Synthesis of tetracyclic pyrido-fused dibenzodiazepines via a catalyst-free cascade reaction

Abstract

An efficient, eco-friendly protocol has been described for the chemoselective synthesis of tetracyclic pyrido-fused dibenzodiazepines derivatives via catalyst-free, three-component reaction of dimedone, 1,2-diamines, 3-formylchromones, and malononitrile. The significant advantages of this cascade approach are to create two new rings and four new σ bonds containing three C–N and one C–C bond, as well as the breakdown of a C–O bond.

Graphic Abstract

This is a preview of subscription content, log in to check access.

Fig. 1
Scheme 1
Fig. 2
Scheme 2

References

  1. 1.

    McGowan D, Nyanguile O, Cummings MD, Vendeville S, Vandyck K, Van den Broeck W, Boutton CW, De Bondt QLH, Amssoms K, Bonfanti JF, Last S, Rombauts K, Tahri A, Hu L, Delouvroy F, Vermeiren K, Vandercruyssen G, Van der Helm L, Cleiren E, Mostmans W, Lory P, Pille G, Van Emelen K, Fanning G, Pauwels F, Lin TI, Simmen K, Raboisson P (2009) 1,5-benzodiazepine inhibitors of HCV NS5B polymerase. Bioorg Med Chem Lett 19:2492. https://doi.org/10.1016/j.bmcl.2009.03.035

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Schimer J, Cigler P, Vesely J, Grantz-Saskova K, Lepsik M, Brynda J, Rezacova P, Kozisek M, Cisarova I, Oberwinkler H, Kraeusslich HG, Konvalinka J (2012) Structure-aided design of novel inhibitors of HIV protease based on a benzodiazepine scaffold. J Med Chem 55:10130. https://doi.org/10.1021/jm301249q

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Raboisson PJMB, Vendeville SMH, Bonfanti JF, McGowan D, Vandyck K, Doublet FMM, Hu LL, Nyanguile O (2008) 10-sulfonyl-dibenzodiazepinones useful as hepatitis c virus inhibitors. PCT Int Appl WO 2008099022A1 20080821

  4. 4.

    Charre D, Blehaut H, Bellamy F (2013) Inhibitors of cystathionine beta-synthase to reduce the neurotoxic overproduction of endogenous hydrogen sulfide. PCT Int Appl WO 2013068592A1 20130516

  5. 5.

    Fu JS, Shuttleworth SJ, Connors RV, Chai A, Coward P (2009) Discovery and optimization of a novel neuromedin B receptor antagonist. Bioorg Med Chem Lett 19:4264. https://doi.org/10.1016/j.bmcl.2009.05.124

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Insuasty B, Ramrez J, Becerra D, Echeverry C, Quiroga J, Abonia R, Robledo SM, Velez ID, Upegui Y, Munoz JA, Ospina V, Nogueras M, Cobo J (2015) An efficient synthesis of new caffeine-based chalcones, pyrazoline and pyrazolo[3,4-b][1,4]diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents. Eur J Med Chem 93:401. https://doi.org/10.1016/j.ejmech.2015.02.040

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Insuasty B, Orozco F, Quiroga J, Abonia R, Nogueras M, Cobo J (2008) Microwave induced synthesis of novel 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor agents. Eur J Med Chem 43:1955. https://doi.org/10.1016/j.ejmech.2007.12.005

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Carabateas PM, Harris LS (1966) Analgesic antagonists. I. 4-substituted 1-acyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepines. J. Med. Chem. 9:6. https://doi.org/10.1021/jm00319a002

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Tonkikh NN, Strakovs A, Rizhanova KV, Petrova MV (2004) 11-Aryl-3,3-dimethyl-7- and 7,8-substituted 1,2,3,4,10,11-hexahydro-5H-dibenzo[b, e]-1,4-diazepin-1-ones. Chem Heterocycl Compd 40:949. https://doi.org/10.1023/B:COHC.0000044581.23486.59

    CAS  Article  Google Scholar 

  10. 10.

    Dourlat J, Liu WQ, Gresh N, Garbay C (2007) Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines. Bioorg Med Chem Lett 17:2527. https://doi.org/10.1016/j.bmcl.2007.02.016

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Organon NV (2008) Pyridooxazepine progesterone receptor modulators. US2008/90804, A1

  12. 12.

    Akzo Nobel NV (2006) Non-steroidal glucocorticoid receptor modulators. WO2006/84917, A1

  13. 13.

