Adventures in Atropisomerism: Development of a Robust, Diastereoselective, Lithium-Catalyzed Atropisomer-Forming Active Pharmaceutical Ingredient Step
| العنوان: | Adventures in Atropisomerism: Development of a Robust, Diastereoselective, Lithium-Catalyzed Atropisomer-Forming Active Pharmaceutical Ingredient Step |
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| المؤلفون: | Federico Lora Gonzalez, Steven R. Wisniewski, Brendan Mack, Ronald Carrasquillo-Flores, Maxime Soumeillant, Matthew Casey, Thomas M. Razler, Antonio Ramirez |
| المصدر: | Organic Process Research & Development. 22:1426-1431 |
| بيانات النشر: | American Chemical Society (ACS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Active ingredient, Atropisomer, 010405 organic chemistry, Organic Chemistry, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, law.invention, Catalysis, chemistry, law, Lithium, Physical and Theoretical Chemistry, Crystallization, Counterion |
| الوصف: | The final step in the route to BMS-986142, a reversible inhibitor of the BTK enzyme, involves the diastereoselective construction of a chiral axis during the base-mediated cyclization of the quinazolinedione fragment. Optimization of the reaction to minimize formation of the undesired atropisomer led to the discovery that the amount of base and nature of the counterion play a vital role in the diastereoselectivity of the reaction. The highest diastereoselectivities were observed with a catalytic amount of LiOt-Bu. Development of a crystallization to selectively purge the undesired atropisomer is reported. Interestingly, ripening of the crystalline API was observed and further investigated, leading to a significant increase in the purity of the active pharmaceutical ingredient. |
| تدمد: | 1520-586X 1083-6160 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::117e95619df4dbcc06b6518add2a6956 https://doi.org/10.1021/acs.oprd.8b00246 |
| رقم الأكسشن: | edsair.doi...........117e95619df4dbcc06b6518add2a6956 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 1520586X 10836160 |
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