Syntheses Of Organic Impurities Of Anti-peptic Ulcer Agent Of Omeprazole

Omeprazole as efficient and conventional benzimidazole ring proton pump inhibitor(PPI)that bind the H+,K+-ATP enzyme covalently can block gastric acid secretion terminal steps caused by a variety of stimuli(histamine,acetylcholine,gastrin,etc.)and produce strong inhibition of gastric acid secretion,which can be used in therapy of the gastric acid-related diseases.In recent years,the systems of new drug approval and old drug review have been gradually improved in China,which necessitates accurate and comprehensive grasping of drug-related impurities to ensure the safety and effectiveness of patients' medication.This work mainly aimed at the synthesis of three omeprazole impurities that arise from the production process,viz.Impurity ?:4-Hydroxy Omeprazole,Impurity ?:5-Desmethyl Omeprazole,and Impurity ?:N-Methyl Omeprazole.By modifying and optimizing the literature method,efficient synthetic routes towards impurities ?-? have been successfully developed.In detail,impurity ? has been achieved in two steps involving demethylation and sulfide oxidation.Impurity ? has been accessed by the use of demethylated starting reagent followed by sulfide formation and subsequent oxidation to sulfoxide.Impurity ? has been afforded through direct N-methylation of the omeprazole agent.All titled impurities have been fully characterized by 1H-NMR,ESI-MS and HPLC technique that agree well with their target structures,and can be reliably used as impurity reference for quality control of omeprazole.