Abstract
A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application.
The highly telescoped process involves only three intermediate isolations over a 12-step sequence.
The dioxa-bicyclo[3.2.1]octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-d-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step.
The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide.
High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with l-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.
Citing Articles
View all 1 citing articlesCitation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 1 ACS Journal articles (1 most recent appear below).
Development and Scale-Up of Cocrystals Using Resonant Acoustic Mixing
David J. am Ende, Stephen R. Anderson, and Jerry S. SalanOrganic Process Research & Development2014 18 (2), 331-341
0 件のコメント:
コメントを投稿