Study On The Synthesis Of Saxagliptin And Olmesartan Medoxomil's Related Substances

Diabetes is one of the global chronic metabolic diseases,the number of patients was significantly increased in recent years and the total number of people with diabetes worldwide is expected to reach 438 million in 2030.There were 5.1 million people died of diabetes and the health spending was more than 500 billion dollars in 2013.Saxagliptin is a new kind of dipeptidyl peptidase IV inhibitor of new target for drug development in recent years.Numerous clinical trials indicate it has good hypoglycemic effect,easy administration,few adverse reaction,and the incidence of hypoglycemia was similar to placebo,exhibiting broad market prospects as one kind of oral antidiabetic drugs.The synthetic route of Saxagliptin was determined by consulting related literatures.Saxagliptin was synthesized from N-Boc-L-cis-4,5-methanoprolineamide via deprotection to get it's methylsulfonic acid salt,which was condensation with?S?-N-Boc-3-hydroxyadamantylglycine to yield tert-butyl??S?-2-??1S,3S,5S?-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl?-1-??1R,3R,5R,7S?-3-hydroxyadamantan-1-yl?-2-oxoethyl?carbamate.Treatment of it with trifluoroacetic anhydride,followed by Boc-deprotection and worked up to afforded the Saxagliptin.Each step of the process parameters were optimized and investigated reaction temperature,time,crystallization solvents on the reaction.The improved process has the advantages of simple operation,convenient workup,and the total yield of 39.9%.The target compound and intermediates were confirmed by the technology of Infrared spectroscopy?IR?,Nuclear magnetic resonance spectroscopy(¹H NMR and¹³C NMR)and Mass spectra.In order to meet the raw material medicine and preparation quality control requirements,synthetic study were conducted on the related substances of Olmesartan medoxmoil.Their substances were confirmed by ¹H NMR and¹³C NMR.