Early Development Scale-Up of a Structurally-Challenging 5-Lipoxygenase Activating Protein (FLAP) Inhibitor
| Autor: | Zhidong Chen, Carl A. Busacca, Shengli Ma, Xingzhong Zeng, Peter Allen Nemoto, Paige E. Mahaney, Jason A. Mulder, Chris H. Senanayake, Jun Wang, Nitinchandra D. Patel, Zhibin Li, Todd Bosanac, Daniel R. Fandrick, Jean-Nicolas Desrosiers, Heewon Lee, Sonia Rodriguez, Jon C. Lorenz, Nathan K. Yee, Joe Gao, Nelu Grinberg, Hidenori Takahashi, Alessandra Bartolozzi, Jinhua J. Song, Keith R. Fandrick |
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| Rok vydání: | 2017 |
| Předmět: |
Chromatography
biology 010405 organic chemistry Chemistry Organic Chemistry Structural component 010402 general chemistry 01 natural sciences Combinatorial chemistry 0104 chemical sciences Supercritical fluid chromatography biology.protein Physical and Theoretical Chemistry 5-lipoxygenase-activating protein |
| Zdroj: | Organic Process Research & Development. 21:1427-1434 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.7b00202 |
| Popis: | A practical and efficient synthesis of the FLAP inhibitor 1 was developed addressing multiple scale-up and safety concerns posed by the established synthesis and utilized a resolution strategy (replacing supercritical fluid chromatography (SFC) separation) for expedient access to the key structural component of 1: the challenging chiral quaternary center. Also highlighted are in situ IR monitoring, condensation to form the 1,2,4-oxadiazole ring, and an efficient Suzuki-Miyaura coupling. |
| Databáze: | OpenAIRE |
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