A Practical Synthesis of the RARγ Agonist, BMS-270394

A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARγ) agonist, is reported. The synthesis includes an enantioselective reduction of α-ketoacid 4 to the corresponding chiral α-hydroxy acid 7 using a NaBH4/l-tartaric acid mixture and a novel coupling between 7 and an electron-de...

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Bibliographic Details
Published in:Organic process research & development 2002-09, Vol.6 (5), p.632-636
Main Authors: Chidambaram, Ramakrishnan, Kant, Joydeep, Zhu, Jason, Lajeunesse, Jean, Sirard, Pierre, Ermann, Peter, Schierling, Peter, Lee, Peter, Kronenthal, David
Format: Article
Language:English
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Summary:A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARγ) agonist, is reported. The synthesis includes an enantioselective reduction of α-ketoacid 4 to the corresponding chiral α-hydroxy acid 7 using a NaBH4/l-tartaric acid mixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative 15 to form chiral α-hydroxy amide 16. The synthesis was completed by a racemization-free hydrolysis of 16 to the corresponding α-hydroxy amidoacid 1 using KOSiMe3 in acetonitrile.
ISSN:1083-6160
1520-586X
DOI:10.1021/op0202134