Improved methodes for synthesis of midazolam drug and its analogues

In this presentation, two improved strategies for the synthesis of midazolam and analogues have been described. Midazolam has been synthesized using both strategies with isocyanide reagents in satisfactory yield. In this methodology, imidazobenzodiazepine intermediates can be easily prepared with an improved process. One-pot condensation of benzodiazepines with mono-anion of tosylmethyl isocyanide or ethyl isocyanoacetate under mild conditions led to construction of imidazobenzodiazepines structures. In the first strategy, tosylmethyl isocyanide (Tos-MIC) is used, In this methodology the number of synthetic steps has decreased to 5 steps in comparison with previous report. In the second strategy by using the ethyl isocyanoacetate which is commonly used for the synthesis of some imidazobenzodiazepines, this drug synthesized. The next, is a relatively different method for the synthesis of midazolam analogues has been reported.

Keywords:

midazolam , tosylmethyl isocyanide , ethyl iso cyanoacetate , annulation , imidazo[1 , 5-a][1 , 4]benzodiazepines