767340-03-4Relevant articles and documents
Two methods for the preparation of sitagliptin phosphate: Via chemical resolution and asymmetric hydrogenation
Ye, Fei,Zhang, Zhifeng,Zhao, Wenxia,Ding, Jianhai,Wang, Yali,Dang, Xueyan
, p. 4805 - 4809 (2021/02/03)
Two effective processes have been developed for the preparation of sitagliptin phosphate. The approach of chemical resolution obtained R-sitagliptin in five steps from commercially available starting materials using the inexpensive NaBH4 to reduce the enamine and then using (-)-di-p-toluoyl-l-tartaric acid to resolve racemates in 11% yield overall. The route successfully avoids the use of expensive noble metal as catalysts compared with traditional synthesis methods, resulting in greatly reduced costs and simplified synthetic routes. Other alternative asymmetric hydrogenation of β-ketomide routes for the synthesis of sitagliptin were found, two of the intermediates were synthesized for the first time. This journal is
NOVEL PROCESS FOR THE PREPARATION OF DIPEPTIDYL PEPTIDASE-4 (DPP-4) ENZYME INHIBITOR
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Page/Page column 15; 16, (2016/08/10)
The present invention relates to a novel and improved process for the preparation of Sitagliptin of Formula (I) and its pharmaceutically acceptable salts. The present invention also relates to novel intermediates and process for the preparation of intermediates used in the preparation of Sitagliptin.
Highly efficient asymmetric synthesis of sitagliptin
Hansen, Karl B.,Hsiao, Yi,Xu, Feng,Rivera, Nelo,Clausen, Andrew,Kubryk, Michele,Krska, Shane,Rosner, Thorsten,Simmons, Bryon,Balsells, Jaume,Ikemoto, Nori,Sun, Yongkui,Spindler, Felix,Malan, Christophe,Grabowski, Edward J. J.,Armstrong III, Joseph D.
experimental part, p. 8798 - 8804 (2009/12/04)
A highly efficient synthesis of sitagliptin, a potent and selective DPP-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM), has been developed. The key dehydrositagliptin intermediate 9 is prepared in three steps in one pot and directly isolated in 82% yield and >99.6 wt % purity. Highly enantioselective hydrogenation of dehydrositagliptin 9, with as low as 0.15 mol % of Rh(I)/tBu JOSIPHOS, affords sitagliptin, which is finally isolated as its phosphate salt with nearly perfect optical and chemical purity. This environmentally friendly, 'green' synthesis significantly reduces the total waste generated per kilogram of sitagliptin produced in comparison with the first-generation route and completely eliminates aqueous waste streams. The efficiency of this cost-effective process, which has been implemented on manufacturing scale, results in up to 65% overall isolated yield.