Synthesis of a radoilabeled type A cholecystokinin receptor antagonist, (R)-N-pentyl-N-(4,5-di[3H]pentyl)N(α)-(3-quinolinoyl)glutamic acid amide

Article abstract of DOI:10.1002/(SICI)1099-1344(200001)43:1<77::AID-JLCR292>3.0.CO;2-V

A method for the preparation of a radiolabeled CCK(A)-specific antagonist, (R)-N-pentyl-N-(4,5-di[³H]pentyl)N(α)-(3-quinolinoyl)glutamic acid amide, [³H]-A-65186, is described. (R)-γ-Benzyl-N-BOC-glutamic acid was coupled with N-(4-pentenyl)-N-pentylamine using BOPCl and TEA in dichloromethane to provide the corresponding amide. Deprotection of the α-amino moiety followed by coupling with 3-quinolinecarboxylic acid in the presence of EDCI, TEA, and HOBt in dichloromethane resulted in (R)-N-(4-pentenyl)-N-pentyl γ-benzyl-N(α)-(3-quinolinoyl)glutamic acid amide. Tritiation with concomitant hydrogenolysis of the benzyl ester proceeds smoothly to provide [³H]-A-65186.