Study Of The Synthesis Of Losartan Potassium

Losartan Potassium, as a biphenyltetrazole angiotensin II receptor antagonist, was developed by Merck Co. and ratified by FDA for antihypertensive, with the characterstics of long-lasting, good tolerance and high receptor-selectivity.The project aims to study synthesis of Losartan Potassium. Valeronitrile and 2-cyano-4'-methylbiphenyl as the starting materials, Losartan Potassium was synthesized successfully via a eight-step route with overall yields 31.59%. Its structure was identified by the data of IR and1H-NMR.1-methoxy-1-imine pentane (2) was synthesized with methanol and valeronitrile as raw materials, and catalyzed by sodium methoxide, after substitution with glycine to give (Pentanimidoylamino) acetic acid (3).without the requirement of an isolation or purification. this route was suitable for large-scale preparation for its mild reaction conditions, and without hydrogen chloride gas.2-n-butyl-4-chloro-1-[2'-(cyanobiphenyl-4-yl)methyl]-5-(hydroxymethyl)-imidazole (7) was prepared by"one pot"method via three steps including bromination reaction, N-alkylation and reduction. The procedure was simple and the production cost was lowed.The target product Losartan Potassium (1) was synthesized by the combination of intermediates(7) via steps including [3+2] cyclization reaction and neutralization reaction. This new method was improved and that can be operated easily,reaction condation moderate,higher yield(31.48%) and more suitable for industrial production. This method has not been reported by far.