The syntheses of isotopically labelled CB-1 antagonists for the treatment of obesity.

BMS-725519, BMS-811064, and BMS-812204 are potent and selective central cannabinoid receptor antagonists that have been investigated for the treatment of human obesity. To further understand their biotransformation profiles, radiolabelled and stable-labelled products were required. This paper describes the utility of [C-14] 1,1-carbonyldiimidazole as a radiolabelling reagent for the syntheses of carbonyl-labelled [C-14]BMS-725519, [C-14]BMS-811064, and [C-14]BMS-812204. The syntheses of stable-labelled [C-13(6)]BMS-725519 and [(CD3CD2)-C-13-C-13]BMS-812204 synthesized from of [C-13(6)]4-chloroacetophenone and [(CD3CD2)-C-13-C-13]iodoethane, respectively, are also described.