Download PDF
Synlett 2020; 31(13): 1277-1281
DOI: 10.1055/s-0040-1707138
letter
© Georg Thieme Verlag Stuttgart · New York

Site-Selective Suzuki–Miyaura Reaction of 6,8-Dichloro-1,2,4-triazolo[4,3-a]pyridines

David Kuhrt
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b   Leibniz Institut für Katalyse, Albert-Einstein-Str. 29a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Ehlers
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b   Leibniz Institut für Katalyse, Albert-Einstein-Str. 29a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Anke Spannenberg
b   Leibniz Institut für Katalyse, Albert-Einstein-Str. 29a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Langer∗
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b   Leibniz Institut für Katalyse, Albert-Einstein-Str. 29a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
› Author AffiliationsFinancial support by the federal state of Mecklenburg-Vorpommern is gratefully acknowledged.
Further Information

Publication History

Received: 09 April 2020

Accepted after revision: 10 May 2020

Publication Date:
03 June 2020 (online)

    Permissions and Reprints All articles of this category


Abstract

Triazolopyridines have found various applications as pharmaceuticals, agrochemicals, or optical materials. Consequently, the introduction of various functionalities at specific sites of this heterocyclic framework is of great importance. In this regard, we report the development of a site-selective Suzuki–Miyaura reactions leading to substituted triazolopyridines at positions 6 and 8. Under optimized conditions, the respective products have been obtained with high selectivity and yield.

Key words

triazolopyridines - regioselectivity - aryl chlorides - palladium catalysis - Suzuki–Miyaura reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707138.
  • Supporting Information
 

  • References and Notes

  • 4 Liu X.-H, Xu X.-Y, Tan C.-X, Wenig J.-Q, Xin J.-H, Chen J. Pest Manag. Sci. 2015; 71: 292
    CrossrefPubMedSearch in Google Scholar
    • 6a Jaśkowska J, Zaręba P, Śliwa P, Pindelska E, Satała G, Majka Z. Molecules 2019; 24: 1609
      CrossrefPubMedSearch in Google Scholar
    • 6b Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, Ye SP, O’Connor X.-Y, Chen S, Wu S, Yoon DS, Nayeem A, Camac DM, Ramamurthy V, Morin PE, Sheriff S, Wang M, Harper TW, Golla R, Seethala R, Harrity T, Ponticiello RP, Morgan NN, Taylor JR, Zebo R, Maxwell B, Moulin F, Gordon JA, Robl DA. ACS Med. Chem. Lett. 2018; 9: 1170
      CrossrefPubMedSearch in Google Scholar
    • 6c Wurtz NR, Viet A, Shaw SA, Dilger A, Valente MN, Khan JA, Jusuf S, Narayanan R, Fernando G, Lo F, Liu X, Locke GA, Kopcho L, Abell LM, Sleph P, Basso M, Zhao L, Wexler RR, Duclos F, Kick EK. ACS Med. Chem. Lett. 2018; 9: 1175
      CrossrefPubMedSearch in Google Scholar
    • 6d Bonafoux D, Nanthakumar S, Bandarage UK, Memmott C, Lowe D, Aronov AM, Bhisetti GR, Bonanno KC, Coll J, Leeman J, Lepre CA, Lu F, Perola E, Rijnbrand R, Taylor WP, Wilson D, Zhou Y, Zwahlen J, ter Haar E. J. Med. Chem. 2016; 59: 7138
      CrossrefPubMedSearch in Google Scholar
    • 6e Menet CJ, Fletcher SR, Van Lommen G, Geney R, Blanc J, Smits K, Jouannigot N, Deprez P, van der Aar E, Clement-Lacroix P, Lepescheux L, Galien R, Vayssiere B, Nelles L, Christophe T, Brys R, Uhrig M, Ciesielski F, Van Rompaey L. J. Med. Chem. 2014; 57: 9323
      CrossrefPubMedSearch in Google Scholar
    • 6f Peterson EA, Teffera Y, Albrecht BK, Bauer D, Bellon SF, Boezio A, Boezio C, Broome MA, Choquette D, Copeland KW, Dussalt I, Lewis R, Lin M.-HJ, Lohman J, Liu J, Potashman M, Rex K, Shimanovich R, Whittington DA, Vaida KR, Harmange J.-C. J. Med. Chem. 2015; 58: 2417
      CrossrefPubMedSearch in Google Scholar
    • 6g Jemaà M, Galluzzi L, Kepp O, Senovilla L, Brands M, Boemer U, Koppitz M, Lienau P, Prechtl S, Schulze V, Siemeister G, Wengner AM, Mumberg D, Ziegelbauer K, Abrieu A, Castedo M, Vitale I, Kroemer G. Cell Death Differ. 2013; 20: 1532
      CrossrefPubMedSearch in Google Scholar
    • 6h Cid JM, Tresdern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML, Garcia A, Andrés JI, Macdonald GJ, Oehlrich D, Lavreyessen H, Megens A, Ahnaou A, Drinkenburg W, Mackie C, Pryde S, Gallacher D, Trabanco AA. J. Med. Chem. 2012; 55: 8770
      CrossrefPubMedSearch in Google Scholar
    • 6i Sadana AK, Mirza Y, Aneja KR, Prakash O. Eur. J. Med. Chem. 2003; 38: 533
      CrossrefPubMedSearch in Google Scholar
  • 8 CCDC 1976133–1976136 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
    • 10a Triazolopyridines 3a–m; General Procedure Triazolopyridine 1 or 2 (0.57 mmol, 150 mg), the appropriate boronic acid (1.31 mmol, 2.3 equiv), K3PO4 (2.27 mmol, 482 mg, 4.0 equiv), Pd(OAc)2 (0.03 mmol, 6.3 mg, 5 mol%), and SPhos ligand (0.06 mmol, 23.0 mg, 10 mol%) were added to an argon-flushed glass pressure tube. Toluene (5 mL) was added, and the mixture was heated to 100 °C for 24 h, then cooled. The solvent was evaporated, and the crude product was purified by column chromatography (silica gel, heptane–EtOAc). 3,6,8-Triphenyl[1,2,4]triazolo[4,3-a]pyridine (3a) White solid; yield: 189 mg (96%); mp 206–207 °C. IR (ATR): 3367 (w), 3075 (w), 2965 (w), 2922 (w), 2864 (w), 1478 (m), 1446 (w), 1359 (w), 1265 (w), 1076 (w), 888 (w), 839 (w), 764 (s), 695 (s), 591 (m), 512 (m), 449 (w) cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.36 (d, J = 1.5 Hz, 1 H), 8.23–8.16 (m, 2 H), 7.93–7.86 (m, 2 H), 7.70 (d, J = 1.5 Hz, 1 H), 7.66–7.41 (m, 11 H). 13C NMR (75 MHz, CDCl3): δ = 118.22 (CH), 126.23 (CH), 126.84 (C), 127.29 (2 CH), 128.73, 128.92, 129.03, 129.39 (CH), 129.41, 129.47, 129.53, 129.91, 130.45 (CH), 134.84, 136.61, 147.59, 149.11. MS (EI): m/z (%) = 347 [M + ] (100), 244 (20), 216 (18), 189 (12), 165 (3), 140 (4), 103 (7), 77 (5). HRMS (EI): m/z [M]+ calcd for C24H17N3: 347.14170; found: 347.14106.