Study On Synthesis And Quality Standards Of Linagliptin

Diabetes mellitus is one of the major global diseases,and the number of patients is increased year by year.Traditional hypoglycemic drugs can no longer meet the increasing demand of hypoglycemic drugs market.With the deepening of studies on hypoglycemic drugs,a series of new hypoglycemic drugs have been developed successfully,dipeptide base peptidase 4(DPP-4)as T2 DM treatment of new drugs,with its good safety and tolerability advantages,has gradually become one of the main hypoglycemic drugs.At present,among the DPP-4 inhibitors listed in China,Linagliptin has been ranked the fourth in the oral hypoglycemic drug market in China,although it was late to be marketed.This topic in 8-bromine-7-(2-butyl alkynyl)-3,7-dihydro-h-3-methyl-1)-2,6-2 ketone as the starting material,after substitution reaction,take off the protective reaction and recrystallization is lige column crystal A,statins to various intermediates1H-NMR analysis,the obtained lige column crystal statins A for 1H-NMR,13C-NMR,MS,X-ray,DSC analysis,the whole experiment route total yield reached 64.3%.This study focused on the study on the removal of rigoletin N-Boc,and obtained two innovative methods: silica gel-toluene catalytic deprotection,acetyl chloride and ethanol reaction to obtain HCl deprotection,which has higher yield,easier experimental treatment and is more suitable for large-scale production.In this paper,according to the registration standard of imported drugs of rigoliptin and the synthetic route of this paper,the possible impurities detected in Linagliptin were determined,and the impurities 16,17,31,32 and 33 were synthesized by directional synthesis,and each impurity was analyzed by 1H-NMR.The appearance,solubility and specific rotation of ligustine were investigated simultaneously.It uses HPLC method to carry out relevant substances and content determination on Linagliptin.that system's adaptability,linearity,stability,repeatability and precision were observe in the other methods.the results were good,and the quality control for Linagliptin was found,and the purity of the decometincrystal A was higher than 99.5%,and the Linagliptin contained no S-configuration compound.Generally speaking,this topic is the synthetic route has the synthetic cycle short,simple test operation,the advantages of high yield,low cost,low pollution,is a very suitable for large-scale production of industrial route.