||「Development of efficient construction of [11C]carbamate moiety using [11C] COCl2」
Fujinaga, Masayuki ,
Ogawa, Masanao ,
Kumata, Katsushi ,
Shimoda, Yoko ,
Kawamura, KazunoriMing-Rong, Zhang
Objectives: [11C]Phosgene ([11C]COCl2) is an important 11C-labeling reagent for synthesizing various radioactivecompounds containing a [11C]urea or [11C]carbamate moiety. We have developed several 11C-labeled lignadscontaining carbamate or unsymmetrical urea moiety using [11C]COCl2 and reported the synthesis of [11C]1 as anovel PET ligand for imaging of fatty acid amide hydrolase using [11C]COCl2 or [11C]CO2 . However, the synthesisof [11C]1 had some problems in poor reactivity and reproducibility. In this study, we developed a method forsynthesizing [11C]1-3 via 2 routes, starting from several phenol derivatives and base, to improve the reproducibilityand versatility for constructing the [11C]carbamate moiety.Methods: The alkylamine 10 was prepared from commercialy available materials. [11C]1-3 were synthesized byreaction of phenol derivatives with [11C]COCl2 in the presence of various bases, followed by reaction with amine 10,via 2 routes as shown in Scheme 1.Results: In the case of route A, when Et3N, DMAP, pyridine, or DBU was used, [11C]1 was obtained with moderateyield but [11C]2 or [11C]3 could not be obtained because 8 or 9 was formed at low yields. Instead of these bases,when 1,2,2,6,6-pentamethylpiperidine was used, 7-9 were produced in 68%, 88%, and 91% yields, which weredetermined by analyzing the reaction mixtures using radio-HPLC. However, following reaction of 8 or 9 with 10 did notproceed. In the case of route B, when 1,2,2,6,6-pentamethylpiperidine was used, after [11C]COCl2 was trapped to thereaction mixture, immediate addition of amine 10 to the mixture accomplished the reaction. After the two-stepsreaction, it was found that [11C]1-3 were produced with 92%, 82%, and 68% yields in the mixtures.Conclusions: We succeeded in improvement of reaction efficiency of [11C]1-3. These results showed that utilization of1,2,2,6,6-pentamethylpiperadine was more effective for constructing the [11C]carbamate moiety compared to otherbases, such as Et3N, DBU, and DMAP.References:  Fujinaga M, et al. (2013) J Label Compd Radiopharm, 56, S92.  Kumata K, et al. (2015) ACSChemical Neuroscience.
21st International Symposium on Radiopharmaceutical Sciences