Synthesis Study Of Anti-platelet Aggregation Drugs Prasugrel

With the increasing work pressure and accelerated pace of modern life,the long time of dietary problems and no reasonable arrangments exercise at the same time,Cardiovascular Diseases has become a multiple disease,seriouly harm to people?s physical and mental health and reducing the quality of people?s life.Prasugrel is a kind of Thiophene pyridine drugs,also the analogues of Clopidogrel,which chemical name is 5-(alpha cyclopropyl carbonyl-2-phenyl)-2-acetoxyl group-4,5,6,7-tetrahydrothiophene(3,2-c)pyridine,is developed by Japan's three companies and Eli Lilly and Company,Used in the treatment of percutaneous coronary treatment(PCI)and acute coronary syndrome(ACS)in patients with artery atheromatous thrombosis,has been approved by the FDA,and was approved in the European Union on February 23,2009.The drug has quick effect,strong function,high curative effect,blood drug concentration stable,persistent,individual difference is small,the less cardiovascular adverse events characteristics.Prasugrel?s launch gives patients with cardiovascula disease a large of Gospel.The thesis mainly focuses on the process study of prasugrel.The realated references show that the preparation of prasugrel mainly includes the synthesis of two intermediates,namely 2-oxygen generation-2,4,5,6,7,7a-six hydrogen pyridine and [3,2-c] thiophen hydrochloride.At the same time,most of the references use some expensive raw materials?strict operation condition and longer reaction route to prepare the final product prasugrel,but it?s not suitable for industrial production.So,a new,simple,total synthetic route which has lower cost and less operation steps was got on the basis of the route which has been reported.Fiuorobenzyi bromide were used as starting materials to generate 4 via Grignard reaction and bromination reaction,then condensation with 4,5,6,7-tetrahydrothiophene [3,2-c] pyridine hydrochloride,which the intermediate via oxidizing reaction and acetylation reaction get the final production prasugrel.Reaction conditions of each step were optimized to get the optimal reaction conditions.The process had the cheap raw materials,mild condition,simple operation to make it more suitable for the industrial scale production.The total yield of the route reach to 23.4%.The chemical structure of prasugrel and its intermediates were confirmed by ~1H-NMR and MS.