Title:
METHOD FOR PREPARING META-TRIFLUOROMETHYLTHIO-, DIFLUOROMETHYLTHIO-, OR TRIFLUOROMETHYL-SUBSTITUTED PYRIDINE COMPOUND
Document Type and Number:
WIPO Patent Application WO/2023/216363
Kind Code:
A1
Abstract:
Provided is a method for preparing a meta-trifluoromethylthio-, difluoromethylthio-, or trifluoromethyl-substituted pyridine compound, comprising: S1, in a glove box filled with nitrogen, adding a catalyst, a solvent, pinacolborane and pyridine into a reaction flask, stirring, and reacting at 40-100 °C for 2-12 hours to give dihydropyridine; S2, adding a trifluoromethylthio reagent, a difluoromethylthio reagent, or a trifluoromethyl reagent into the reaction flask, stirring, and reacting for 2-12 hours at room temperature to 80 °C to give trifluoromethylthio-, difluoromethylthio-, or trifluoromethyl-substituted dihydropyridine; and S3, placing the reaction flask in the air or adding 2,3-dichloro-5,6-dicyanobenzoquinone, stirring, reacting at room temperature for 4-12 hours, evaporating at reduced pressure to remove the solvent, and separating by column chromatography to give the meta-substituted pyridine compound. The method features the absence of transition metal catalysts, mild reaction conditions, good selectivity, and broad functional group compatibility, and can be used for late-stage functional group modification of drug molecules.
Inventors:
WANG XIAOCHEN (CN)
ZHOU XINYUE (CN)
ZHOU XINYUE (CN)
Application Number:
PCT/CN2022/099346
Publication Date:
November 16, 2023
Filing Date:
June 17, 2022
Export Citation:
Assignee:
UNIV NANKAI (CN)
International Classes:
C07D213/16; C07D213/26; C07D213/70
Other References:
ARROWSMITH MERLE, HILL MICHAEL S., HADLINGTON TERRANCE, KOCIOK-KÖHN GABRIELE, WEETMAN CATHERINE: "Magnesium-Catalyzed Hydroboration of Pyridines", ORGANOMETALLICS, AMERICAN CHEMICAL SOCIETY, vol. 30, no. 21, 14 November 2011 (2011-11-14), pages 5556 - 5559, XP093048184, ISSN: 0276-7333, DOI: 10.1021/om2008138
FIONN O’HARA, DONNA G. BLACKMOND, PHIL S. BARAN: "Radical-Based Regioselective C–H Functionalization of Electron-Deficient Heteroarenes: Scope, Tunability, and Predictability", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 135, no. 32, 14 August 2013 (2013-08-14), pages 12122 - 12134, XP055675708, ISSN: 0002-7863, DOI: 10.1021/ja406223k
JIANG WU; YANG GU; XUEBING LENG; QILONG SHEN: "Copper‐Promoted Sandmeyer Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, HOBOKEN, USA, vol. 54, no. 26, 12 May 2015 (2015-05-12), Hoboken, USA, pages 7648 - 7652, XP072075412, ISSN: 1433-7851, DOI: 10.1002/anie.201502113
LARSEN MATTHEW A., HARTWIG JOHN F.: "Iridium-Catalyzed C–H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 136, no. 11, 19 March 2014 (2014-03-19), pages 4287 - 4299, XP093048185, ISSN: 0002-7863, DOI: 10.1021/ja412563e
ZHI‐YUN LIU; ZHI‐HUI WEN; XIAO‐CHEN WANG: "B(C6F5)3‐Catalyzed Cascade Reduction of Pyridines", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, HOBOKEN, USA, vol. 56, no. 21, 18 April 2017 (2017-04-18), Hoboken, USA, pages 5817 - 5820, XP072093909, ISSN: 1433-7851, DOI: 10.1002/anie.201702304
FIONN O’HARA, DONNA G. BLACKMOND, PHIL S. BARAN: "Radical-Based Regioselective C–H Functionalization of Electron-Deficient Heteroarenes: Scope, Tunability, and Predictability", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 135, no. 32, 14 August 2013 (2013-08-14), pages 12122 - 12134, XP055675708, ISSN: 0002-7863, DOI: 10.1021/ja406223k
JIANG WU; YANG GU; XUEBING LENG; QILONG SHEN: "Copper‐Promoted Sandmeyer Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, HOBOKEN, USA, vol. 54, no. 26, 12 May 2015 (2015-05-12), Hoboken, USA, pages 7648 - 7652, XP072075412, ISSN: 1433-7851, DOI: 10.1002/anie.201502113
LARSEN MATTHEW A., HARTWIG JOHN F.: "Iridium-Catalyzed C–H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 136, no. 11, 19 March 2014 (2014-03-19), pages 4287 - 4299, XP093048185, ISSN: 0002-7863, DOI: 10.1021/ja412563e
ZHI‐YUN LIU; ZHI‐HUI WEN; XIAO‐CHEN WANG: "B(C6F5)3‐Catalyzed Cascade Reduction of Pyridines", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, HOBOKEN, USA, vol. 56, no. 21, 18 April 2017 (2017-04-18), Hoboken, USA, pages 5817 - 5820, XP072093909, ISSN: 1433-7851, DOI: 10.1002/anie.201702304
Attorney, Agent or Firm:
TIANJIN JUNYAN INTELLECTUAL PROPERTY AGENCY CO., LTD (CN)
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