Synthetic method of 5-(4'-methyl-[1,1'-biphenyl]-2-yl)-1hydro-tetrazole

Abstract

The invention discloses a synthesis method of 5-(4'-methyl-[1,1'-biphenyl]-2-yl)-1-hydro-tetrazole, which comprises the following steps: by using 2-carboxy-4'-methyl biphenyl as the raw material, reacting with excessive thionyl chloride under reflux conditions, depressurizing to remove excess thionyl chloride, and carrying out acylation reaction on benzsulfamide to obtain a product III; reacting the product III with phosphorous pentachloride by using carbon tetrachloride as a solvent to obtain an imino acyl chloride derivative IV; carrying out substitution reaction on the imino acyl chloride derivative IV and hydrazine hydrate to obtain a product V; and finally, carrying out cyclization on the product V and sodium nitrate under acidic conditions, and carrying out benzenesulfonyl removal reaction to obtain the 5-(4'-methyl-[1,1'-biphenyl]-2-yl)-1-hydro-tetrazole. The method has the advantages of mild reaction conditions, high safety and high efficiency.

Description

technical field [0001] The invention relates to a synthesis method of 5-(4'-methyl-[1,1'-biphenyl]-2-yl)-1 hydrogen-tetrazole. Background technique [0002] Among the drugs for the treatment of hypertension, sartan drugs have the characteristics of significant antihypertensive effect, small side effects, good persistence and high safety. Since losartan was launched in Sweden in 1994, sartan, irbesartan, Candesartan and other sartan drugs have been launched one after another, and these drugs quickly occupied the antihypertensive drug market due to their remarkable therapeutic effect. 5-(4'-Methyl-[1,1'-biphenyl]-2-yl)-1 hydrogen-tetrazole is a key intermediate in the synthesis of sartan drugs, and the improvement of its synthesis process has a great impact on the whole sartan class Drug development is of great significance. [0003] The following two methods are generally adopted at home and abroad at present: one is to take nitrile as raw material and sodium azide as raw m...

AI Technical Summary

Problems solved by technology

[0003] The following two methods are generally adopted at home and abroad at present: one is to take nitrile as raw material and sodium azide as raw material, prepare in organic solvent with amine or amine salt catalyst, sodium azide in the method is easy to explode, and Its contact with acid will produce extremely toxic azido acid; another way is to use tin azide intermediate to react with nitrile, the method yield is relatively high, but tin azide is a highly toxic reagent, and tin is a heavy metal substance , tends to remain in the final product

It can be seen that these methods are extremely inconvenient for raw material transportation and storage, and there are also potential safety hazards in drug production.

Images