Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications
Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−me...
Gespeichert in:
| Veröffentlicht in: | Organic process research & development 2009-09, Vol.13 (5), p.880-887 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 887 |
|---|---|
| container_issue | 5 |
| container_start_page | 880 |
| container_title | Organic process research & development |
| container_volume | 13 |
| creator | Alimardanov, Asaf Gontcharov, Alexander Nikitenko, Antonia Chan, Anita W Ding, Zhixian Ghosh, Mousumi Levent, Mahmut Raveendranath, Panolil Ren, Jianxin Zhou, Maotang Mahaney, Paige E McComas, Casey C Ashcroft, Joseph Potoski, John R |
| description | Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated. |
| doi_str_mv | 10.1021/op900141r |
| format | Article |
| fullrecord | <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_op900141r</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>c162523630</sourcerecordid><originalsourceid>FETCH-LOGICAL-a259t-9ed24fd6c54f2a1077594b9640342126d8ec1dae66eadd58f3b8dedb5e3c97fb3</originalsourceid><addsrcrecordid>eNptUMtOwzAQtBBIlMKBP_CFA4eA7SRuwq0qr0jlIbVI3CLH3hCj1I5sU6m_xtfhUoQ4cNnZ3ZkdrQahU0ouKGH00g4lITSjbg-NaM5Ikhf8dT_2pEgTTjk5REfevxNCck7ZCH3OhXuDZCFFD3ixMaEDrz22LRZ4AT3IoNeAK9PpRgfrtkSU4EfrYNAGhs7FipdOGD9YF8Bd4QeQnTDaBy3x1A_R4ttvZs0anNfWbKfKKNtrY-PxtbY9DvbvarqKKHppu0gJo_CzsxK8x9Vq6LUUIbr4Y3TQit7DyQ-O0cvtzXJ2n8yf7qrZdJ4IlpchKUGxrFVc5lnLBCWTSV5mTckzkmaMMq4KkFQJ4ByEUnnRpk2hQDU5pLKctE06Ruc7X-ms9w7aenB6JdympqTehl7_hh61ZzutkL5-tx_OxM_-0X0BBWyGXw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications</title><source>ACS_美国化学学会期刊（与NSTL共建）</source><creator>Alimardanov, Asaf ; Gontcharov, Alexander ; Nikitenko, Antonia ; Chan, Anita W ; Ding, Zhixian ; Ghosh, Mousumi ; Levent, Mahmut ; Raveendranath, Panolil ; Ren, Jianxin ; Zhou, Maotang ; Mahaney, Paige E ; McComas, Casey C ; Ashcroft, Joseph ; Potoski, John R</creator><creatorcontrib>Alimardanov, Asaf ; Gontcharov, Alexander ; Nikitenko, Antonia ; Chan, Anita W ; Ding, Zhixian ; Ghosh, Mousumi ; Levent, Mahmut ; Raveendranath, Panolil ; Ren, Jianxin ; Zhou, Maotang ; Mahaney, Paige E ; McComas, Casey C ; Ashcroft, Joseph ; Potoski, John R</creatorcontrib><description>Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.</description><identifier>ISSN: 1083-6160</identifier><identifier>EISSN: 1520-586X</identifier><identifier>DOI: 10.1021/op900141r</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>Organic process research & development, 2009-09, Vol.13 (5), p.880-887</ispartof><rights>Copyright © 2009 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a259t-9ed24fd6c54f2a1077594b9640342126d8ec1dae66eadd58f3b8dedb5e3c97fb3</citedby><cites>FETCH-LOGICAL-a259t-9ed24fd6c54f2a1077594b9640342126d8ec1dae66eadd58f3b8dedb5e3c97fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/op900141r$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/op900141r$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids></links><search><creatorcontrib>Alimardanov, Asaf</creatorcontrib><creatorcontrib>Gontcharov, Alexander</creatorcontrib><creatorcontrib>Nikitenko, Antonia</creatorcontrib><creatorcontrib>Chan, Anita W</creatorcontrib><creatorcontrib>Ding, Zhixian</creatorcontrib><creatorcontrib>Ghosh, Mousumi</creatorcontrib><creatorcontrib>Levent, Mahmut</creatorcontrib><creatorcontrib>Raveendranath, Panolil</creatorcontrib><creatorcontrib>Ren, Jianxin</creatorcontrib><creatorcontrib>Zhou, Maotang</creatorcontrib><creatorcontrib>Mahaney, Paige E</creatorcontrib><creatorcontrib>McComas, Casey C</creatorcontrib><creatorcontrib>Ashcroft, Joseph</creatorcontrib><creatorcontrib>Potoski, John R</creatorcontrib><title>Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications</title><title>Organic process research & development</title><addtitle>Org. Process Res. Dev</addtitle><description>Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.</description><issn>1083-6160</issn><issn>1520-586X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNptUMtOwzAQtBBIlMKBP_CFA4eA7SRuwq0qr0jlIbVI3CLH3hCj1I5sU6m_xtfhUoQ4cNnZ3ZkdrQahU0ouKGH00g4lITSjbg-NaM5Ikhf8dT_2pEgTTjk5REfevxNCck7ZCH3OhXuDZCFFD3ixMaEDrz22LRZ4AT3IoNeAK9PpRgfrtkSU4EfrYNAGhs7FipdOGD9YF8Bd4QeQnTDaBy3x1A_R4ttvZs0anNfWbKfKKNtrY-PxtbY9DvbvarqKKHppu0gJo_CzsxK8x9Vq6LUUIbr4Y3TQit7DyQ-O0cvtzXJ2n8yf7qrZdJ4IlpchKUGxrFVc5lnLBCWTSV5mTckzkmaMMq4KkFQJ4ByEUnnRpk2hQDU5pLKctE06Ruc7X-ms9w7aenB6JdympqTehl7_hh61ZzutkL5-tx_OxM_-0X0BBWyGXw</recordid><startdate>20090918</startdate><enddate>20090918</enddate><creator>Alimardanov, Asaf</creator><creator>Gontcharov, Alexander</creator><creator>Nikitenko, Antonia</creator><creator>Chan, Anita W</creator><creator>Ding, Zhixian</creator><creator>Ghosh, Mousumi</creator><creator>Levent, Mahmut</creator><creator>Raveendranath, Panolil</creator><creator>Ren, Jianxin</creator><creator>Zhou, Maotang</creator><creator>Mahaney, Paige E</creator><creator>McComas, Casey C</creator><creator>Ashcroft, Joseph</creator><creator>Potoski, John R</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20090918</creationdate><title>Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications</title><author>Alimardanov, Asaf ; Gontcharov, Alexander ; Nikitenko, Antonia ; Chan, Anita W ; Ding, Zhixian ; Ghosh, Mousumi ; Levent, Mahmut ; Raveendranath, Panolil ; Ren, Jianxin ; Zhou, Maotang ; Mahaney, Paige E ; McComas, Casey C ; Ashcroft, Joseph ; Potoski, John R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a259t-9ed24fd6c54f2a1077594b9640342126d8ec1dae66eadd58f3b8dedb5e3c97fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alimardanov, Asaf</creatorcontrib><creatorcontrib>Gontcharov, Alexander</creatorcontrib><creatorcontrib>Nikitenko, Antonia</creatorcontrib><creatorcontrib>Chan, Anita W</creatorcontrib><creatorcontrib>Ding, Zhixian</creatorcontrib><creatorcontrib>Ghosh, Mousumi</creatorcontrib><creatorcontrib>Levent, Mahmut</creatorcontrib><creatorcontrib>Raveendranath, Panolil</creatorcontrib><creatorcontrib>Ren, Jianxin</creatorcontrib><creatorcontrib>Zhou, Maotang</creatorcontrib><creatorcontrib>Mahaney, Paige E</creatorcontrib><creatorcontrib>McComas, Casey C</creatorcontrib><creatorcontrib>Ashcroft, Joseph</creatorcontrib><creatorcontrib>Potoski, John R</creatorcontrib><collection>CrossRef</collection><jtitle>Organic process research & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alimardanov, Asaf</au><au>Gontcharov, Alexander</au><au>Nikitenko, Antonia</au><au>Chan, Anita W</au><au>Ding, Zhixian</au><au>Ghosh, Mousumi</au><au>Levent, Mahmut</au><au>Raveendranath, Panolil</au><au>Ren, Jianxin</au><au>Zhou, Maotang</au><au>Mahaney, Paige E</au><au>McComas, Casey C</au><au>Ashcroft, Joseph</au><au>Potoski, John R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications</atitle><jtitle>Organic process research & development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2009-09-18</date><risdate>2009</risdate><volume>13</volume><issue>5</issue><spage>880</spage><epage>887</epage><pages>880-887</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.</abstract><pub>American Chemical Society</pub><doi>10.1021/op900141r</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1083-6160 |
| ispartof | Organic process research & development, 2009-09, Vol.13 (5), p.880-887 |
| issn | 1083-6160 1520-586X |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_op900141r |
| source | ACS_美国化学学会期刊（与NSTL共建） |
| title | Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T08%3A26%3A46IST&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=Large-Scale%20Synthesis%20of%20a%20Selective%20Inhibitor%20of%20the%20Norepinephrine%20Transporter:%20Mechanistic%20Aspects%20of%20Conversion%20of%20Indolinone%20Diol%20to%20Indolinone%20Aminoalcohol%20and%20Process%20Implications&rft.jtitle=Organic%20process%20research%20&%20development&rft.au=Alimardanov,%20Asaf&rft.date=2009-09-18&rft.volume=13&rft.issue=5&rft.spage=880&rft.epage=887&rft.pages=880-887&rft.issn=1083-6160&rft.eissn=1520-586X&rft_id=info:doi/10.1021/op900141r&rft_dat=%3Cacs_cross%3Ec162523630%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 |