Novel synthesis of ¹¹C-labeled imidazolines via Pd(0)-mediated ¹¹C-carbomethoxylation using [¹¹C]CO and arylborons

A labeling technique was developed for the imidazoline I-2 receptor ligand 2-(3-fluoro-tolyl)-4, 5-dihydro-1H-imidazole (FTIMD) using Pd(0)-mediated (11) C-carbomethoxylation with [(11) C]CO, followed by imidazoline ring formation with ethylenediamine-trimethylaluminium (EDA-AlMe3 ). To achieve this, [(11) C]CO was passed through a methanol (MeOH) solution containing 3-fluoro-4-methylphenylboronic acid (1), palladium (II) acetate (Pd [OAc](2) ), triphenylphosphine (PPh3 ), and p-benzoquinone (PBQ). The mixture was then heated at 65 degrees C for 5 min. EDA was introduced into the reaction mixture, and MeOH was completely evaporated at temperatures exceeding 100 degrees C. The dried reaction mixture was combined with an EDA-AlMe (1:1) toluene solution and heated at 145 degrees C for 10 min. Portions of the reaction mixture were analyzed through high-performance liquid chromatography, resulting in [(11) C]FTIMD with 26% (n = 2) decay-corrected radiochemical yield (RCY). This method could be utilized for various arylborons to produce [2-(11) C]imidazolines 4a-h with RCYs ranging from low to moderate. Notably, [2-(11) C]benazoline was obtained with a moderate RCY of 65%. The proposed technique serves as an alternative to the Grignard method, which uses [(11) C]CO to generate a [2-(11) C]-labeled imidazoline ring.