Synthetic route and industrial preparation method of Dalilaysan

Daridorexant is a new type of dual orexin receptor antagonist ( DORA class), which is widely used to treat chronic insomnia. Its molecular design is highly selective and can regulate the balance of arousal and sleep in the central nervous system. In its industrial synthesis route, the core lies in how to construct the phenylpiperidine amide structural unit while ensuring the optical purity and activity of the final product. Generally speaking, the synthesis of dalirazolin mainly includes the following key steps: First, p-fluorophenylethylamine is used as the starting material, and through steps such as amino protection, nucleophilic substitution, condensation reaction, and cyclization, the required amide and nitrogen heterocyclic fragments are gradually introduced. The design of intermediates usually selects routes with high yield and high regioselectivity to facilitate industrial scale-up.

In industrial production, in order to meetGMP quality standards, the synthesis process of DaliRasen requires strict control of reaction conditions, such as detailed settings in catalyst selection, solvent system optimization and crystal form purification. The current mainstream process route will perform chiral separation or use a chiral catalyst in the last step to ensure isomer purity, thereby ensuring drug efficacy and safety. In addition, the use of continuous flow reaction technology has been gradually studied in the preparation of Dali Rexon, which helps to improve reaction efficiency, reduce intermediate cleaning steps, and enhance the environmental protection and economy of industrial production.

Although most of the synthesis patents for DaliRaxo are currently held by Idorsia Company, there are already many generic drug manufacturers in different countries conducting research on improving their synthesis processes in order to achieve the dual goals of efficient synthesis and cost control. As the synthesis technology matures, it is expected that the preparation method of DaliRasen will further evolve towards a green and simplified route while maintaining the active structure unchanged, providing support for subsequent industrialization and global launch.

Reference materials:https://www.quviviq.com/