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Synthesis 2021; 53(24): 4709-4722
DOI: 10.1055/s-0037-1610783
paper

An Expedient Approach to Pyrazolo[3,4-b]pyridine-3-carboxamides via Palladium-Catalyzed Aminocarbonylation

Ryan M. Alam 
a   Analytical & Biological Chemistry Research Facility (ABCRF), University College Cork, Cork T12 YN60, Ireland
b   School of Chemistry, Kane Building, University College Cork, Cork T12 YN60, Ireland
,
John J. Keating  ∗
a   Analytical & Biological Chemistry Research Facility (ABCRF), University College Cork, Cork T12 YN60, Ireland
b   School of Chemistry, Kane Building, University College Cork, Cork T12 YN60, Ireland
c   School of Pharmacy, Pharmacy Building, University College Cork, Cork T12 YN60, Ireland
› Author AffiliationsThis work was supported by funding from Eli Lilly and Company (4152 R17825).
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Abstract

Pyrazolo[3,4-b]pyridine is a privileged scaffold found in many small drug molecules that possess a wide range of pharmacological properties. Efforts to further develop and exploit synthetic methodologies that permit the functionalization of this heterocyclic moiety warrant investigation. To this end, a series of novel 1,3-disubstituted pyrazolo[3,4-b]pyridine-3-carboxamide derivatives have been prepared by introducing the 3-carboxamide moiety using palladium-catalyzed aminocarbonylation methodology and employing CO gas generated ex situ using a two-chamber reactor (COware®). The functional group tolerance of this optimized aminocarbonylation protocol is highlighted through the synthesis of a range of diversely substituted C-3 carbox­amide pyrazolo[3,4-b]pyridines in excellent yields of up to 99%.

Key words

pyrazolo[3,4-b]pyridine - 7-azaindazole - palladium - aminocarbonylation - carboxamide

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610783.
  • Supporting Information


