The synthesis and X-ray structure of 3,7-diiododibenzosuberone. Synthesis of 3,7-diiodoamitriptyline

Abstract

The preparation of iodinated tricyclic antidepressive drug amitriptyline as the substrate for isotopic exchange labelling is described. Direct iodination of 10,11-dihydro-5H-dibenzo[a,d]-cycloheptene-5-one leads mainly to 3,7-diiododerivative (III). Its structure was confirmed by means of single crystal X-ray diffraction analysis: monoclinic, P21/c; a = 13.315(2), b = 7.852(1), c = 13.584(2) Å, β = 103.67(2)°, Z = 4, R = 0.064 for 2 474 observed independent reflections. Iodinated ketone was transformed to 3,7-diiodo-5-(3-N,N-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo[a,d]-cycloheptene (diiodoamitriptyline), by the reaction with dimethylaminopropylmagnesiumchloride and dehydration of the resulting alcohol. The product was isolated as hydrogen oxalate salt.