Synthesis of Deuterium-labeled Desipramine through Acid-catalyzed Exchange Reactions and the Stability of Deuterium Labeling

Abstract

Synthesis of three forms of selectively duterated desipramine with high isotopic purity through acid-catalyzed hydrogen-deuterium exchange reactions and the stability of deuterium labeling are described. Deuterated desipramine labeled at positions 2, 4, 6 and 8 [DMI-d₄ (I) ] was prepared directly by heating desipramine in 10% DCl-D₂O at 80°C for 8 hours. Desipramine labeled at all eight aromatic positions (DMI-d₈) was synthesized from iminodibenzyl-1, 2, 3, 4, 6, 7, 8, 9-d₈. Desipramine labeled at positions 1, 3, 7 and 9 [DMI-d₄ (II) ] was obtained by the “back-exchange” of DM1 d₈ under the protio condition according to the exchange procedure of DMI-d₄ (I) . Deuterium atoms labeled at positions 2, 4, 6 and 8 of desipramine were eliminated rapidly in 1 N HCl at 80°C, but those labeled at positions 1, 3, 7 and 9 of desipramine were quite chemically stable.