Publication History

Received: 02 June 2021

Accepted after revision: 26 July 2021

Article published online:
26 August 2021

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  • References

  • 1 Zheng W, Wang Z, Jiang X, Zhao Q, Shen J. J. Med. Chem. 2020; 63: 15153
    CrossrefPubMed
  • 2 Smith LM, Ladziata V, Delucca I, Pinto DJ. P, Orwat MJ, Dilger AK, Pabbisetty KB, Yang W, Shaw SA, Glunz PW, Panda M. WO 2017123860A1, 2017
  • 3 Shi J, Xu G, Zhu W, Ye H, Yang S, Luo Y, Han J, Yang J, Li R, Wei Y, Chen L. Bioorg. Med. Chem. Lett. 2010; 20: 4273
    CrossrefPubMed
  • 4 Lin R, Connolly PJ, Lu Y, Chiu G, Li S, Yu Y, Huang S, Li X, Emanuel SL, Middleton SA, Gruninger RH, Adams M, Fuentes-Pesquera AR, Greenberger LM. Bioorg. Med. Chem. Lett. 2007; 17: 4297
    CrossrefPubMed
  • 5 Andoh N, Sanpei O, Toga T, Morris DL, Aston R, Tanaka K, Hino T. World Patent WO2015037747A1, 2016
  • 6 Xing Y, Zuo J, Krogstad P, Jung ME. J. Med. Chem. 2018; 61: 1688
    CrossrefPubMed
  • 7 Collier PN, Twin HC, Knegtel RM. A, Boyall D, Brenchley G, Davis CJ, Keily S, Mak C, Miller A, Pierard F, Settimo L, Bolton CM, Chiu P, Curnock A, Doyle E, Tanner AJ, Jimenez J. ACS Med. Chem. Lett. 2019; 10: 1134
    CrossrefPubMed
  • 8 Panarese JD, Engers DW, Wu Y, Bronson JJ, Macor JE, Chun A, Rodriguez AL, Felts AS, Engers JL, Loch MT, Emmitte KA, Castelhano AL, Kates MJ, Nader MA, Jones CK, Blobaum AL, Conn PJ, Niswender CM, Hopkins CR, Lindsley CW. ACS Med. Chem. Lett. 2019; 10: 255
    CrossrefPubMed
  • 9 Umar T, Shalini S, Raza MK, Gusain S, Kumar J, Seth P, Tiwari M, Hoda N. Eur. J. Med. Chem. 2019; 175: 2
    CrossrefPubMed
  • 10 Moir M, Lane S, Lai F, Connor M, Hibbs DE, Kassiou M. Eur. J. Med. Chem. 2019; 180: 291
    CrossrefPubMed
  • 11 Aronov A, Lauffer DJ, Li P, Tomlinson RC. WO2003078423A1, 2005
  • 12 Lynch BM, Khan MA, Teo HC, Pedrotti F. Can. J. Chem. 1988; 66: 420
    Crossref
  • 13 Mittendorf J, Weigand S, Alonso-Alija C, Bischoff E, Feurer A, Gerisch M, Kern A, Knorr A, Lang D, Muenter K, Radtke M, Schirok H, Schlemmer K, Stahl E, Straub A, Wunder F, Stasch J. ChemMedChem 2009; 4: 853
    CrossrefPubMed
    • 14a Buchler IP, Hayes MJ, Hegde SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK. WO2009106980, 2009
    • 14b Buchler IP, Hayes MJ, Hegde SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK. WO2009106982, 2009
  • 15 Buchstaller H, Wilkinson K, Burek K, Nisar Y. Synthesis 2011; 3089
  • 16 Blaquiere N, Burch J, Castanedo G, Feng JA, Hu B, Staben S, Wu G, Yuen P. WO 2015025025A1, 2015
  • 17 Blake JF, Boyd SA, Cohen F, De Messe J, Fong KC, Gaudino JJ, Kaplan T, Marlow AL, Seo J, Thomas AA, Tian H, Young WB. WO 2007103308, 2007
  • 18 Kannaboina P, Raina G, Kumar KA, Das P. Chem. Commun. 2017; 53: 9446
    CrossrefPubMed
  • 19 Brennführer A, Neumann H, Beller M. Angew. Chem. Int. Ed. 2009; 48: 4114
    CrossrefPubMed
  • 20 Friis SD, Lindhardt AT, Skrydstrup T. Acc. Chem. Res. 2016; 49: 594
    CrossrefPubMed
  • 21 Neumann KT, Lindhardt AT, Bang-Andersen B, Skrydstrup T. Org. Lett. 2015; 17: 2094
    Article in Thieme ConnectPubMed
  • 22 Bhilare S, Shah J, Gaikwad V, Gupta G, Sanghvi YS, Bhanage BM, Kapdi AR. Synthesis 2019; 51: 4239
    CrossrefPubMed
  • 23 Gockel SN, Hull KL. Org. Lett. 2015; 17: 3236
    CrossrefPubMed
