small intestine. To evaluate the performance of CuI-mediated C-cyanation reaction, bromobenzene (6a) was selected as the model compound; however, it failed. Therefore, optimization of the reaction conditions has been performed, and consequently, the addition of K CO and prolonging the reaction time improved the radiochemical yield about double. With this improved method, CuI-mediated C-cyanation of various (hetero)aromatic bromides was performed to exhibit the tolerance of most functional groups and to provide C-cyanated products in good to moderate radiochemical yields.