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

A method for the preparation of a radiolabeled CCKA-specific antagonist, (R )-N-pentyl-N-(4, 5-di[H-3]pentyl) N-alpha-(3-quinolinoyl)glutamic acid amid e, [H-3]-A-65186, is described. (R)-gamma-Benzyl-N-BOC-glutamic acid was co upled with N-(4-pentenyl)-N-pentylamine using BOPCl and TEA in dichlorometh ane to provide the corresponding amide. Deprotection of the alpha-amino moi ety followed by coupling with 3-quinolinecarboxylic acid in the presence of EDCI, TEA, and HOBt in dichloromethane resulted in (R)-N-(4-pentenyl)-N-pe ntyl gamma-benzyl-N-alpha-(3-quinolinoyl)glutamic acid amide. Tritiation wi th concomitant hydrogenolysis of the benzyl ester proceeds smoothly to prov ide [H-3]-A-65186.