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...
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| Veröffentlicht in: | Angewandte Chemie 2018-06, Vol.130 (24), p.7299-7303 |
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| container_title | Angewandte Chemie |
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| creator | Ziegler, Robert E. Desai, Bimbisar K. Jee, Jo‐Ann Gupton, B. Frank Roper, Thomas D. Jamison, Timothy F. |
| 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.
So einfach wie D‐T‐G: Eine Strategie für die Durchflusssynthese des Anti‐HIV‐Wirkstoffs Dolutegravir in sieben Schritten mit drei diskreten Flussoperationen wird beschrieben. Die Studien führen zu einer kurzen Synthese des aktiven pharmazeutischen Inhaltsstoffs und zwei Beispielen von dreistufigen teleskopischen Flusssequenzen. |
| doi_str_mv | 10.1002/ange.201802256 |
| format | Article |
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So einfach wie D‐T‐G: Eine Strategie für die Durchflusssynthese des Anti‐HIV‐Wirkstoffs Dolutegravir in sieben Schritten mit drei diskreten Flussoperationen wird beschrieben. Die Studien führen zu einer kurzen Synthese des aktiven pharmazeutischen Inhaltsstoffs und zwei Beispielen von dreistufigen teleskopischen Flusssequenzen.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.201802256</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Amidierungen ; Chemical synthesis ; Chemistry ; Continuous flow ; Durchflussreaktoren ; HIV ; Human immunodeficiency virus ; Integrase ; Intermediates ; Mehrstufige Synthesen ; Organic chemistry ; Pyridone ; Rapid manufacturing ; Telescoping</subject><ispartof>Angewandte Chemie, 2018-06, Vol.130 (24), p.7299-7303</ispartof><rights>2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.</rights><rights>2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2026-6483eb841b0e5103e2dccbb5d93d50790c89c1a9d5506a717cf9d8b11f0b26403</citedby><cites>FETCH-LOGICAL-c2026-6483eb841b0e5103e2dccbb5d93d50790c89c1a9d5506a717cf9d8b11f0b26403</cites><orcidid>0000-0002-8601-7799</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.201802256$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.201802256$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Ziegler, Robert E.</creatorcontrib><creatorcontrib>Desai, Bimbisar K.</creatorcontrib><creatorcontrib>Jee, Jo‐Ann</creatorcontrib><creatorcontrib>Gupton, B. Frank</creatorcontrib><creatorcontrib>Roper, Thomas D.</creatorcontrib><creatorcontrib>Jamison, Timothy F.</creatorcontrib><title>7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir</title><title>Angewandte Chemie</title><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.
So einfach wie D‐T‐G: Eine Strategie für die Durchflusssynthese des Anti‐HIV‐Wirkstoffs Dolutegravir in sieben Schritten mit drei diskreten Flussoperationen wird beschrieben. Die Studien führen zu einer kurzen Synthese des aktiven pharmazeutischen Inhaltsstoffs und zwei Beispielen von dreistufigen teleskopischen Flusssequenzen.</description><subject>Amidierungen</subject><subject>Chemical synthesis</subject><subject>Chemistry</subject><subject>Continuous flow</subject><subject>Durchflussreaktoren</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Integrase</subject><subject>Intermediates</subject><subject>Mehrstufige Synthesen</subject><subject>Organic chemistry</subject><subject>Pyridone</subject><subject>Rapid manufacturing</subject><subject>Telescoping</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNqFkL1OwzAURi0EEqWwMltiTrl27Dgeq9I_qYKhwGrFjtOmCnGxU6psPALPyJOQUgQj0_10dc690ofQNYEBAaC3Wb2yAwokBUp5coJ6hFMSxYKLU9QDYCxKKZPn6CKEDQAkVMgeGonP949lY7d4Urk9XrZ1s7ahDNgVuEt4Nn_G87qxK58F26V1qcvGeXznqt339q30l-isyKpgr35mHz1Nxo-jWbR4mM5Hw0VkKNAkSlgaW50yosFyArGluTFa81zGOQchwaTSkEzmnEOSCSJMIfNUE1KApgmDuI9ujne33r3ubGjUxu183b1UFDhwEkvJOmpwpIx3IXhbqK0vXzLfKgLqUJQ6FKV-i-oEeRT2ZWXbf2g1vJ-O_9wvvwBr5w</recordid><startdate>20180611</startdate><enddate>20180611</enddate><creator>Ziegler, Robert E.</creator><creator>Desai, Bimbisar K.</creator><creator>Jee, Jo‐Ann</creator><creator>Gupton, B. Frank</creator><creator>Roper, Thomas D.</creator><creator>Jamison, Timothy F.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0002-8601-7799</orcidid></search><sort><creationdate>20180611</creationdate><title>7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir</title><author>Ziegler, Robert E. ; Desai, Bimbisar K. ; Jee, Jo‐Ann ; Gupton, B. Frank ; Roper, Thomas D. ; Jamison, Timothy F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2026-6483eb841b0e5103e2dccbb5d93d50790c89c1a9d5506a717cf9d8b11f0b26403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amidierungen</topic><topic>Chemical synthesis</topic><topic>Chemistry</topic><topic>Continuous flow</topic><topic>Durchflussreaktoren</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Integrase</topic><topic>Intermediates</topic><topic>Mehrstufige Synthesen</topic><topic>Organic chemistry</topic><topic>Pyridone</topic><topic>Rapid manufacturing</topic><topic>Telescoping</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ziegler, Robert E.</creatorcontrib><creatorcontrib>Desai, Bimbisar K.</creatorcontrib><creatorcontrib>Jee, Jo‐Ann</creatorcontrib><creatorcontrib>Gupton, B. Frank</creatorcontrib><creatorcontrib>Roper, Thomas D.</creatorcontrib><creatorcontrib>Jamison, Timothy F.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ziegler, Robert E.</au><au>Desai, Bimbisar K.</au><au>Jee, Jo‐Ann</au><au>Gupton, B. Frank</au><au>Roper, Thomas D.</au><au>Jamison, Timothy F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir</atitle><jtitle>Angewandte Chemie</jtitle><date>2018-06-11</date><risdate>2018</risdate><volume>130</volume><issue>24</issue><spage>7299</spage><epage>7303</epage><pages>7299-7303</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>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.
So einfach wie D‐T‐G: Eine Strategie für die Durchflusssynthese des Anti‐HIV‐Wirkstoffs Dolutegravir in sieben Schritten mit drei diskreten Flussoperationen wird beschrieben. Die Studien führen zu einer kurzen Synthese des aktiven pharmazeutischen Inhaltsstoffs und zwei Beispielen von dreistufigen teleskopischen Flusssequenzen.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.201802256</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-8601-7799</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Amidierungen Chemical synthesis Chemistry Continuous flow Durchflussreaktoren HIV Human immunodeficiency virus Integrase Intermediates Mehrstufige Synthesen Organic chemistry Pyridone Rapid manufacturing Telescoping |
| title | 7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir |
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