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Improved and scalable methods for the synthesis of midazolam drug and its analogues using isocyanide reagents

  • Mohammad Javad TaghizadehEmail author
  • Gholam reza malakpouri
  • Abdollah Javidan
Original Paper
  • 15 Downloads

Abstract

In this research, two improved and scalable methods for the synthesis of midazolam and its analogues have been described. Midazolam has been synthesized using isocyanide reagents in satisfactory yield. In this methodology, imidazobenzodiazepine intermediates can be easily prepared via an improved process. One-pot condensation of benzodiazepines with mono-anion of tosylmethyl isocyanide or ethyl isocyanoacetate under mild condition led to formation of imidazobenzodiazepine. In the first method, tosylmethyl isocyanide (Tos-MIC) is used and the number of synthetic steps are decreased in comparison to previous report. In the second method, ethyl isocyanoacetate which is commonly used for the synthesis of some imidazobenzodiazepines, is consumed to generate midazolam. The latter, a relatively different method for the synthesis of midazolam analogues has been reported.

Graphical abstract

Keywords

Midazolam Tosylmethyl isocyanide Ethyl isocyanoacetate Annulation Imidazo[1,5-a][1,4]benzodiazepines 

Supplementary material

13738_2018_1555_MOESM1_ESM.docx (19.6 mb)
Supplementary material 1 (DOCX 20113 KB)

