Optimization Of The Synthesis Of Dabigatran Etexilate As A New Novel Oral Anticoagulants

Thromboembolic disorders are the major of threat to modern humans’health, which have the characteristic of hereditary, recurrent and increasingly younger. The pathogenesis of thrombus is very complex, which hasn’t been absolutely elucidated; but it has been found that related to several factors, such as vascular endothelial injury, increased blood coagulation.The antithrombotic drugs are increasingly becoming the first choice for treatment of Thromboembolic disorders, which for the advantage of specificity, be oral (except heparin), the predictable Anticoagulation effect and so on. However, the most anticoagulants drugs have the drawback of inconvenient, application population stenosis and drugs interactions. Dabigatran etexilate as an novel non-peptide inhibitors of anticoagulant, has the advantage of safe and effective, application population widely, could be administered orally, don’t need rigorous clinical observation. The market respone is good since on its sale and it will be has a broad market prospects.Dabigatran etexilate has been sold in Europe, America, Japan and many countries and regions at present, which was sold in China since 2013. In recent years, the synthesis route of dabigatran etexilate has becom anticoagulants field hotspots. Given the drawbacks of sources of raw materials difficulties, higher costs and lower yields to synthesis dabigatran etexilate, we design a route to synthesis of dabigatran, which use using 2-aminopyridine as raw material via Michael addition, chloride, amidation, catalytic hydrogenation, condensation off the ring, cyano aminolysis and esterification to afford the target compounds. The yield increased by 12.5% to 39%. This route has the advantage of mild reaction conditions, simple operation, high yield and more suitable for industrial production.The IR,1HNMR,13CNMR, MS is used to determine the structure of the product.