Process Development toward a Pro-Drug of Buprenorphine
| العنوان: | Process Development toward a Pro-Drug of Buprenorphine |
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| المؤلفون: | Robin Marshall, Catherine Smyth, J. Alf Davis, Alasdair Garnett, Julian Scott Northen, John S. Carey, Stephen J. Byard, Urvish Pandya, Stephen John Martin, Antonio Codina, Gary Patrick Reid, John Mykytiuk, Sophie L. Berrell, Katherine Filer, Lesa Watson |
| المصدر: | Organic Process Research & Development. 23:762-770 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Conformational change, Differential scanning calorimetry, Materials science, Impurity, Adipate, Organic Chemistry, Recrystallization (metallurgy), Nuclear magnetic resonance spectroscopy, Physical and Theoretical Chemistry, Combinatorial chemistry, Endothermic process, Powder diffraction |
| الوصف: | This paper describes the process development conducted toward the multi-kilogram synthesis of a hemiadipic acid pro-drug of buprenorphine. The major challenges were to control the levels of the dibuprenorphine monoadipate impurity and to improve the robustness of the final recrystallization. Modification of the reaction conditions limited the levels of the impurity formed during the reaction, and an additional point of control was introduced, a reslurry with dichloromethane. The solid-state properties of the pro-drug were fully investigated, and extensive polymorph screening was undertaken. An unusual low-temperature endothermic event was observed in the differential scanning calorimetry thermogram. This low-temperature event was further investigated using variable-temperature X-ray powder diffraction and variable-temperature solid-state nuclear magnetic resonance spectroscopy. It was concluded that this event was likely to be associated with a reversible, minor conformational change of the adipate side c... |
| تدمد: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.9b00025 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::878ee5f6f614c4c5a97ffeffdec68649 https://doi.org/10.1021/acs.oprd.9b00025 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi...........878ee5f6f614c4c5a97ffeffdec68649 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1520586X 10836160 |
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| DOI: | 10.1021/acs.oprd.9b00025 |