- Practical and economical approach to synthesize sitagliptin
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Economic syntheses of sitagliptin phosphate monohydrate, acknowledged as the first dipeptidyl peptidase 4 (DPP-4) inhibitor, have been achieved in an overall yield of 42.4% in four steps from 1-{3-(trifluoromethyl)-5,6-dihydro-[1, 2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione. The key stereoselective reduction of this process was carried out by NaBH 4/HCOOH instead of expensive and toxic catalysts or ligands. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Lin, Kuaile,Cai, Zhengyan,Zhou, Weicheng
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- Practical, asymmetric route to sitagliptin and derivatives: Development and origin of diastereoselectivity
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The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
- Gutierrez, Osvaldo,Metil, Dattatray,Dwivedi, Namrata,Gudimalla, Nagaraju,Chandrashekar,Dahanukar, Vilas H.,Bhattacharya, Apurba,Bandichhor, Rakeshwar,Kozlowski, Marisa C.
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supporting information
p. 1742 - 1745
(2015/04/14)
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- PREPARATION OF SITAGLIPTIN AND SALTS THEREOF
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Processes for preparing sitagliptin and its pharmaceutically acceptable salts, and process intermediates.
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- PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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There is provided salts and polymorphs of sitagliptin, processes for the preparation thereof, and pharmaceutical compositions comprising the same.
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Page/Page column 29
(2009/08/14)
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