Facile and high-yield synthesis of N-(4-diethylamino)benzyl-4-[11C]methoxy-N-(p-tolyl)benzenesulfonamide as a new potential PET selective CB2 radioligand

The reference standard N-(4-diethylamino)benzyl-4-methoxy-N-(p-tolyl)benzenesulfonamide (3c) (CB2, Ki=0.5 nM; CB1, Ki=1297 nM; selectivity CB1/CB2=2594) and its corresponding precursor N-(4-diethylamino)benzyl-4-hydroxy-N-(p-tolyl)benzenesulfonamide (3d) were synthesized from 4-(diethylamino)benzaldehyde and p-toluidine in 3 steps with 75-84% overall chemical yield. The target tracer N-(4-diethylamino)benzyl-4-[11C]methoxy-N-(p-tolyl)benzenesulfonamide ([11C]3c) was synthesized from the phenol hydroxyl precursor by O-[11C]-methylation with [11C]CH3OTf, followed by HPLC combined with SPE purification in 40-50% decay corrected radiochemical yields with 370-740 GBq/μmol specific activity at the end of bombardment (EOB).