| Autor: |
Qu, Bo, Wei, Xudong, Zeng, Xingzhong, Yang, Bing-Shiou, Desrosiers, Jean-Nicolas, Savoie, Jolaine, Wang, Jun, Marsini, Maurice A., Li, Zhibin, Haddad, Nizar, Lorenz, Jon C., Tielmann, Patrick, Maier, Nora, Song, Jinhua J., Senanayake, Chris H. |
| Zdroj: |
Organic Process Research & Development; March 2022, Vol. 26 Issue: 3 p963-975, 13p |
| Abstrakt: |
An economical and practical manufacturing process for an 11β-HSD-1 inhibitor is reported. The key feature of the synthesis is the identification of a unique and effective MeO-BoQPhos ligand for the Ir-catalyzed asymmetric hydrogenation of a fused tricyclic indenopyridinium salt. It is the first highly reactive chiral P,N ligand system to be utilized in asymmetric pyridine reduction. The enantioenriched indanopiperidine was produced with a low catalyst loading of 1000 ppm [Ir(COD)Cl]2. The challenges and solutions for final active pharmaceutical ingredient (API) physicochemical properties are also described. This asymmetric synthesis of the API was accomplished in 38% overall yield with >99.8% ee and >99.5 area % purity. This overall process results in a much shorter production cycle and significant waste reduction on the manufacturing scale. |
| Databáze: |
Supplemental Index |
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