Abstract
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 NaBH4/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.]
GRAPHICAL ABSTRACT
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ACKNOWLEDGMENT
This work was supported by the 973 Program of the Ministry of Science and Technology of China (2010CB735601 and 2012CB724501).
Notes
a Reducing agent was prepared in THF.
b The ratios were determined by HPLC analysis.
c At the end of reaction, the enaminoamide 4a was detected as the biggest spot by TLC.
a Reducing agent was prepared in THF.
b The ratios were determined by HPLC analysis.