SYNTHESIS OF C-14-LABELED CGS-19755, A SELECTIVE NMDA ANTAGONIST

CGS 19755 is a selective NMDA (N-methyl-D-aspartate) antagonist presen tly under development as a neuronal protecting agent after stroke and head trauma. It was synthesized with C-14-labelling in the carboxylic acid side chain via the synthetic route displayed in Scheme 1. Key ste ps in the synthesis involved a Reissert-Henze addition of potassium [C -14]cyanide to a functionalized pyridine N-oxide, followed by hydrolys is and a selective hydrogenation affording the desired cis-substituted piperidine target. Using this procedure, [C-14]CGS 19755 was prepared with radiochemical purity of 99.6%. The synthesis demonstrates the ut ility of the Reissert-Henze reaction, in conjunction with palladium/rh odium-catalyzed hydrogenation, as a facile means of preparing C-14-lab elled cis-2,4-substituted cyclic amino acids.