A Practical Synthesis of the RAR Agonist, BMS-270394
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- 作者：Ramakrishnan Chidambaram ; Joydeep Kant ; Jason Zhu ; Jean Lajeunesse ; Pierre Sirard ; Peter Ermann ; Peter Schierling ; Peter Lee ; and David Kronenthal
- 刊名：Organic Process Research & Development
- 出版年：2002
- 出版时间：September 2002
- 年：2002
- 卷：6
- 期：5
- 页码：632 - 636
- 全文大小：77K
- 年卷期：v.6,no.5(September 2002)
- ISSN：1520-586X
文摘
A novel synthesis of 1 (BMS-270394), a nuclear retinoic acidreceptor (RAR
) agonist, is reported. The synthesis includesan enantioselective reduction of 
-ketoacid 4 to the corresponding chiral -hydroxy acid 7 using a NaBH4/L-tartaric acidmixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative15 to form chiral -hydroxy amide 16. The synthesis wascompleted by a racemization-free hydrolysis of 16 to thecorresponding -hydroxy amidoacid 1 using KOSiMe3 inacetonitrile.
) agonist, is reported. The synthesis includesan enantioselective reduction of -ketoacid 4 to the corresponding chiral -hydroxy acid 7 using a NaBH4/L-tartaric acidmixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative15 to form chiral -hydroxy amide 16. The synthesis wascompleted by a racemization-free hydrolysis of 16 to thecorresponding -hydroxy amidoacid 1 using KOSiMe3 inacetonitrile.