Synthesis Of Aripiprazole And Benzo[b]thiophene Derivatives

The thesis is divided into two parts, dealing with the development of anindustrially applicable route for the synthesis of aripiprazole, a recentlymarketed drug for the treatment of schizophrenia and preparing a seriesbenzothiophene derivatives, which are of interest as building blocks to affordfocused library in drug lead screening. In the first part, a five-step synthetic route for aripiprazole is discussed.The efficient synthesis starts from 3- phenyl-propionic acid by a sequence ofreactions including nitration, reduction, conversion of the amino group to ahydroxyl group, alkylation and amine nucleophilic substitution in 30%overall yield. The final product was fully characterized by HPLC-MS, H 1NMR, elemental analysis IR, UV and DTA. In the second part, various 2-aryl substituted benzothiophenederivatives were constructed by cyclization reaction ofα-[(3-methoxyphenyl)thio]acetophenone in the presence of Lewis acids.Thus twenty 2,5-disubstituted benzothiophenes and the intermediates weresynthesized, and among these nine desired products have never beenreported. The widely application of benzothiophene analogs for thesynthesis of thioindigo dyes, pesticides and pharmaceutical integrands suchas antibiotics, analgesics, antiexudatives, antiinflammatories, diuretics andenzyme inhibitors makes the synthesized molecules of potential interest infurther study of the synthesized compounds.