The Synthesis And Qualitive Research Of Moguisteine

Moguisteine [(+/-)-2-(2-Methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl-1,3-thiazolidine], a new oral nonnarcotic peripherally antitussive agent which belong to acetylcholine receptor antagonists,has been developed by dompe company and introduced to intaly market in 2004.This study included of the synthetic work,structure confirmation and qualytitive analysis of moguisteine.The synthetic process use guaiacol and Bromoacetaldehyde dimethyl acetal as raw material,was synthesized by sustitution,cyclization,N-acylation according to reference. In the process of substitution,orthogonal test was used for ensuring the opitimal conditions for the reaction:reaction time is 4h,reaction temperature is 150℃, the mol ration of guaiacol and Bromoacetaldehyde dimethyl acetal is 1:1.15. In the process of cyclization,we optimized the ration of 1-(2,2-d imethoxyethoxy) 2-methyl phenyl ether and cysteamine hydrochloride,at last, the ration determined is 1:10. In the process of N-acylation,we optimized the acid-accepter and the roation of 2-[(2-methoxyphenoxy)-methyl-1,3 thiazolidine and eomalonyldichloride is 1: 1.12.These improvements increased overall yield to 65.9%. the synthetic route have pratical advantages,such as brief reaction steps, convenient manipulation and low cost.The structure of moguisteine was performed by elemental analyzed, IR,UV, magnetic resonance, mass spectrometry.According to the requirement of China Pharmacopeia, the qualitative research of mguisteine has been done. The melting point, solubility and other physical and chemical constans were determined. The possible impurities and assaying were checked by HPLC, and a comprehensive qualitive study were carried out, estblishing a standard on the entire inspection and limited quatity.