Synthesis of 1-(tert-Butyl) 4-Methyl (1R,2S,4R)-2-Methylcyclohexane-1,4-dicarboxylate from Hagemann’s tert-Butyl Ester for an Improved Synthesis of BMS-986251
| العنوان: | Synthesis of 1-(tert-Butyl) 4-Methyl (1R,2S,4R)-2-Methylcyclohexane-1,4-dicarboxylate from Hagemann’s tert-Butyl Ester for an Improved Synthesis of BMS-986251 |
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| المؤلفون: | Dauh-Rurng Wu, Joseph Pawluczyk, Robert J. Cherney, Joseph A. Tino, Shiuhang Yip, T. G. Murali Dhar, James Kempson, Jianqing Li, Darpandeep Aulakh, Amy A. Sarjeant, Daniel Smith, Arvind Mathur, Cornelius Lyndon A M, Subramaniam Krishnananthan |
| المصدر: | The Journal of Organic Chemistry. 85:10988-10993 |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Tert butyl, 010405 organic chemistry, Chemistry, Organic Chemistry, Synthon, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Enol, 0104 chemical sciences, chemistry.chemical_compound, Inverse agonist, Stereoselectivity, Methylcyclohexane, Trifluoromethanesulfonate, Derivative (chemistry) |
| الوصف: | We describe an efficient synthetic route to differentially protected diester, 1-(tert-butyl) 4-methyl (1R,2S,4R)-2-methylcyclohexane-1,4-dicarboxylate (+)-1, via palladium-catalyzed methoxycarbonylation of an enol triflate derived from a Hagemann's ester derivative followed by a stereoselective Crabtree hydrogenation. Diester 1 is a novel chiral synthon useful in drug discovery and was instrumental in the generation of useful SAR during a RORγt inverse agonist program. In addition, we describe a second-generation synthesis of the clinical candidate BMS-986251, using diester 1 as a critical component. |
| تدمد: | 1520-6904 0022-3263 |
| DOI: | 10.1021/acs.joc.0c01169 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::8fba5ca413d795699a30093fecc6e060 https://doi.org/10.1021/acs.joc.0c01169 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi...........8fba5ca413d795699a30093fecc6e060 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15206904 00223263 |
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| DOI: | 10.1021/acs.joc.0c01169 |