Development of a Commercial Process for Odalasvir
Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. O...
Gespeichert in:
| Veröffentlicht in: | Organic process research & development 2022-03, Vol.26 (3), p.832-848 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 848 |
|---|---|
| container_issue | 3 |
| container_start_page | 832 |
| container_title | Organic process research & development |
| container_volume | 26 |
| creator | Tran, Duc N Zhdanko, Alexander Barroso, Santiago Nieste, Patrick Rahmani, Ramdane Holan, Jan Hoefnagels, Roel Reniers, Peter Vermoortele, Frederik Duguid, Stewart Cazanave, Lionel Figlus, Marek Muir, Colin Elliott, Alain Zhao, Peichao Paden, Warren Diaz, Cristina Hernandez Bell, Stephen J Hashimoto, Akihiro Phadke, Avinash Wiles, Jason A Vogels, Ilse Farina, Vittorio |
| description | Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ∼100 kg batches without issues. |
| doi_str_mv | 10.1021/acs.oprd.1c00237 |
| format | Article |
| fullrecord | <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_acs_oprd_1c00237</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>b114042011</sourcerecordid><originalsourceid>FETCH-LOGICAL-a280t-24e66caf149f4d716509eef761013e50954e704713946a4500a8a9b0e703d1963</originalsourceid><addsrcrecordid>eNp1j8tOwzAQRS0EEqWwZ-kPIGUmfiRZovCUKpUFSOws44ylVEkd2aUSf4-jdstq7jzu1RzGbhFWCCXeW5dWYYrdCh1AKaoztkBVQqFq_XWeNdSi0Kjhkl2ltAUApbFcMHykAw1hGmm358Fzy9swjhRdbwf-HoOjlLgPkW86O9h06OM1u_B2SHRzqkv2-fz00b4W683LW_uwLmxZw74oJWntrEfZeNlVqBU0RL7SCCgoN0pSBbJC0UhtpQKwtW2-IQ9Fh40WSwbHXBdDSpG8mWI_2vhrEMyMbDKymZHNCTlb7o6WebMNP3GXH_z__A-BZFil</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Development of a Commercial Process for Odalasvir</title><source>ACS Publications</source><creator>Tran, Duc N ; Zhdanko, Alexander ; Barroso, Santiago ; Nieste, Patrick ; Rahmani, Ramdane ; Holan, Jan ; Hoefnagels, Roel ; Reniers, Peter ; Vermoortele, Frederik ; Duguid, Stewart ; Cazanave, Lionel ; Figlus, Marek ; Muir, Colin ; Elliott, Alain ; Zhao, Peichao ; Paden, Warren ; Diaz, Cristina Hernandez ; Bell, Stephen J ; Hashimoto, Akihiro ; Phadke, Avinash ; Wiles, Jason A ; Vogels, Ilse ; Farina, Vittorio</creator><creatorcontrib>Tran, Duc N ; Zhdanko, Alexander ; Barroso, Santiago ; Nieste, Patrick ; Rahmani, Ramdane ; Holan, Jan ; Hoefnagels, Roel ; Reniers, Peter ; Vermoortele, Frederik ; Duguid, Stewart ; Cazanave, Lionel ; Figlus, Marek ; Muir, Colin ; Elliott, Alain ; Zhao, Peichao ; Paden, Warren ; Diaz, Cristina Hernandez ; Bell, Stephen J ; Hashimoto, Akihiro ; Phadke, Avinash ; Wiles, Jason A ; Vogels, Ilse ; Farina, Vittorio</creatorcontrib><description>Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ∼100 kg batches without issues.</description><identifier>ISSN: 1083-6160</identifier><identifier>EISSN: 1520-586X</identifier><identifier>DOI: 10.1021/acs.oprd.1c00237</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>Organic process research & development, 2022-03, Vol.26 (3), p.832-848</ispartof><rights>2021 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a280t-24e66caf149f4d716509eef761013e50954e704713946a4500a8a9b0e703d1963</citedby><cites>FETCH-LOGICAL-a280t-24e66caf149f4d716509eef761013e50954e704713946a4500a8a9b0e703d1963</cites><orcidid>0000-0001-7402-6914 ; 