Efficient Synthesis of a GABAA α2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach
A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. T...
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| Veröffentlicht in: | Journal of organic chemistry 2005-07, Vol.70 (15), p.6034-6039 |
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| container_end_page | 6039 |
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| container_issue | 15 |
| container_start_page | 6034 |
| container_title | Journal of organic chemistry |
| container_volume | 70 |
| creator | Jensen, Mark S Hoerrner, R. Scott Li, Wenjie Nelson, Dorian P Javadi, Gary J Dormer, Peter G Cai, Dongwei Larsen, Robert D |
| description | A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described. |
| doi_str_mv | 10.1021/jo050741o |
| format | Article |
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Scott ; Li, Wenjie ; Nelson, Dorian P ; Javadi, Gary J ; Dormer, Peter G ; Cai, Dongwei ; Larsen, Robert D</creator><creatorcontrib>Jensen, Mark S ; Hoerrner, R. Scott ; Li, Wenjie ; Nelson, Dorian P ; Javadi, Gary J ; Dormer, Peter G ; Cai, Dongwei ; Larsen, Robert D</creatorcontrib><description>A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/jo050741o</identifier><identifier>CODEN: JOCEAH</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Chemistry ; Exact sciences and technology ; Heterocyclic compounds ; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings ; Organic chemistry ; Preparations and properties</subject><ispartof>Journal of organic chemistry, 2005-07, Vol.70 (15), p.6034-6039</ispartof><rights>Copyright © 2005 American Chemical Society</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jo050741o$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jo050741o$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16966337$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Jensen, Mark S</creatorcontrib><creatorcontrib>Hoerrner, R. Scott</creatorcontrib><creatorcontrib>Li, Wenjie</creatorcontrib><creatorcontrib>Nelson, Dorian P</creatorcontrib><creatorcontrib>Javadi, Gary J</creatorcontrib><creatorcontrib>Dormer, Peter G</creatorcontrib><creatorcontrib>Cai, Dongwei</creatorcontrib><creatorcontrib>Larsen, Robert D</creatorcontrib><title>Efficient Synthesis of a GABAA α2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach</title><title>Journal of organic chemistry</title><addtitle>J. Org. Chem</addtitle><description>A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.</description><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpFkc1O3DAURi1UJKYDC97Am-5q8M84iZdpGIZKVIw0Q7fWjWMXT904tTOI4a14kT4Tqajo3dzFPfdInz6Ezhm9YJSzy12kkpYLFo_QjElOSaHo4gOaUco5EbwQJ-hjzjs6jZRyhg5L57zxth_x5tCPDzb7jKPDgFf1l7rGf174Z0E2Nlgz-keL6xBiHm3yBn-L3T7AGBN-9DA9bOzv_eTxEPC6Iw2MEA7PtsNNijmTJu6H4PsfuB6GFME8nKJjByHbs397ju6vl9vmhtzerb429S0BLhYjaRVlTKkSWFVSJ6nilQXeVkaWwlErW-Nk17XCOmVbVxnHqKxAMKFsqSZazNGnN-8A2UBwCXrjsx6S_wXpoFmhikKIcuLIG-enfE_vd0g_dVGKUurteqOvFpxu11ffdfHfCybrXdynfkqhGdV_e9DvPYhXKLt6Jw</recordid><startdate>20050722</startdate><enddate>20050722</enddate><creator>Jensen, Mark S</creator><creator>Hoerrner, R. 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Scott ; Li, Wenjie ; Nelson, Dorian P ; Javadi, Gary J ; Dormer, Peter G ; Cai, Dongwei ; Larsen, Robert D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a234t-b9011997a1870f50928ea2b8c573f0e5bcf5ddb3ef9ebf8cf1058a3139e790923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jensen, Mark S</creatorcontrib><creatorcontrib>Hoerrner, R. Scott</creatorcontrib><creatorcontrib>Li, Wenjie</creatorcontrib><creatorcontrib>Nelson, Dorian P</creatorcontrib><creatorcontrib>Javadi, Gary J</creatorcontrib><creatorcontrib>Dormer, Peter G</creatorcontrib><creatorcontrib>Cai, Dongwei</creatorcontrib><creatorcontrib>Larsen, Robert D</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jensen, Mark S</au><au>Hoerrner, R. Scott</au><au>Li, Wenjie</au><au>Nelson, Dorian P</au><au>Javadi, Gary J</au><au>Dormer, Peter G</au><au>Cai, Dongwei</au><au>Larsen, Robert D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficient Synthesis of a GABAA α2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2005-07-22</date><risdate>2005</risdate><volume>70</volume><issue>15</issue><spage>6034</spage><epage>6039</epage><pages>6034-6039</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><coden>JOCEAH</coden><abstract>A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><doi>10.1021/jo050741o</doi><tpages>6</tpages></addata></record> |
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| source | American Chemical Society Journals |
| subjects | Chemistry Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Organic chemistry Preparations and properties |
| title | Efficient Synthesis of a GABAA α2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach |
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