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Formation of furo[3,2-c]quinolone-2-carbonitriles and 4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carboxamides from reaction of quinoline-2,4-diones with 2-[bis(methylthio)methylene]malononitrile

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Quinoline-2,4-diones reacted with 2-[bis(methylthio)methylene]malononitrile in DMF/Et3N to produce 3-(methylthio)-4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carbonitriles and 3-(methylthio)-4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carboxamides in state of 2-imino-substituted 4-(methylthio)-5,6-dihydro-2H-pyrano[3,2-c]quinolone-3-carbonitriles. The structures of all new products were proved using NMR, IR, and mass spectral data. The possible mechanism for the reaction is also discussed.

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  1. 1.

    Siddiqui N, Arshad MF, Khan SA (2009) Acta Pol Pharm 66:161

  2. 2.

    Kamiński K, Obniska J, Dybała M (2008) Eur J Med Chem 43:53

  3. 3.

    Obniska J, Kamiñski K, Tatarczyñska E (2006) Pharmcol Res 58:207

  4. 4.

    Park HB, Jo NH, Hong JH, Chei JH, Cho J-H, Yoo KH, Oh C-H (2007) Arch Pharm (Weinheim) 340:530

  5. 5.

    Fujio M, Hashimoto K, Katayama J, Numata A (2001) Preparation of spiro[azabicycloalkane-oxazolidinone] derivatives and analogs as α-7 nicotinic receptor agonists. Chem Abstr 135:318499 (WO 2001066546)

  6. 6.

    Pawar MJ, Burungal AB, Karale BK (2009) Arkivoc xiii:97

  7. 7.

    Nakao K, Ikeda K, Kurokawa T, Togashi Y, Umeuchi H, Honda T, Okano K, Mochizuki H (2008) Jpn J Psychopharmacol 28:75

  8. 8.

    Chin Y-W, Salim AA, Su B-N, Mi Q, Chai H-B, Riswan S, Kardono LBS, Ruskandi A, Farnsworth NR, Swanson SM, Kinghorn AS (2008) J Nat Prod 71:390

  9. 9.

    Schick H, Frank R, Reich M, Jostock R, Bahrenberg G, Theil F, Henkel B (2006) Preparation of 1-oxa-2,8-diazaspiro[4.5]dec-2-enes as vanilloid receptor 1 inhibitors. Chem Abstr 145:505458 (WO 2006122769)

  10. 10.

    Hu H, Guo H, Li E, Liu X, Zhou Y, Che Y (2006) J Nat Prod 69:1672

  11. 11.

    Sarma BK, Manna D, Minoura M, Mugesh G (2010) J Am Chem Soc 132:5364

  12. 12.

    Lee D, Long SA, Murray JH, Adams JL, Nuttall ME, Nadeau DP, Kikly K, Winkler JD, Sung CM, Ryan MD, Levy MA, Keller PM, DeWolf WE Jr (2001) J Med Chem 7:2015

  13. 13.

    Tan H, Wang G, Li J, Meng G, Liu Z, Dong M, Li Y, Ju D, Zhang Q (2015) Bioorg Med Chem 23:118

  14. 14.

    Lu W, Wang Y, Wang L, Zhao F, Yang S, Xi C, Yang Y, Xu L, Chi X (2018) J Mol Struct 1155:623

  15. 15.

    Aly AA, El-Sheref EM, Mourad AE, Bakheet MEM, Bräse S, Nieger M (2019) Chem Pap 73:27

  16. 16.

    Aly AA, Ramadan M, El-Reedy AAM (2019) J Heterocycl Chem 56:642

  17. 17.

    Aly AA, El-Sheref EM, Mourad AE, Brown AB, Bräse S, Bakheet MEM, Nieger M (2018) Monatsh Chem 149:635

  18. 18.

    El-Sheref EM, Aly AA, Mourad AE, Brown AB, Bräse S, Bakheet MEM (2018) Chem Pap 72:181

  19. 19.

    El-Sheref EM, Aly AA, Ameen MA, Brown AB (2019) Monatsh Chem 150:747

  20. 20.

    Aly AA, El-Sheref EM, Bakheet MEM, Mourad AE, Bräse S, Ibrahim MAA, Nieger M, Garvalov BK, Dalby KN, Kaoud TS (2019) Bioorg Chem 82:290

  21. 21.

    Aly AA, El-Sheref EM, Bakheet MEM, Mourad AE, Brown AB, Bräse B, Nieger M, Ibrahim MAA (2018) Bioorg Chem 81:700

  22. 22.

    Basco LK, Mitaku S, Skaltsounis AL, Ravelomanantsoa N, Tillequin F, Koch M, Bras JL (1994) Antimic Agents Chemother 38:1169

  23. 23.

    Cruickshank PA, Lee FT, Lupichuk A (1970) J Med Chem 13:1110

  24. 24.

    Hanawa F, Fokialakis N, Skaltsounis AL (2004) Planta Med 70:531

  25. 25.

    Marzano C, Chilin A, Baccichetti F, Bettio F, Guiotto A, Miolo G, Bordin F (2004) Eur J Med Chem 39:411

  26. 26.

    Sakharov PA, Rostovskii NV, Khlebnikov AF, Panikorovskii TL, Novikov MS (2019) Org Lett 21:3615

  27. 27.

    Calleja J, González-Pérez AB, de Lera ÁR, Álvarez R, Fañanás FJ, Rodríguez F (2014) Chem Sci 5:996

  28. 28.

    Chung P-Y, Tang JC-O, Cheng C-H, Bian Z-X, Wong W-Y, Lam K-H (2016) Springer Plus 5:271

  29. 29.

    Görlitzer K, Fabian J, Jones PG, Frohberg P, Drutkowski G (2002) Pharmazie 57:159

  30. 30.

    Buckle DR, Cantello BCC, Smith H, Spicer BA (1975) J Med Chem 18:726

  31. 31.

    El-Agrody AM, Abd-Rabboh HSM, Al-Ghamdi AM (2013) Med Chem Res 22:1339

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The authors also thank DFG Foundation for providing Prof Ashraf A. Aly, 1-month fellowship enabling him to carry out the compounds analysis in Karlsruhe Institute of Technology, Karlsruhe, Germany in July–August 2019.

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Correspondence to Ashraf A. Aly.

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Aly, A.A., Ishak, E.A., Shwaky, A.M. et al. Formation of furo[3,2-c]quinolone-2-carbonitriles and 4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carboxamides from reaction of quinoline-2,4-diones with 2-[bis(methylthio)methylene]malononitrile. Monatsh Chem 151, 223–229 (2020). https://doi.org/10.1007/s00706-019-02541-0

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  • Quinolin-2,4-diones
  • 2-[Bis(methylthio)methylene]malononitrile
  • Furo[3,2-c]quinolone-3-carbonitriles
  • Mechanism