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Novel and facile process for the preparation of Brexpiprazole an antipsychotic drug

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Abstract

A novel and industrially viable process was developed to synthesize Brexpiprazole an antipsychotic drug. This process involves using 1,4-butanediol as a key starting material, which is then diprotected and subsequently reacted with 7-hydroxy-2(1H)-quinolinone and piperazine-l-benzo[b]thien-4-y1 hydrochloride using potassium carbonate as a base, resulting in a novel intermediate, the spiro-tosyl salt, with a good yield and purity. Various conditions, solvents and bases were evaluated to optimize the coupling reaction of tosyl salt with 7-Hydroxy-2-(1H)-Quinolinone. Finally, we have chosen Sodium carbonate as a base and selected N,N-dimethylacetamide as a solvent. The reaction was carried at an elevated temperature, resulting in the production of Brexpiprazole with good yield and excellent purity. The product is fully characterized by using analytical methods like 1H NMR, 13C NMR, HPLC and HRMS analysis.

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Full experimental details, IR, 1H NMR spectra, 13C NMR spectra and HRMS. This material can be found via the “Supplementary Content” section of this article’s webpage.

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Acknowledgements

The authors thank the management of Aurobindo Pharma Ltd., for granting permission to publish the work. The authors are also grateful to the Chemical and Analytical Research Departments of Aurobindo Pharma Ltd. for their support of our work.

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Authors and Affiliations

  1. Chemical Research and Development Department, APL Research Centre-II, Aurobindo Pharma Limited, Telangana State, Survey No. 71 and 72, Indrakaran Village, Kandi Mandal, Sangareddy District, 502329, India

    Deekonda Satheesh, Bhavanam Sekhara Reddy, Vaddi Pandu Ranga Rao, Ramadas Chavakula, B. Sreenivasulu & Anil Kumar Guduri

  2. Department of Inorganic and Analytical Chemistry, A.U. College of Science and Technology, Andhra University, Visakhapatnam, Andhra Pradesh, 530003, India

    Deekonda Satheesh & Keloth Basavaiah

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  1. Deekonda Satheesh
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  2. Bhavanam Sekhara Reddy
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  3. Keloth Basavaiah
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  4. Vaddi Pandu Ranga Rao
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  5. Ramadas Chavakula
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  6. B. Sreenivasulu
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Correspondence to Deekonda Satheesh.

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Satheesh, D., Reddy, B.S., Basavaiah, K. et al. Novel and facile process for the preparation of Brexpiprazole an antipsychotic drug. Chem. Pap. 78, 3017–3022 (2024). https://doi.org/10.1007/s11696-023-03289-y

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