Synthesis of 14C-labelled CGS 19755, a selective NMDA antagonist

✍ Scribed by Alban J. Allentoff; Mahesh Desai; Bohdan Markus; Timothy Duelfer

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 462 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199611)38:11<989::aid-jlcr922>3.0.co;2-m

✦ Synopsis

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