efficient and scalable methods for synthesis of midazolam drug with an annulation process

The reported methods for the synthesis of midazolam include a number of disadvantages, such as high production costs and low yields. the purpose of this investigation was to develop a more economical and technically feasible route to the synthesis of midazolam. in this research, two easy and scalable synthetic methods for the production of midazolam drugs are presented. one-pot condensation of imidoyl chloride or 1,4-benzodiazepinic n-nitrosoamidines with carbanion of two isocyanide reagents is described and two important and key tricyclic ring intermediates are synthesized. these imidazole-type structures can be derivatives by the alkylation of the imidazole ring with tert-butyl magnesium chloride at 0 °c in excellent yield, which has not been described for these intermediates in the literature.