Development of a Kilogram-Scale Asymmetric Synthesis of a Potent DP Receptor Antagonist

An efficient asymmetric synthesis of a unique sulfenylated prostaglandin DP receptor antagonist candidate is described. The synthesis is characterized by a novel intramolecular Friedel−Crafts cyclization of an imino-pyrrole to prepare the azaindole core. Other key steps include a highly selective Ho...

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Bibliographic Details
Published in:Organic process research & development 2010-07, Vol.14 (4), p.787-798
Main Authors: Tudge, Matthew, Savarin, Cecile G, DiFelice, Katherine, Maligres, Peter, Humphrey, Guy, Reamer, Bob, Tellers, David M, Hughes, Dave
Format: Article
Language:English
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Summary:An efficient asymmetric synthesis of a unique sulfenylated prostaglandin DP receptor antagonist candidate is described. The synthesis is characterized by a novel intramolecular Friedel−Crafts cyclization of an imino-pyrrole to prepare the azaindole core. Other key steps include a highly selective Horner−Wadsworth−Emmons olefination of a tricyclic ketone intermediate and subsequent catalytic asymmetric hydrogenation of a trisubstituted α,β-unsaturated ester to install the chirogenic center. Finally, a new indole sulfenylation protocol was developed to install the aromatic thioether functionality in good yield.
ISSN:1083-6160
1520-586X
DOI:10.1021/op100008m