Journal of Chemical Sciences

, Volume 129, Issue 10, pp 1579–1586 | Cite as

Synthesis of 7-arylethyl-5-arylpyrazolo\([1{,}5\hbox {-}a]\)pyrimidines through an aza-Michael addition/nucleophilic addition/1,3-hydrogen transfer cascade

  • Zheng Li
  • Demeng Xie
  • Jiaojiao He
  • Yan Du
  • Jingya Yang
Regular Article


An efficient method for the synthesis of pyrazolo\([1{,}5\hbox {-}a]\)pyrimidines by the tandem reactions of dienones with pyrazole-3-amine through an aza-Michael addition/nucleophilic addition/1,3-hydrogen transfer process in the presence of potassium hydroxide is described. This protocol offers access to 7-arylethyl-5-arylpyrazolo\([1{,}5\hbox {-}a]\)pyrimidines in good to excellent yield. Meanwhile for 4-substituted dienones, different products, 7-arylethylene-5-arylpyrazolo\([1{,}5\hbox {-}a]\)pyrimidines, are given through an aza-Michael addition/nucleophilic addition/oxidation process. A gram-scale reaction has been performed to demonstrate the potency of optimized procedure for the scale-up process.

Graphical Abstract

SYNOPSIS7-Arylethyl-5-arylpyrazolo\([1{,}5\hbox {-}a]\)pyrimidines were efficiently synthesized by the reactions of 4-unsubstituted dienones with pyrazole-3-amine. In contrast, 7-arylethylene-5-arylpyrazolo\([1{,}5\hbox {-}a]\)pyrimidines could be afforded by the reactions of 4-substituted dienones with pyrazole-3-amine.


Pyrazole-3-amine dienone pyrazolo[1, 5-a]pyrimidine tandem reaction heterocyclization 



The authors thank the National Natural Science Foundation of China (21462038, 21362034) and Key Laboratory of Eco-Environment-Related Polymer Materials of Ministry of Education for the financial support of this work.

Supplementary material

12039_2017_1365_MOESM1_ESM.docx (9 mb)
Supplementary material 1 (docx 9175 KB)