  • 24 Wan Y, Alterman M, Larhed M, Hallberg A. J. Org. Chem. 2002; 67: 6232
    CrossrefPubMed
  • 25 Kaiser NK, Hallberg A, Larhed M. J. Comb. Chem. 2002; 4: 109
    Article in Thieme ConnectPubMed
  • 26 Mamone M, Aziz J, Le Bescont J, Piguel S. Synthesis 2018; 50: 1521
    Article in Thieme Connect
  • 27 Babjak M, Caletková O, Ďurišová D, Gracza T. Synlett 2014; 25: 2579
    CrossrefPubMed
  • 28 Friis SD, Taaning RH, Lindhardt AT, Skrydstrup T. J. Am. Chem. Soc. 2011; 133: 18114
    CrossrefPubMed
  • 29 Hermange P, Lindhardt AT, Taaning RH, Bjerglund K, Lupp D, Skrydstrup T. J. Am. Chem. Soc. 2011; 133: 6061
    Article in Thieme ConnectPubMed
  • 30 Flinker M, Lopez S, Nielsen DU, Daasbjerg K, Jensen F, Skrydstrup T. Synlett 2017; 28: 2439
    Crossref
  • 31 Yin Z, Wu X. Org. Process Res. Dev. 2017; 21: 1869
    CrossrefPubMed
  • 32 Markovič M, Lopatka P, Koóš P, Gracza T. Org. Lett. 2015; 17: 5618
    CrossrefPubMed
  • 33 Veryser C, Van Mileghem S, Egle B, Gilles P, De Borggraeve WM. React. Chem. Eng. 2016; 1: 142
    Crossref
  • 34 Peng J, Geng H, Wu X. Chem 2019; 5: 526
  • 35 Barnard CF. J. Organometallics 2008; 27: 5402
    Article in Thieme Connect
  • 36 Fang W, Zhu H, Deng Q, Liu S, Liu X, Shen Y, Tu T. Synthesis 2014; 46: 1689
    CrossrefPubMed
  • 37 Jian X, Yang F, Jiang C, You W, Zhao P. Bioorg. Med. Chem. Lett. 2020; 30: 127025
    CrossrefPubMed
  • 38 Dierkes P, Van Leeuwen PW. N. M. J. Chem. Soc., Dalton Trans. 1999; 1519
    CrossrefPubMed
  • 39 Martinelli JR, Watson DA, Freckmann DM. M, Barder TE, Buchwald SL. J. Org. Chem. 2008; 73: 7102
    CrossrefPubMed
  • 40 Van der Veen LA, Keeven PH, Schoemaker GC, Reek JN. H, Kamer PC. J, Van Leeuwen PW. N. M, Lutz M, Spek AL. Organometallics 2000; 19: 872
    CrossrefPubMed
  • 41 Jover J, Cirera J. Dalton Trans. 2019; 15036
    CrossrefPubMed
  • 42 Doherty S, Knight JG, Ward NA. B, Bittner DM, Wills C, McFarlane W, Clegg W, Harrington RW. Organometallics 2013; 32: 1773
    Crossref
  • 43 Roy S, Roy S, Gribble GW. Tetrahedron 2012; 68: 9867
    Crossref
  • 44 Beller M, Wu X. A Discussion Between Carbonylation, Noncarbonylation and Decarbonylation. Transition Metal Catalyzed Carbonylation Reactions: Carbonylative Activation of C-X Bonds. Springer-Verlag; Berlin: 2013: 215-221
    CrossrefGoogle Scholar
  • 45 Langueux-Tremblay P, Fabrikant A, Arndtsen BA. ACS Catal. 2018; 8: 5350
    CrossrefPubMed
  • 46 Nielsen DU, Taaning RH, Lindhardt AT, Gøgsig TM, Skrydstrup T. Org. Lett. 2011; 13: 4454
    CrossrefPubMed
  • 47 Ismael A, Gevorgyan A, Skrydstrup T, Bayer A. Org. Process Res. Dev. 2020; 24: 2665
    CrossrefPubMed
  • 48 Wannberg J, Larhed M. J. Org. Chem. 2003; 68: 5750
    CrossrefPubMed
  • 49 Åkerbladh L, Schembri LS, Larhed M, Odell LR. J. Org. Chem. 2017; 82: 12520
    CrossrefPubMed
  • 50 Boyarskii VP. Russ. J. Gen. Chem. 2008; 78: 1511
    Crossref
  • 51 Gabriele B, Salerno G, Veltri L, Costa M. J. Organomet. Chem. 2001; 622: 84
    Crossref
  • 52 Dong Y, Sun S, Yang F, Zhu Y, Zhu W, Qiao H, Wu Y, Wu Y. Org. Chem. Front. 2016; 3: 720
    CrossrefPubMed
  • 53 Hughes NL, Brown CL, Irwin AA, Cao Q, Muldoon MJ. ChemSusChem 2017; 10: 675
    CrossrefPubMed
  • 54 Ran L, Ren Z, Wang Y, Guan Z. Chem. Asian J. 2014; 9: 577
    CrossrefPubMed
  • 55 Das D, Bhanage BM. Adv. Synth. Catal. 2020; 362: 3022
    Crossref