    Nathwani SM, Greene LM, Butini S, Campiani G, Williams DC, Samali A, Szegezdi E, Zisterer DM (2016) The pyrrolo-1,5-benzoxazepine, PBOX-15, enhances TRAIL-induced apoptosis by upregulation of DR5 and downregulation of core cell survival proteins in acute lymphoblastic leukemia cells. Int J Oncol 49:74. https://doi.org/10.3892/ijo.2016.3518

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Parmar NJ, Barad HA, Pansuriya BR, Teraiya ShB, Gupta VK, Kant R (2012) An efficient one-pot synthesis, structure, antimicrobial and antioxidant investigations of some novel quinolyldibenzo[b, e][1,4]diazepinones. Bioorg Med Chem Lett 22:3816. https://doi.org/10.1016/j.bmcl.2012.03.100

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Cherfaoui B, Lakhdari H, Bennamane N, Ameraoui R, Talhi O, Almeida Paz FA, Bachari Kh, Kirsch G, Nejar-Bellara K, Silva AMS (2017) Dibenzo[b, e][1,4]diazepin-1-ones and their ring-opened derivatives: revisited synthesis, 2D NMR and crystal structure. Synlett 28:2247. https://doi.org/10.1055/s-0036-1590306

    CAS  Article  Google Scholar 

  16. 16.

    Jiang B, Li QY, Zhang H, Tu ShJ, Pindi S, Li G (2012) Efficient domino approaches to multi functionalized fused pyrroles and dibenzo[b, e][1,4]diazepin-1-ones. Org Lett 14:700. https://doi.org/10.1021/ol203166c

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Orlova ZI, Ukhin LY, Suponitskii KY, Shepelenko EN, Belousova LV, Borodkin GS, Popovaa OS (2013) Synthesis, structure, and properties of new spirooxindolodibenzodiazepine derivatives. Russ Chem Bull Int Ed 62:1409. https://doi.org/10.1007/s11172-013-0203-1

    CAS  Article  Google Scholar 

  18. 18.

    Tolpygin IE, Mikhailenko NV, Bumber AA, Shepelenko EN, Revinsky UV, Dubonosov AD, Bren VA, Minkin VI (2012) 11-R-dibenzo[b, e][1,4]diazepin-1-ones, the chemosensors for transition metal cations. Russ J Org Chem 82:1243. https://doi.org/10.1134/S1070363212070109

    CAS  Article  Google Scholar 

  19. 19.

    Nasir Z, Ali A, Shakir M, Wahab R, Lutfullah Sh (2017) Silica-supported NiO nanocomposites prepared via a sol-gel technique and their excellent catalytic performance for the one-pot multi-component synthesis of benzodiazepine derivatives under microwave irradiation. New J Chem 41:5893. https://doi.org/10.1039/C6NJ04013F

    CAS  Article  Google Scholar 

  20. 20.

    De K, Bhanja P, Bhaumik A, Mukhopadhyay Ch (2017) Zeolite-Y-mediated multicomponent reaction of isatins, cyclic 1,3-diketones, and 1,2-phenylenediamine: easy access to spirodibenzo[1,4]diazepines. Chem Cat Chem 10:590. https://doi.org/10.1002/cctc.201701487

    CAS  Article  Google Scholar 

  21. 21.

    Moeini Korbekandi M, Nasr-Esfahani M, Mohammadpoor-Baltork I, Moghadam M, Tangestaninejad S, Mirkhani V (2019) Preparation and application of a new supported nicotine-based organocatalyst for the synthesis of various 1,5-benzodiazepines. Catal Lett 149:1057. https://doi.org/10.1007/s10562-019-02668-z

    CAS  Article  Google Scholar 

  22. 22.

    Wang Y, Shi F, Yao XX, Sun M, Dong L, Tu Sh (2014) Catalytic asymmetric construction of 3,3′-spirooxindoles fused with seven-membered rings by enantioselective tandem reactions. J Chem Eur J 20:1. https://doi.org/10.1002/chem.201403868

    CAS  Article  Google Scholar 

  23. 23.

    Wang Y, Tu MS, Shi F, Tu Sh (2014) Enantioselective construction of the biologically significant dibenzo[1,4]diazepine scaffold via organocatalytic asymmetric three-component reactions. J Adv Synth Catal 356:2009. https://doi.org/10.1002/adsc.201400095

    CAS  Article  Google Scholar 

  24. 24.

