[Tetrazoyl-11C]LY202157 synthesis for in vivo studies of the NMDA receptor channel complex

[Tetrazoyl- 11 C]LY202157 8 was prepared via a three step synthesis from ethyl (3S,4aR,6S,8aR)-6-bromomethyl-2-methoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 4. This bromo precursor was reacted with [ 11 C]hydrogen cyanide affording the corresponding [ 11 C]nitrile. Conversion to the tetrazole was achieved by treatment with azidotributyltin followed by hydrolysis with 6N hydrochloric acid at 200°C. After HPLC purification and analytical HPLC control, more than 370 MBq (10 mCi) of [tetrazoyl- 11 C] LY202157 were obtained after an overall 60 minute synthesis time with 38% yield (EOB) and specific activity of 25.9 GBq/μmol (700 mCi/μmol). Ex vivo biological studies showed that the [tetrazoyl- 11 C] LY202157 did not cross the brain blood barrier.