Evaluation and improvement of CuI-mediated C-11-cyanation

CuI-mediated C-11-cyanation was evaluated by synthesizing [C-11]perampanel ([C-11]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-11]NH4CN in a stream of ammonia/nitrogen (5:95, v/v) gas was bubbled. Subsequently, the reaction mixture was heated at 180 degrees C for 5 min. After HPLC purification, [C-11]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/mu mol. In vivo evaluations of [C-11]5 were performed using small animals. PET scans to check the kinetics of [C-11]5 in the whole body of mice suggested that [C-11]5 spreads rapidly into the brain, heart, and lungs and then accumulates in the small intestine. To evaluate the performance of CuI-mediated C-11-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 K2CO3 and prolonging the reaction time improved the radiochemical yield about double. With this improved method, CuI-mediated C-11-cyanation of various (hetero)aromatic bromides was performed to exhibit the tolerance of most functional groups and to provide C-11-cyanated products in good to moderate radiochemical yields.