Synthesis Of Antidiabetic Drug Omarigliptin Racemate

Nowadays,people's living standards gradually improved,while together with the improvement is the spread of various diseases.One of whom is diabetes,which has great harm to human body.With the augment in the number of diabetes prevalence,the current demand for antidiabetic drugs also increases.With the development of science and medical technology,more and more new drugs for the disease are being developed and synthesized.Wherein the dipeptidyl peptidase-4 Inhibitor(DPP-4 inhibitor),developed rapidly in recent years,is one class of new antidiabetic drugs.Omarigliptin(MK-3102)is the latest antidiabetic drugs Merck filed in 2014,belongs to DPP-4 inhibitor drugs.Compared with other similar drugs,the most significant advantage of the drug is significant growth in its half-life.In this experiment,we choose an available synthesis of Omarigliptin as a basis,aim to improve the synthetic methods.For the purpose of changing the whole route economical synthetic route,we optimize the route and improve the process parameters.In this experiment,we choose 2,5-difluorobenzaldehyde and 1-t-butoxycarbonyl-3-pyrrolidinone two substances as raw materials,respectively,according to the synthesis reaction through a series of 5-Oxo-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate and 2-(Tosyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole.Two intermediate further reacted product Omarigliptin racemate closer.In the course of the experiment,we also optimized and improved the specified synthetic route.Such as:(1)With Jones reagent to replace Dess-Martin,to save costs.(2)The use of ruthenium trichloride as a noble metal salt catalyst,instead of virulent osmium tetroxide.(3)The reaction conditions for the synthesis of compound 3-Methylene-5-nitro-6-(2,5-difluorophenyl)-3,4-dihydro-2H-pyran and compound trans-5-Methylene-3-nitro-2-(2,5-difluorophenyl)-tetrahydro-2H-pyran were optimized to increase the yield.