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7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033037/ https://www.ncbi.nlm.nih.gov/pubmed/29756689 http://dx.doi.org/10.1002/anie.201802256 |
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author | Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo‐Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F. |
author_facet | Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo‐Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F. |
author_sort | Ziegler, Robert E. |
collection | PubMed |
description | Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one‐step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput. |
format | Online Article Text |
id | pubmed-6033037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60330372018-07-12 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo‐Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F. Angew Chem Int Ed Engl Communications Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one‐step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput. John Wiley and Sons Inc. 2018-05-14 2018-06-11 /pmc/articles/PMC6033037/ /pubmed/29756689 http://dx.doi.org/10.1002/anie.201802256 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo‐Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F. 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title_full | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title_fullStr | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title_full_unstemmed | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title_short | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
title_sort | 7‐step flow synthesis of the hiv integrase inhibitor dolutegravir |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033037/ https://www.ncbi.nlm.nih.gov/pubmed/29756689 http://dx.doi.org/10.1002/anie.201802256 |
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