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...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020
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| Online Access: | https://hdl.handle.net/1721.1/125949 |
| _version_ | 1811097832081326080 |
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| author | Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo-Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo-Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F |
| author_sort | Ziegler, Robert E. |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T17:05:39Z |
| format | Article |
| id | mit-1721.1/125949 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:05:39Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1259492022-10-03T10:22:26Z 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 Massachusetts Institute of Technology. Department of Chemistry 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. 2020-06-23T19:06:21Z 2020-06-23T19:06:21Z 2018-06 2019-12-18T17:02:26Z Article http://purl.org/eprint/type/JournalArticle 1521-3773 https://hdl.handle.net/1721.1/125949 Ziegler, Robert E., et al., "7-step flow synthesis of the HIV integrase inhibitor Dolutegravir." Angewandte Chemie International Edition 57, 24 (June 2018): p. 7181-85 doi 10.1002/ANIE.201802256 ©2018 Author(s) en 10.1002/ANIE.201802256 Angewandte Chemie International Edition Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Wiley Wiley |
| spellingShingle | 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 |
| url | https://hdl.handle.net/1721.1/125949 |
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