The synthesis of non-exchangeable deuterated internal standards for imipramine and its metabolites

Article abstract of DOI:10.1002/jlcr.2580160212

The synthesis of 10,11-dihydro-5-(3-dimethylaminopropyl)-5H-dibenz[b,f]azepine (imipramine) and its 3-methylamino analogue (desipramine) labelled with deuterium in either the 1- or the 3-position of the side chain in high isotopic purity is described. The 3,3-d₂ compounds are obtained from the common precursor 5-(2-cyanoethyl)-10, 11-dihydro-5H-dibenz[b,f]azepine by reduction and alkylation, while the 1,1-d₂ products are accessible from the 5-(3-chloropropionyl) derivative by amination and reduction. These compounds are required for use as non-exchangeable mass spectrometric stable isotope internal standards for the simultaneous determination of imipramine and desipramine in biological fluids.