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

Abstract

The reported methods for the synthesis of midazolam include a number of disadvantages, such as high production cost and low yields. The purpose of this investigation was to develop a more economical and technically more feasible route to synthesis of midazolam. In this research, two easy and scalable synthetic methods for the production of midazolam drug 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 synthesized. These imidazo-type structures can be derivatives by the alkylation of the imidazole ring with tert-butyl magnesium chloride at 0 °C in excellent yield, which have not been described for these intermediates in the literatures.