Palbociclib Commercial Manufacturing Process Development. Part I: Control of Regioselectivity in a Grignard-Mediated SNAr Coupling
| Autor: | Karen Sutherland, Fangming Kong, Nathan D. Ide, Hahdi H. Perfect, John Draper, Kyle R. Leeman, Mark Olivier, Ke Wang, Jon Blunt, Shengquan Duan, Mark T. Maloney, David Place, Maria M. O’Sullivan, Denis Lynch, Wiglesworth Kristin, Marie McAuliffe |
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| Rok vydání: | 2016 |
| Předmět: |
010405 organic chemistry
Chemistry Manufacturing process Organic Chemistry Regioselectivity Palbociclib 010402 general chemistry 01 natural sciences Combinatorial chemistry 0104 chemical sciences Coupling (computer programming) Nucleophilic aromatic substitution Organic chemistry Physical and Theoretical Chemistry |
| Zdroj: | Organic Process Research & Development. 20:1191-1202 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.6b00070 |
| Popis: | This is the first in a series of three papers describing commercial manufacturing process development for palbociclib (1). This manuscript focuses on the SNAr coupling between aminopyridine 3 and chloropyrimidine 7. The regioselectivity of the SNAr coupling was studied from a synthetic and mechanistic perspective. Grignard bases were identified as the preferred class of bases for this reaction, allowing for a simplified process and reduced usage factor for aminopyridine 3. The development of this SNAr reaction into a scalable commercial manufacturing process is also described. |
| Databáze: | OpenAIRE |
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