Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor
3-{4-[1-(2,6-Dichloro-4-trifluoromethylphenyl)pyrazolo]}-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([3H]TDF) the required intermediate, 3-{4-[1-(2,6...
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| Veröffentlicht in: | Journal of organic chemistry 2003-10, Vol.68 (21), p.8075-8079 |
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| container_title | Journal of organic chemistry |
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| creator | Sammelson, Robert E Casida, John E |
| description | 3-{4-[1-(2,6-Dichloro-4-trifluoromethylphenyl)pyrazolo]}-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([3H]TDF) the required intermediate, 3-{4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]}-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [3H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity. |
| doi_str_mv | 10.1021/jo034520z |
| format | Article |
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For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([3H]TDF) the required intermediate, 3-{4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]}-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. 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Org. Chem</addtitle><description>3-{4-[1-(2,6-Dichloro-4-trifluoromethylphenyl)pyrazolo]}-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([3H]TDF) the required intermediate, 3-{4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]}-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [3H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.</description><subject>Azirines - chemical synthesis</subject><subject>Azirines - chemistry</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>GABA Antagonists - chemical synthesis</subject><subject>GABA Antagonists - chemistry</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>Molecular Structure</subject><subject>Organic chemistry</subject><subject>Photoaffinity Labels - chemical synthesis</subject><subject>Photoaffinity Labels - chemistry</subject><subject>Preparations and properties</subject><subject>Pyrazoles - chemical synthesis</subject><subject>Pyrazoles - chemistry</subject><subject>Tritium</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE9vEzEQxa0K1KZ_DnwB5AtISF2w1551ckwjmiIiiNpwtsa7XuKyWae2VyL99LhK1FyYy2hmfvP09Ah5x9lnzkr-5dEzIaFkzydkxHMvqgmTb8iIsbIsRFmJM3Ie4yPLBQCn5IxLEKDGMCLrh12f1ja6SH1Lka6CS27YFAs0trPNNb112-B71xU3GF_mO_d73e3o0ifbp2u6XPvksW1d71LeBm8sbX2gWZPOpzdTem9ru00-XJK3LXbRXh36Bfl1-3U1uysWP-ffZtNFgVJCKoRqARrkislKcQNMYilFJY3i0jIuWtOoxqI0jTQ1IINKGGRWVfmlkmosLsjHvW62_TTYmPTGxdp2HfbWD1ErUDApQWTw0x6sg48x2FZvg9tg2GnO9Eus-jXWzL4_iA5mY5sjecgxAx8OAMYauzZgX7t45IBPxmKsMlfsOReT_ft6x_BHV0oo0Kvlg57PvrMFZ_f6x1EX65j9DKHP2f3H4D9u_5k3</recordid><startdate>20031017</startdate><enddate>20031017</enddate><creator>Sammelson, Robert E</creator><creator>Casida, John E</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20031017</creationdate><title>Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor</title><author>Sammelson, Robert E ; Casida, John E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a445t-37f55da1704671b504a24364b714e013fbd7dea4bd4bc5a0563ba0e76a1764783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Azirines - chemical synthesis</topic><topic>Azirines - chemistry</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>GABA Antagonists - chemical synthesis</topic><topic>GABA Antagonists - chemistry</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>Molecular Structure</topic><topic>Organic chemistry</topic><topic>Photoaffinity Labels - chemical synthesis</topic><topic>Photoaffinity Labels - chemistry</topic><topic>Preparations and properties</topic><topic>Pyrazoles - chemical synthesis</topic><topic>Pyrazoles - chemistry</topic><topic>Tritium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sammelson, Robert E</creatorcontrib><creatorcontrib>Casida, John E</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sammelson, Robert E</au><au>Casida, John E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2003-10-17</date><risdate>2003</risdate><volume>68</volume><issue>21</issue><spage>8075</spage><epage>8079</epage><pages>8075-8079</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><coden>JOCEAH</coden><abstract>3-{4-[1-(2,6-Dichloro-4-trifluoromethylphenyl)pyrazolo]}-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([3H]TDF) the required intermediate, 3-{4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]}-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [3H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>14535785</pmid><doi>10.1021/jo034520z</doi><tpages>5</tpages></addata></record> |
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| ispartof | Journal of organic chemistry, 2003-10, Vol.68 (21), p.8075-8079 |
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| subjects | Azirines - chemical synthesis Azirines - chemistry Chemistry Exact sciences and technology GABA Antagonists - chemical synthesis GABA Antagonists - chemistry Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Molecular Structure Organic chemistry Photoaffinity Labels - chemical synthesis Photoaffinity Labels - chemistry Preparations and properties Pyrazoles - chemical synthesis Pyrazoles - chemistry Tritium |
| title | Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor |
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