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      https://www.ias.ac.in/article/fulltext/jcsc/130/06/0072

    • Keywords

       

      Schizophrenia; anti-psychotic drugs; brexpiprazole; Buchwald–Hartwig amination; heterocycles; benzo[b]thiophen-4-ol.

    • Abstract

       

      Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has beensynthesized via an extremely concise and convergent route, which involves in essence two key C–N bondformation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiopheneand 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, whichwas effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps fromcommercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screeningof catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely1 mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—thestarting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole.

    • Author Affiliations

       

      A SRAVANTH KUMAR SAI GIRIDHAR SARMA KANDANUR SAIKAT SEN SRINIVAS ORUGANTI1

      1. Centre for Process Research and Innovation, Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telangana 500 046, India
    • Dates

       
    • Supplementary Material

       
  • Journal of Chemical Sciences | News

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