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.
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