0000-0001-7864-2730</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.oprd.1c00237$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.oprd.1c00237$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids></links><search><creatorcontrib>Tran, Duc N</creatorcontrib><creatorcontrib>Zhdanko, Alexander</creatorcontrib><creatorcontrib>Barroso, Santiago</creatorcontrib><creatorcontrib>Nieste, Patrick</creatorcontrib><creatorcontrib>Rahmani, Ramdane</creatorcontrib><creatorcontrib>Holan, Jan</creatorcontrib><creatorcontrib>Hoefnagels, Roel</creatorcontrib><creatorcontrib>Reniers, Peter</creatorcontrib><creatorcontrib>Vermoortele, Frederik</creatorcontrib><creatorcontrib>Duguid, Stewart</creatorcontrib><creatorcontrib>Cazanave, Lionel</creatorcontrib><creatorcontrib>Figlus, Marek</creatorcontrib><creatorcontrib>Muir, Colin</creatorcontrib><creatorcontrib>Elliott, Alain</creatorcontrib><creatorcontrib>Zhao, Peichao</creatorcontrib><creatorcontrib>Paden, Warren</creatorcontrib><creatorcontrib>Diaz, Cristina Hernandez</creatorcontrib><creatorcontrib>Bell, Stephen J</creatorcontrib><creatorcontrib>Hashimoto, Akihiro</creatorcontrib><creatorcontrib>Phadke, Avinash</creatorcontrib><creatorcontrib>Wiles, Jason A</creatorcontrib><creatorcontrib>Vogels, Ilse</creatorcontrib><creatorcontrib>Farina, Vittorio</creatorcontrib><title>Development of a Commercial Process for Odalasvir</title><title>Organic process research & development</title><addtitle>Org. Process Res. Dev</addtitle><description>Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ∼100 kg batches without issues.</description><issn>1083-6160</issn><issn>1520-586X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1j8tOwzAQRS0EEqWwZ-kPIGUmfiRZovCUKpUFSOws44ylVEkd2aUSf4-jdstq7jzu1RzGbhFWCCXeW5dWYYrdCh1AKaoztkBVQqFq_XWeNdSi0Kjhkl2ltAUApbFcMHykAw1hGmm358Fzy9swjhRdbwf-HoOjlLgPkW86O9h06OM1u_B2SHRzqkv2-fz00b4W683LW_uwLmxZw74oJWntrEfZeNlVqBU0RL7SCCgoN0pSBbJC0UhtpQKwtW2-IQ9Fh40WSwbHXBdDSpG8mWI_2vhrEMyMbDKymZHNCTlb7o6WebMNP3GXH_z__A-BZFil</recordid><startdate>20220318</startdate><enddate>20220318</enddate><creator>Tran, Duc N</creator><creator>Zhdanko, Alexander</creator><creator>Barroso, Santiago</creator><creator>Nieste, Patrick</creator><creator>Rahmani, Ramdane</creator><creator>Holan, Jan</creator><creator>Hoefnagels, Roel</creator><creator>Reniers, Peter</creator><creator>Vermoortele, Frederik</creator><creator>Duguid, Stewart</creator><creator>Cazanave, Lionel</creator><creator>Figlus, Marek</creator><creator>Muir, Colin</creator><creator>Elliott, Alain</creator><creator>Zhao, Peichao</creator><creator>Paden, Warren</creator><creator>Diaz, Cristina Hernandez</creator><creator>Bell, Stephen J</creator><creator>Hashimoto, Akihiro</creator><creator>Phadke, Avinash</creator><creator>Wiles, Jason A</creator><creator>Vogels, Ilse</creator><creator>Farina, Vittorio</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-7402-6914</orcidid><orcidid>https://orcid.org/0000-0001-7864-2730</orcidid></search><sort><creationdate>20220318</creationdate><title>Development of a Commercial Process for Odalasvir</title><author>Tran, Duc N ; Zhdanko, Alexander ; Barroso, Santiago ; Nieste, Patrick ; Rahmani, Ramdane ; Holan, Jan ; Hoefnagels, Roel ; Reniers, Peter ; Vermoortele, Frederik ; Duguid, Stewart ; Cazanave, Lionel ; Figlus, Marek ; Muir, Colin ; Elliott, Alain ; Zhao, Peichao ; Paden, Warren ; Diaz, Cristina Hernandez ; Bell, Stephen J ; Hashimoto, Akihiro ; Phadke, Avinash ; Wiles, Jason A ; Vogels, Ilse ; Farina, Vittorio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a280t-24e66caf149f4d716509eef761013e50954e704713946a4500a8a9b0e703d1963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tran, Duc N</creatorcontrib><creatorcontrib>Zhdanko, Alexander</creatorcontrib><creatorcontrib>Barroso, Santiago</creatorcontrib><creatorcontrib>Nieste, Patrick</creatorcontrib><creatorcontrib>Rahmani, Ramdane</creatorcontrib><creatorcontrib>Holan, Jan</creatorcontrib><creatorcontrib>Hoefnagels, Roel</creatorcontrib><creatorcontrib>Reniers, Peter</creatorcontrib><creatorcontrib>Vermoortele, Frederik</creatorcontrib><creatorcontrib>Duguid, Stewart</creatorcontrib><creatorcontrib>Cazanave, Lionel</creatorcontrib><creatorcontrib>Figlus, Marek</creatorcontrib><creatorcontrib>Muir, Colin</creatorcontrib><creatorcontrib>Elliott, Alain</creatorcontrib><creatorcontrib>Zhao, Peichao</creatorcontrib><creatorcontrib>Paden, Warren</creatorcontrib><creatorcontrib>Diaz, Cristina Hernandez</creatorcontrib><creatorcontrib>Bell, Stephen J</creatorcontrib><creatorcontrib>Hashimoto, Akihiro</creatorcontrib><creatorcontrib>Phadke, Avinash</creatorcontrib><creatorcontrib>Wiles, Jason A</creatorcontrib><creatorcontrib>Vogels, Ilse</creatorcontrib><creatorcontrib>Farina, Vittorio</creatorcontrib><collection>CrossRef</collection><jtitle>Organic process research & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tran, Duc N</au><au>Zhdanko, Alexander</au><au>Barroso, Santiago</au><au>Nieste, Patrick</au><au>Rahmani, Ramdane</au><au>Holan, Jan</au><au>Hoefnagels, Roel</au><au>Reniers, Peter</au><au>Vermoortele, Frederik</au><au>Duguid, Stewart</au><au>Cazanave, Lionel</au><au>Figlus, Marek</au><au>Muir, Colin</au><au>Elliott, Alain</au><au>Zhao, Peichao</au><au>Paden, Warren</au><au>Diaz, Cristina Hernandez</au><au>Bell, Stephen J</au><au>Hashimoto, Akihiro</au><au>Phadke, Avinash</au><au>Wiles, Jason A</au><au>Vogels, Ilse</au><au>Farina, Vittorio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a Commercial Process for Odalasvir</atitle><jtitle>Organic process research & development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2022-03-18</date><risdate>2022</risdate><volume>26</volume><issue>3</issue><spage>832</spage><epage>848</epage><pages>832-848</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ∼100 kg batches without issues.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.oprd.1c00237</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-7402-6914</orcidid><orcidid>https://orcid.org/0000-0001-7864-2730</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1083-6160 |
| ispartof | Organic process research & development, 2022-03, Vol.26 (3), p.832-848 |
| issn | 1083-6160 1520-586X |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_acs_oprd_1c00237 |
| source | ACS Publications |
| title | Development of a Commercial Process for Odalasvir |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T21%3A37%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20a%20Commercial%20Process%20for%20Odalasvir&rft.jtitle=Organic%20process%20research%20&%20development&rft.au=Tran,%20Duc%20N&rft.date=2022-03-18&rft.volume=26&rft.issue=3&rft.spage=832&rft.epage=848&rft.pages=832-848&rft.issn=1083-6160&rft.eissn=1520-586X&rft_id=info:doi/10.1021/acs.oprd.1c00237&rft_dat=%3Cacs_cross%3Eb114042011%3C/acs_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |