Synthesis Process Of Dabigatran Etexilate

Dabigatran etexilate is an oral anticoagulant drug that acts as a direct thrombin inhibitor. It was developed by the pharmaceutical company Boehringer Ingelheim. Dabigatran etexilate was approved by the related administrations of Germany and the UK in April 2008 first, used to prevent the formation of blood clots in the veins who have had an operation to replace a hip or knee. This medicine has a series of virtues such as oral formulation, without special testing, potent, fewer drug interactions.The synthetic routes of dabigatran etexilate reported in the literatures were analyzed and compared, we chose 4-chloro-3-nitrobenzoic acid and 2-aminopyridine which are cheap and accessible as raw materials and synthesized dabigatran etexilate mesylate through seven chemical reactions. The following points are the main contents of the research:each reaction was optimized to improve the yield; improved the way of post treatment, simplified the operation, suitable for industrial production; the development of quality standards of intermediates and solvents and realization of control, the development of purification method of dabigatran etexilate, to ensure stable production of the API; the polymorphic forms of dabigatran etexilate mesylate was studied to ensure the crystal form of API meet the requirement of preparation.The chemical structures of all the impurities of dabigatran etexilate were identified and the synthetic routes of all impurities were designed. Synthetic impurities provided relevant information for new drug application and a reliable basis for the analysis of API.