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CC BY 4.0 · SynOpen 2024; 08(03): 130-137
DOI: 10.1055/s-0043-1775378
paper

Functionalization of Position 7 of Pyrazolo[1,5-a]pyrazines

Georgyi Koidan
a   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar str., 5, Kyiv-94, 02660, Ukraine
,
Nazar Tsyzoryk
a   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar str., 5, Kyiv-94, 02660, Ukraine
,
Eduard B. Rusanov
a   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar str., 5, Kyiv-94, 02660, Ukraine
,
Svitlana V. Shishkina
b   SSI Institute for Single Crystals, Nauki ave. 60, 61001 Kharkiv-01, Ukraine
,
Mykhailo Vovk
a   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar str., 5, Kyiv-94, 02660, Ukraine
,
Aleksandr Kostyuk  ∗
a   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar str., 5, Kyiv-94, 02660, Ukraine
› Author AffiliationsWe gratefully acknowledge the National Research Foundation of Ukraine (No. 2020.02/0105) for financial support.
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Abstract

We report a straightforward formylation at position 7 of pyrazolo[1,5-a]pyrazine derivatives featuring substituents at the 2,3,4 positions. N,N,N′,1,1,1-Hexamethylsilanecarboximidamide exists in equilibrium with its carbene form due to 1,2-migration of the silyl group. The ensuing carbene can be inserted into the most acidic C–H group of the pyrazolo[1,5-a]pyrazines. The most acidic calculated pK a (DMSO) C–H group is at position 7 and does not depend significantly on the substituents. The reactions proceed in high yields affording aminals that can be hydrolyzed to the corresponding aldehydes. Methanolysis of the aminals affords the corresponding methylimines. The constitution of the aminals was unambiguously proved by X-ray crystal structure analysis of a set of derivatives. The method is simple, often does not require even solvents, and can be extended to other heterocyclic compounds.

Key words

pyrazolo[1,5-a]pyrazine - diaminomethylation - aldehyde - carbene - C–H insertion

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1775378.
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Publication History

Received: 18 March 2024

Accepted after revision: 22 May 2024

Article published online:
01 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Abd ul-MalikM. A, Zaki RM, Kamal El-Dean AM, Radwan SM. J. Heterocycl. Chem. 2018; 55: 1828
    Crossref
  • 2 Zheng L.-W, Shao J.-H, Zhao B.-X, Miao J.-Y. Bioorg. Med. Chem. Lett. 2011; 21: 3909
    CrossrefPubMed
  • 3 González SM, Hernández AI, Álvarez RM, Rodríguez A, Ramos-Lima F, Bischoff JR, Albarrán MI, Cebriá A, Hernández-Encinas E, García-Arocha J, Cebrián D, Blanco-Aparicio C, Pastor J. Bioorg. Med. Chem. Lett. 2017; 27: 4794
    CrossrefPubMed
  • 4 Pastor Fernández J, Martínez Gonzáles S, Rodriguéz Hergueta A, Ramos Lima FJ, Alvarez Escobar RM, Higueras Hernández AI. WO 2011/141713, 2011
    PubMed
  • 5 Ninkovic S, Braganza JF, Collins MR, Kath JC, Li H, Richter DT. WO 2010/016005, 2010
    PubMed
  • 6 Gray DL. F, Davoren JE, Dounay AB, Efremov IV, Mente SR, Subramanyam C. WO 2015/166370, 2017
    PubMed
  • 7 Arban R, Bianchi F, Buson A, Cremonesi S, Di Fabio R, Gentile G, Micheli F, Pasquarello A, Pozzan A, Tarsi L, Terreni S, Tonelli F. Bioorg. Med. Chem. Lett. 2010; 20: 5044
    CrossrefPubMed
  • 8 Askew BC, McIntyre CJ, Hunt CA, Claremon DA, Gould RJ, Lynch RJ, Armstrong DJ. Bioorg. Med. Chem. Lett. 1995; 5: 475
    Crossref
  • 9 Woll MG, Qi H, Turpoff A, Zhang N, Zhang X, Chen G, Li C, Huang S, Yang T, Moon Y.-C, Lee C.-S, Choi S, Almstead NG, Naryshkin NA, Dakka A, Narasimhan J, Gabbeta V, Welch E, Zhao X, Risher N, Sheedy J, Weetall M, Karp GM. J. Med. Chem. 2016; 59: 6070
    CrossrefPubMed
  • 10 Liverton N, Kuduk SD, Beshore DC, Meng N, Luo Y. WO 2016/101119, 2016
    PubMed
  • 11 Shen S.-L, Zheng L.-W, Wang S.-Q, Zhang Y.-R, Zhang Y, Liu YR, Zhao B.-X. ARKIVOC 2013; (iv): 44
    Crossref
  • 12 Xie Y.-S, Pan X.-H, Zhao B.-X, Liu J.-T, Shin D.-S, Zhang J.-H, Zheng L.-W, Zhao J, Miao J.-Y. J. Organomet. Chem. 2008; 693: 1367
    Crossref
  • 13 Zhang J.-H, Fan C.-D, Zhao B.-X, Shin D.-S, Dong W.-L, Xie Y.-S, Miao J.-Y. Bioorg. Med. Chem. 2008; 16: 10165
    CrossrefPubMed
  • 14 Pan X.-H, Liu X, Zhao B.-X, Xie Y.-S, Shin D.-S, Zhang S.-L, Zhao J, Miao J.-Y. Bioorg. Med. Chem. 2008; 16: 9093
    CrossrefPubMed
    • 15a Marchenko A, Koidan G, Hurieva A, Shvydenko K, Rozhenko AB, Rusanov EB, Kyrylchuk AA, Kostyuk A. J. Org. Chem. 2022; 87: 373
      CrossrefPubMed
    • 15b Koidan G, Hurieva A, Zahorulko S, Zadorozhny A, Lysenko V, Shvydenko T, Rusanov EB, Kostyuk A. Eur. J. Org. Chem. 2022; 101
    • 15c Koidan G, Zahorulko S, Hurieva A, Shvydenko T, Rusanov EB, Rozhenko AB, Manthe U, Kostyuk A. Chem. Eur. J. 2023; e202301675
      CrossrefPubMed
  • 16 Roszak R, Beker W, Molga K, Grzybowski BA. J. Am. Chem. Soc. 2019; 141 (43) 17142
    CrossrefPubMed
  • 17 Abdul-Malik MA, Zaki RM, El-Dean AM. K, Radwan SM. J. Heterocycl. Chem. 2018; 55: 1828
    Crossref