The Study On The New Synthesis Method Of Irbesartan And Process Optimization

In the 2020s,in the era of 5G network,information is updated with each passing day,which will bring more and more pressure to the life and work of the working class.Cardio-cerebrovascular diseases,especially(essential)hypertension,as the highest mortality rate in the world,have become one of the diseases that cannot be underestimated.At present,drug treatment is still the preferred method of the clinical treatment of hypertension,and Sartan drugs are one of the classic antihypertensive drugs.As an angiotensin II receptor antagonist drug mainly used for the treatment of essential hypertension in adults,Irbesartan has been unanimously recognized by patients and doctors due to its obvious efficacy and few adverse reactions.We have designed a new synthesis route of Irbesartan.One of the important design ideas is based on the high activity of the ?-methylene group on the amide fragment,allowing it to react with 1,4-dibromobutane in an alkaline environment to build an N-helix ring system.The route selects cheap and easily available glycine methyl ester hydrochloride as the starting material,and the final target compound Irbesartan is obtained through five steps of acylation,transesterification,nucleophilic addition-elimination,alkylation,and azide.After the successful of the test in the laboratory,a series of process optimizations were performed on the synthesis and post-treatment of some key intermediates in the route to improve the yield,and the final total yield of Irbesartan can reach 36%.After that,a pilot scale-up experiment was conducted.At the same time,a new construction method of imidazole ring system different from the above route was proposed in the exploration.The route proposed in this paper not only reduces cost control,but also avoids the use of highly toxic cyanide,and is environmentally friendly,with lower energy consumption and higher yield.The pilot scale-up experiment has a great reference for future industrial production.It is believed that Irbesartan will have a greater application in the treatment of essential hypertension in the future.