References

  1. 1.
    J.R. De Baun, F.M. Pallos, D.R. Baker, US Patent 3978227 (1976)Google Scholar
  2. 2.
    H. Schultz, Benzodiazepines (Springer, Heidelberg, 1982)CrossRefGoogle Scholar
  3. 3.
    R.K. Smiley, Comprehensive Organic Chemistry (Pergamon, Oxford, 1979)Google Scholar
  4. 4.
    J.K. Landquist, Comprehensive Heterocyclic Chemistry, vol. 1 (Pergamon, Oxford, 1984), pp. 166–170Google Scholar
  5. 5.
    L.O. Randall, B. Kappel, Benzodiazepines (Raven Press, New York, 1973)Google Scholar
  6. 6.
    D.A. Horton, G.T. Bourne, M.L. Smythe, Chem. Rev. 103, 893 (2003)CrossRefGoogle Scholar
  7. 7.
    M. Anzini, C. Braile, S. Valenti, A. Cappelli, S. Vomero, L. Marinelli, V. Limongelli, E. Novellino, L. Betti, G. Giannaccini, A. Lucacchini, C. Ghelardini, M. Norcini, F. Makovec, G. Giorgi, R. Ian, Fryer, J. Med. Chem. 51, 4730 (2008)CrossRefGoogle Scholar
  8. 8.
    E. Sigel, Curr. Top. Med. Chem. 2, 833 (2002)CrossRefGoogle Scholar
  9. 9.
    J. Dourlat, W.-Q. Liu, N. Gresh, C. Garbay, Bioorg. Med. Chem. Lett. 17, 2527 (2007)CrossRefGoogle Scholar
  10. 10.
    L.O. Randall, Psychopharmacological Agents, vol. 3 (Academic Press, New York, 1974), pp. 175–281CrossRefGoogle Scholar
  11. 11.
    D.J. Greenblatt, R.I. Shader, Benzodiazepines in Clinical Practice (Raven Press, New York, 1974), pp. 183–196Google Scholar
  12. 12.
    L.O. Randall, B. Kappell, The Benzodiazepines (Raven Press, New York, 1973), pp. 27–51Google Scholar
  13. 13.
    M.G. Block, R.M. DiPardo, B.E. Evans, K.E. Rittle, W.L. Witter, D.F. Veber, P.S. Anderson, R.M. Freidinger, J. Med. Chem. 32, 13 (1989)CrossRefGoogle Scholar
  14. 14.
    L.H. Sternbatch, Drugs Affecting the Central Nervous System, vol. 2 (Marcel Dekker, New York, 1968), pp. 237–264Google Scholar
  15. 15.
    W. Sneader, Comprehensive Medicinal Chemistry, vol. 1 (Pergamon, London, 1990), p. 65Google Scholar
  16. 16.
    G. Moroz, J. Clin. Psychiatry 65, 13 (2004)PubMedGoogle Scholar
  17. 17.
    J.A. Vida, Principles of Medicinal Chemistry (Wiley, New York, 1981), pp. 144–170Google Scholar
  18. 18.
    R.I. Frier, in In Comprehensive Heterocyclic Chemistry, vol. 3, ed. by B.C. Hansch (Pergamon Press, New York, 1990), p. 539Google Scholar
  19. 19.
    J.K. Landquist, In Comprehensive Heterocyclic Chemistry (Pergamon Press, Oxford, 1984)Google Scholar
  20. 20.
    J.B.Jr. Hester, In Antianxiety Agents, ed. by Berger B.J.G. (Wiley, New York, 1986), p. 51Google Scholar
  21. 21.
    J.B. Hester, A.B. Rudzik, B.V. Kamdar, J. Med. Chem. 14, 1078 (1971)CrossRefGoogle Scholar
  22. 22.
    A.M. El-Sayed, H. Abdel-Ghany, A.M.M. El-Saghier, Synth. Commun. 29, 3561 (1999)CrossRefGoogle Scholar
  23. 23.
    J.X. Xu, H.T. Wu, S. Jin, Chin. J. Chem. 17, 84 (1999)CrossRefGoogle Scholar
  24. 24.
    X.Y. Zhang, J.X. Xu, S. Jin, Chin. J. Chem. 17, 404 (1999)CrossRefGoogle Scholar
  25. 25.
    K. Kim, S.K. Volkman, J.A. Ellman, J. Braz. Chem. Soc. 9, 375 (1998)Google Scholar
  26. 26.
    S. Fustero, J. González, C. Del Pozo, Molecules 11(8), 583 (2006)CrossRefGoogle Scholar
  27. 27.
    R.Y. Ning, R.I. Fryer, P.B. Madan, B.C. Sluboski, J. Org. Chem. 41(16), 2724 (1976)CrossRefGoogle Scholar
  28. 28.
    A. Walser, L.E. Benjamin, T. Flynn, C. Mason, R. Schwarts, R.I. Fryer, J. Org. Chem. 43, 936 (1978)CrossRefGoogle Scholar
  29. 29.
    Walser et al., J. Org. Chem. 43(5), 936 (1978)CrossRefGoogle Scholar
  30. 30.
    G.F. Field, US Patent 4194049 (1980)Google Scholar
  31. 31.
    J.M. Khann, EP Patent 0835874 (1998)Google Scholar
  32. 32.
    J.E. Huber, US Patent 5831089 (1998)Google Scholar
  33. 33.
    K. Bender, EP Patent 768310 (1997)Google Scholar
  34. 34.
    S. Krivonos, Y. Sery, US Patent 7776852 (2010)Google Scholar
  35. 35.
    A. Walser, US Patent 4226771 (1980)Google Scholar
  36. 36.
