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

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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.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Imam Hossein, Tehran, Islamic Republic of Iran

    Mohammad Javad Taghizadeh, Gholam reza malakpouri & Abdollah Javidan

  2. Eyvanekey University, Eyvanekey, Islamic Republic of Iran

    Abdollah Javidan

Authors
  1. Mohammad Javad Taghizadeh
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  2. Gholam reza malakpouri
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  3. Abdollah Javidan
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Correspondence to Mohammad Javad Taghizadeh.

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Taghizadeh, M.J., malakpouri, G.r. & Javidan, A. Improved and scalable methods for the synthesis of midazolam drug and its analogues using isocyanide reagents. J IRAN CHEM SOC 16, 785–794 (2019). https://doi.org/10.1007/s13738-018-1555-0

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