  1. 1.
    Ivachtchenko A V, Golovina E S, Kadieva M G, Kysil V M, Mitkin O D, Tkachenko S E and Okun I M 2011 Synthesis and structure-activity relationship (SAR) of (5,7-disubstituted 3-phenylsulfonyl-pyrazolo[1,5\(\text{-}a\)) antagonists J. Med. Chem. 54 8161Google Scholar
  2. 2.
    Damont A, Medran-Navarrete V, Cacheux F, Kuhnast B, Pottier G, Bernards N, Marguet F, Puech F, Boisgard R and Dolle F 2015 Novel pyrazolo\([1,5\text{- }a]\)]-labeling, and in Vivo neuroinflammation PET images J. Med. Chem.  58 7449CrossRefGoogle Scholar
  3. 3.
    Sanna E, Busonero F, Talani G, Carta M, Massa F, Peis M, Maciocco E and Biggio G 2002 Comparison of the effects of zaleplon, zolpidem, and triazolam at various \(\text{ GABA }_{{\rm A}}\) receptor subtypes Eur. J. Pharmacol. 451 103CrossRefGoogle Scholar
  4. 4.
    Martin M P, Olesen S H, Georg G I and Schonbrunn E 2013 Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains ACS Chem. Biol. 8 2360CrossRefGoogle Scholar
  5. 5.
    Castillo-Sanchez J, Aguilera-del Real A, Rodriguez-Sanchez M and Valverde-Garcia A 2000 Residue levels, decline curves, and plantation distribution of procymidone in green beans grown in greenhouse J. Agric. Food Chem. 48 2991CrossRefGoogle Scholar
  6. 6.
    Walsh J K, Moscovitch A, Burke J, Farber R and Roth T 2007 Efficacy and tolerability of indiplon in older adults with primary insomnia Sleep Med. 8 753CrossRefGoogle Scholar
  7. 7.
    Vinkers C H, Olivier B, Hanania T, Min W, Schreiber R, Hopkins S C, Campbell U and Paterson N 2011 Discriminative stimulus properties of \(\text{ GABA }_{\rm A}\) receptor positive allosteric modulators TPA023, ocinaplon and NG2-73 in rats trained to discriminate chlordiazepoxide or zolpidem Eur. J. Pharmacol. 668 190CrossRefGoogle Scholar
  8. 8.
    Tsai P C and Wang I J 2007 A facile synthesis of some new pyrazolo[1,5-\(a\)]pyrimidine heterocyclic disazo dyes and an evaluation of their solvatochromic behaviour Dyes Pigm. 74 578CrossRefGoogle Scholar
  9. 9.
    Tsai P C and Wang I J 2008 Synthesis and solvatochromic properties of 3,6-bis-hetarylazo dyes derived from pyrazolo[1,5\(\text{- }a\)]pyrimidine Dyes Pigm. 76 575Google Scholar
  10. 10.
    Tsai P C and Wang I J 2005 Synthesis and solvatochromic properties of some disazo dyes derived from pyrazolo[1,5\(\text{- }a\)]pyrimidine derivatives Dyes Pigm. 64 259Google Scholar
  11. 11.
    Sayed A Z, Aboul-Fetouh M S and Nassar H S 2012 Synthesis, biological activity and dyeing performance of some novel azo disperse dyes incorporating pyrazolo[1,5\(\text{- }a\)]pyrimidines for dyeing of polyester fabrics J. Mol. Struct. 1010 146CrossRefGoogle Scholar
  12. 12.
    Alcaide B, Almendros P and Quiros M T 2014 Gold/acid-co-catalyzed direct microwave-assisted synthesis of fused azaheterocycles from propargylic hydroperoxides Chem. Eur. J. 20 3384CrossRefGoogle Scholar
  13. 13.
    Saikia P, Gogoi S and Boruah R C 2015 Carbon-carbon bond cleavage reaction: Synthesis of multisubstituted pyrazolo[1,5\(\text{- }a\)]pyrimidines J. Org. Chem. 80 6885Google Scholar
  14. 14.
    Kaswan P, Pericherla K, Purohit D and Kumar A 2015 Synthesis of 5,7-diarylpyrazolo[1,5\(\text{- }a\)-pyrazol-3-amines and chalcones Tetrahedron Lett. 56 549Google Scholar
  15. 15.
    Zhang X, Song Y, Gao L, Guo X and Fan X 2014 Highly facile and regio-selective synthesis of pyrazolo[1,5\(\text{- }a\)]pyrimidines via reactions of 1,2-allenic ketones with aminopyrazoles Org. Biomol. Chem. 12 2099Google Scholar
  16. 16.
    Yin L and Liebscher J 2004 Convenient synthesis of substituted 3-alkenylpyrazolo[1,5\(\text{- }a\)]pyrimidines via Heck cross-coupling reaction Synthesis 2329Google Scholar
  17. 17.
    Mokhtar M, Saleh T S and Basahel S N 2012 Mg-Al hydrotalcites as efficient catalysts for aza-Michael addition reaction: A green protocol J. Mol. Catal. A: Chem. 353–354 122CrossRefGoogle Scholar
  18. 18.
    Bassoude I, Berteina-Raboin S, Leger J M, Jarry C, Essassi E M and Guillaumet G 2011 One-step reaction leading to new pyrazolo\([1,5\text{- }a]\)pyrimidines by condensation of 2-pyrone with 5(3)-amino-3(5)-arylpyrazoles Tetrahedron 67 2279CrossRefGoogle Scholar
  19. 19.
    Xin Y, Zang Z H and Chen F L 2009 Ultrasound-promoted synthesis of 1,5-diarylpenta-2,4-dien-1-ones catalyzed by activated barium hydroxide Synth. Commun. 39 4062CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  • Zheng Li
    • 1
  • Demeng Xie
    • 1
  • Jiaojiao He
    • 1
  • Yan Du
    • 1
  • Jingya Yang
    • 1
  1. 1.College of Chemistry and Chemical EngineeringNorthwest Normal UniversityLanzhouPeople’s Republic of China

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