    Y. Zhang, P.W.K. Woo, J. Hartman, N. Colbry, Y. Huang, C.C. Huang, Tetrahedron Lett. 46, 2087 (2005)CrossRefGoogle Scholar
  37. 37.
    J.M. Cook, Q. Huang, X. He, X. Li, J. Yu, D. Han, S. Lelas, J.F. McElroy, US Patent 7119196 (2006)Google Scholar
  38. 38.
    X. He, X. Li, J. Yu, D. Han, J. Cook, Q. Huang, US Patent 11/767515 (2007)Google Scholar
  39. 39.
    G. Broggini, M. Orlandi, A. Turconi, C. Zoni, Org. Prep. Proc. Int. 35(6), 609 (2003)CrossRefGoogle Scholar
  40. 40.
    S.R. Donohue, R.F. Dannals, Tetrahedron Lett. 50(52), 7271 (2009)CrossRefGoogle Scholar
  41. 41.
    A. Walser, US Patent 4118386 (1978)Google Scholar
  42. 42.
    B.C. Lee, B.S. Moon, J.S. Kim, US Patent 8895727 (2014)Google Scholar
  43. 43.
    F. Watjen, R. Baker, M. Engelstoff, R. Herbert, A. MacLeod, A. Knight, K. Merchant, J. Moseley, J. Saunders, J. Med. Chem. 32(10), 2282 (1989)CrossRefGoogle Scholar
  44. 44.
    J.M. Cook, D. Han, T. Clayton, US Patent 7595395 (2009)Google Scholar
  45. 45.
    A. del Pozo, E. Macias, J. Alonso, Gonzalez, Synthesis. 16, 2697 (2004)CrossRefGoogle Scholar
  46. 46.
    J. Yang, Y. Teng, S. Ara, S. Rallapalli, J.M. Cook, Synthesis. 40(32), 1036 (2009)Google Scholar
  47. 47.
    Z.Q. Gu, G. Wong, C. Dominguez, B.R. de Costa, K.C. Rice, P. Skolnick, J. Med. Chem. 36(8), 1001 (1993)CrossRefGoogle Scholar
  48. 48.
    P. Zhang, W. Zhang, R. Liu, B. Harris, P. Skolnick, J.M. Cook, J. Med. Chem. 38(10), 1679 (1995)CrossRefGoogle Scholar
  49. 49.
    K. Kyungjin, S.K. Volkman, J.A. Ellman, J. Braz. Chem. Soc. 9(4), 375 (1998)CrossRefGoogle Scholar
  50. 50.
    M. Cepanec, I. Litvić, Pogorelić, Org. Process Res. Dev. 10(6), 1192 (2006)CrossRefGoogle Scholar
  51. 51.
    P. Cheng, Q. Zhang, Y.B. Ma, Z.Y. Jiang, X.M. Zhang, F.X. Zhang, J.J. Chen, Bioorg. Med. Chem. Lett. 18(13), 3787 (2008)CrossRefGoogle Scholar
  52. 52.
    M. Hannoun, M. Žinić, D. Kolbah, F. Kajfež, N. BlaŽević, J. Heterocycl. Chem. 18(5), 963 (1981)CrossRefGoogle Scholar
  53. 53.
    H. Sati, S. Sati, P.C. Saklani, R. Bhatt, Mishra, Acta. Pharm. 63(3), 385 (2013)CrossRefGoogle Scholar
  54. 54.
    N. Blažević, F. Kajfež, J. Heterocycl. Chem. 8(5), 845 (1971)CrossRefGoogle Scholar
  55. 55.
    B. Narayana, K.V. Raj, B.V. Ashalatha, N.S. Kumari, Eur. J. Med. Chem. 41(3), 417 (2006)CrossRefGoogle Scholar
  56. 56.
    L.H. Sternbach, Angew. Chem. Int. Ed. Engl. 10(1), 34 (1971)CrossRefGoogle Scholar
  57. 57.
    Y. Zhang, P.W. Woo, J. Hartman, N. Colbry, Y. Huang, C.C. Huang, Tetrahedron Lett. 46(12), 2087 (2005)CrossRefGoogle Scholar
  58. 58.
    M. Rogers-Evans, P. Spurr, M. Hennig, Tetrahedron Lett. 44(11), 2425 (2003)CrossRefGoogle Scholar
  59. 59.
    M. Rogers-Evans, P. Spurr, US Patent 5670640 (1997)Google Scholar
  60. 60.
    R.I. Fryer, Z.Q. Gu, C.G. Wang, J. Heterocycl. Chem. 28(7), 1661 (1991)CrossRefGoogle Scholar
  61. 61.
    A. Walser, A. Guidotti, E. Costa, US Patent 5317018 (1994)Google Scholar
  62. 62.
    A. Walser, US Patent. No. 4118386 (1978)Google Scholar
  63. 63.
    M.K. Dhaon, G.L. Esser, D.A. Davis, A.V. Bhatia, US Patent 6512114 (2003)Google Scholar
  64. 64.
    K.H. Bender, M. Breuninger, M. Froom, S. Schmitt, K. Steiner, US Patent 5693795 (1997)Google Scholar
  65. 65.
    M.K. Dhaon, US Patent 6262260 (2001)Google Scholar
  66. 66.
    A. Castellin, M. Maggini, P. Donnola, US Patent 8557981 (2013)Google Scholar

Copyright information

© Iranian Chemical Society 2018

Authors and Affiliations

  • Mohammad Javad Taghizadeh
    • 1
    Email author
  • Gholam reza malakpouri
    • 1
  • Abdollah Javidan
    • 1
    • 2
  1. 1.Department of Chemistry, Faculty of ScienceUniversity of Imam HosseinTehranIslamic Republic of Iran
  2. 2.Eyvanekey UniversityEyvanekeyIslamic Republic of Iran

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