Synthesis 2016; 48(14): 2201-2204
DOI: 10.1055/s-0035-1562230
psp
© Georg Thieme Verlag Stuttgart · New York

A Multicomponent Approach to Highly Substituted 1H-Pyrazolo[3,4-b]pyridines

Matthew D. Hill*
Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA   eMail: matthew.hill@bms.com
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 29. Februar 2016

Accepted after revision: 28. April 2016

Publikationsdatum:
17. Mai 2016 (online)


Abstract

Multicomponent reactions make up an important subclass of azaheterocycle syntheses. In this report, a mild and catalyst-free multicomponent preparation of 1H-pyrazolo[3,4-b]pyridines is described. This one-pot synthesis uses simple aldehyde, 3-oxopropanenitrile, and 1H-pyrazol-5-amine starting materials to rapidly access structurally diverse products. Additionally, the impact of 1H-pyrazol-5-amine C3 substituents on the formation of 1H-pyrazolo[3,4-b]pyridines vs pyrazolo[1,5-a]pyrimidine structural isomers is discussed.

Supporting Information

 
  • References

  • 1 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
  • 2 Heterocycles in Natural Product Synthesis . Majumdar KC, Chattopadhyay SK. Wiley-VCH; Weinheim: 2011
    • 3a Joule JA, Mills K. Heterocyclic Chemistry . 5th ed Wiley-Blackwell; New York: 2010
    • 3b Kumari S, Kishore D, Paliwal S, Chauhan R, Dwivedi J, Mishra A. Mol. Divers. 2016; 20: 185

      For reviews, see:
    • 5a Gulevich AV, Dudnik AS, Chernyak N, Gevorgyan V. Chem. Rev. 2013; 113: 3084
    • 5b Chinchilla R, Nájera C, Yus M. Chem. Rev. 2004; 104: 2667
    • 5c Turck A, Plé N, Mongin F, Quéguiner G. Tetrahedron 2001; 57: 4489
    • 6a Stein RG, Biel JH, Singh T. J. Med. Chem. 1970; 13: 153
    • 6b Gatta F, Pomponi M, Marta M. J. Heterocycl. Chem. 1991; 28: 1301
    • 6c Misra RN, Rawlins DB, Xiao H, Shan W, Bursuker I, Kellar KA, Mulheron JG, Sack JS, Tokarski JS, Kimball SD, Webster KR. Bioorg. Med. Chem. Lett. 2003; 13: 1133
    • 6d Straub A, Buckholz J, Fröde R, Kern A, Kohlsdorfer C, Schmitt P, Schwarz T, Siefert H, Stasch J. Bioorg. Med. Chem. 2002; 10: 1711
    • 6e Quiroga J, Portilla J, Insuasty B, Abnia R, Nogueras M, Sortino M, Zacchino S. J. Heterocycl. Chem. 2005; 42: 61
    • 6f Wenglowsky S, Ahrendt KA, Buckmelter AJ, Feng B, Gloor SL, Gradi S, Gradi J, Hansen JD, Laird ER, Lunghofer P, Mathieu S, Moreno D, Newhouse B, Ren L, Risom T, Rudolph J, Seo J, Sturgis HL, Voeglti WC, Wen Z. Bioorg. Med. Chem. Lett. 2011; 21: 5533

      Alternatives to this method require extreme temperatures (180 °C), 1-phenyl-1H-pyrazol-5-amine starting materials, and/or isolation of 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine intermediates, see:
    • 7a Rahmati A, Khalesi Z. Chin. Chem. Lett. 2012; 23: 1149
    • 7b Zhu S.-L, Ji S.-J, Zhao K, Liu Y. Tetrahedron Lett. 2008; 49: 2578
    • 7c El-borai MA, Rizk HF, Abd-AaI MF, El-Deeb IY. Eur. J. Med. Chem. 2012; 48: 92
    • 7d Huang Z, Hu Y, Zhou Y, Shi D. ACS Comb. Sci. 2011; 13: 45
    • 7e Bedjeguelal K, Rabot R, Kaloun EB, Mayer P, Marchand A, Rahier N, Schambel P, Bienayme H. WO 2011045344, 2011
  • 8 See supplemental materials for characterization data.
  • 9 Knoevenagel E. Ber. Dtsch. Chem. Ges. 1898; 31: 2596
  • 10 Winters G, Sala A, De Paoli A, Conti M. Synthesis 1984; 1050
  • 11 Regiochemical outcome was confirmed by single-crystal X-ray analysis.
  • 12 Li P, Fang F, Chen J, Wang J. Tetrahedron: Asymmetry 2014; 25: 98
  • 13 Brigance RP, Meng W, Fura A, Harrity T, Wang A, Zahler R, Kirby MS, Hamann LG. Bioorg. Med. Chem. Lett. 2010; 20: 4395
  • 14 Allen CF. H, Wolf CN. Org. Synth. Coll. Vol. IV. John Wiley & Sons; London: 1963: 45