Study On New Synthesis Process Of Irbesartan

With the improvement of people’s living standards and changes in diet,hypertension has become the most common cardiovascular disease,the number of diseases showed a rising trend year by year,The age of illness is also decreasing year by year,affect the quality of work and life,if not controlled will cause harm to the body and serious complications.At present,the treatment of hypertension is mainly controlled by drugs.Antihypertensive drugs can be divided into six categories according to the different mechanism of action.Irbesartan is a kind of angiotensin II receptor antagonist.Irbesartan was developed by Sanofi,The earliest in 1997 in Europe and the United States sales。Irbesartan be used for the treatment of essential hypertension,As a component of antihypertensive drug be used for the the treatment of hypertension and type 2 diabetic nephropathy.At present,the sartan drugs,irbesartan sales ranked second,has a vast market space.In order to reduce costs,reduce waste generation,to study the Irbesartan new synthesis process,has great economic benefits and environmental benefits.In past studies,synthesis of the mainstream,with cyclopentanone as starting material,cyclopentanone reacted with sodium cyanide,obtained 1-amino ring valeronitrile oxalate,further obtained 2-butyl-1,3-diazaspiro[4,4]non-1-en-4-one,and reacted with 2-Cyano-4’-Bromomethylbiphenyl,reacted with sodium azide,obtaned Irbesartan.The method uses cyanide,It is a highly toxic substance,has a greater harm to the environment and workers.The goal of this study is to design a new synthetic method to avoid the use of highly toxic cyanide.The first method,glycine as the starting material,2-butyl-3-(4’-Bromobenzyl)-1,3-diazaspiro[4,4]non-l-en-4-one was obtaned by esterification,amidation,dehydration condensation and cyclizetion,and coupled with 2-[N-(triphenylmethyl)-tetrazole]phenylboric acid by SUZUKI reaction,take off the protective group,get irbesartan.However,in the process of synthesis,dehydration condensation reaction is failed.The second method,4-bromobenzylamine as the starting material,reacted with.ethyl formate,reacted with phosphorus oxychloride,obtained 4-brominebenzyl-isocyanide.Then,cyclopentanone,ammonia and pentanoic acid reacted with 4-bromine benzyl-isocyanide by Ugi reaction,obtained 2-butyl-3-(4’-Bromobenzyl)-1,3-diazaspiro[4,4]non-1-en-4-one,and coupled with 2-[N-(triphenylmethyl)-tetrazole]phenylboric acid by SUZUKI reaction,take off the protective group,get irbesartan.It is an innovative new route.