| Autor: |
Akin, Anne, Barrila, Mark T., Brandt, Thomas A., Dechert-Schmitt, Anne-Marie R., Dube, Pascal, Ford, David D., Kamlet, Adam S., Limberakis, Chris, Pearsall, Andrew, Piotrowski, David W., Quinn, Brian, Rothstein, Sarah, Salan, Jerry, Wei, Liuqing, Xiao, Jun |
| Zdroj: |
Organic Process Research & Development; 20240101, Issue: Preprints |
| Abstrakt: |
The synthesis of multigram quantities of small molecule PCSK9 inhibitor (R,S)-3is described. The route features a safe, multikilogram method to prepare 5-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2H-tetrazole (10). A three-component dynamic kinetic resolution between tetrazole 10, acetaldehyde, and isobutyric anhydride was catalyzed by a chiral DMAP catalyst to afford enantiomerically enriched hemiaminal ester (S)-12on multikilogram scale. Magnesiation, transmetalation, and Negishi coupling provided access to Boc-intermediate (R,S)-13, which was deprotected to provide (R,S)-3in multigram quantities. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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