    Wang ShL, Cheng Ch, Wu FY, Li J, Jiang B, Tu Sh (2011) An efficient three-component tandem reaction leading to pentacyclic isoindole-fused benzo[b, e][1,4]diazepines in Water. J Chem Lett 40:834. https://doi.org/10.1246/cl.2011.834

    CAS  Article  Google Scholar 

  25. 25.

    Shaabani A, Hooshmand SE, Nazeri MT, Afshari R, Ghasemi Sh (2016) Deep eutectic solvent as a highly efficient reaction media for the one-pot synthesis of benzo-fused seven-membered heterocycles. Tetrahedron Lett 57:3727. https://doi.org/10.1016/j.tetlet.2016.07.005

    CAS  Article  Google Scholar 

  26. 26.

    Kausar N, Mukherjee P, Das RA (2016) Practical carbocatalysis by graphene oxide nanosheets in aqueous medium towards the synthesis of diversified dibenzo[1,4]diazepine scaffolds. RSC Adv 6:88904. https://doi.org/10.1039/C6RA17520A

    CAS  Article  Google Scholar 

  27. 27.

    Alizadeh A, Bagherinejad A (2020) A catalyst-free synthetic route to modified isoflavone via multi-component reaction. ChemistrySelect 5:1547. https://doi.org/10.1002/slct.201904674

    CAS  Article  Google Scholar 

  28. 28.

    Alizadeh A, Rezvanian A, Zhu LG (2012) Synthesis of heterocyclic [3.3.3]propellanes via a sequential four-component reaction. J Org Chem 77:4385. https://doi.org/10.1021/jo300457m

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Alizadeh A, Bayat F, Moafi L, Zhu LG (2015) 5-Hydroxybenzo[g]indoles formation from oxa-aza[3.3.3]propellanes. Tetrahedron 71:8150. https://doi.org/10.1016/j.tet.2015.08.035

    CAS  Article  Google Scholar 

  30. 30.

    Alizadeh A, Ghanbaripour R, Zhu LG (2014) Piperidine-iodine a dual system catalyst for synthesis of coumarin bearing pyrrolo[1,2-a]quinoxaline derivatives via a one-pot three-component reaction. Tetrahedron 70:2048. https://doi.org/10.1016/j.tet.2014.01.038

    CAS  Article  Google Scholar 

  31. 31.

    Alizadeh A, Rezvanian A (2012) Powerful approach to synthesis of fused oxa-aza[3.3.3]propellanes via chemoselective sequential MCR in a single pot. Tetrahedron 68:10164. https://doi.org/10.1016/j.tet.2012.09.101

    CAS  Article  Google Scholar 

  32. 32.

    Alizadeh A, Basiri S, Bayat F, Halvagar MR, Zhu LG (2017) Application of oxa-aza[3.3.3]propellanes in the diastereoselective synthesis of indeno[1,2-b]pyrroles bearing bistriazole unit. Tetrahedron 73:5800. https://doi.org/10.1016/j.tet.2017.08.029

    CAS  Article  Google Scholar 

  33. 33.

    Alizadeh A, Rezvanian A, Zhu LG (2012) Chemo- and regioselective 4CR synthesis of oxathiaaza[3.3.3]propellanes via sequential C–S, C–N and C–O bond formation in a single pot. Synlett 23:2526. https://doi.org/10.1021/jo300457m

    CAS  Article  Google Scholar 

  34. 34.

    Alizadeh A, Bayat F, Zhu LG (2014) Regioselective multicomponent sequential synthesis of oxa-aza[3.3.3]propellanes. Aust J Chem 67:949. https://doi.org/10.1071/CH13654

    CAS  Article  Google Scholar 

  35. 35.

    Adib M, Zainali M, Kim I (2016) An efficient three-component synthesis of benzimidazo[1,2-a]-quinoline-6-carbonitriles. Synlett 27:1844. https://doi.org/10.1055/s-0035-1561939

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The author would like to thank Esmat Sodagar, a postdoctoral fellow at the University of Southern California.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Abdolali Alizadeh.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 2992 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Alizadeh, A., Bagherinejad, A. Synthesis of tetracyclic pyrido-fused dibenzodiazepines via a catalyst-free cascade reaction. Mol Divers (2020). https://doi.org/10.1007/s11030-020-10114-1

Download citation

Keywords

  • Enaminone
  • Dibenzo[b,f]pyrido[1,2-d][1,4]diazepine
  • Knoevenagel condensation
  • Chemoselective
  • Three-component cascade reaction
  • Catalyst free
  • Tetracyclic ring
  • Seven-membered ring