The Research On The Synthesis And Quality Of Olmesartan Medoxomil

Olmesartan medoxomil,whose chemical name is 4-(1-hydroxy-l-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]m ethyl]-1H-imidazole-5-carboxylic acid(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester,is a drug developed by SankyoPharma in Japan used for the treatment of hypertension,and it was first marketed in the United States in 2002.Ethyl-4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate and 5-(4'-bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1 H-tetrazole are used as starting materials,through the reaction of condensation and hydrolysis to obtain the intermediate.Then the intermediate via the esteritication with 4-cloromethyl-5-methyl-1,3-dioxol-2-one to get trityl olmesartan medoxomil,which followed with the reaction of deprotection to get the crude product.Finally,olmesartan medoxomil is obtained through recrystallization with total yield of 65%,purity of 99.8%,and the largest single impurity is less than 0.1%.The research work mainly includes two parts.The first part is the optimization of the synthesis processes,which involves the optimization of the parameters in each step.The second part is the relevant quality research work for the registration approval,involving the characterization of olmesartan medoxomil,synthesis of impurities,traceability of impurities and validation of analytical methods.