Synthesis of 2-Oxopropanethioamide for the Manufacture of Lanabecestat: A New Route for Control, Robustness, and Operational Improvements
| Autor: | Cristina Fernandez Barrat, Phillip A. Inglesby, Brian A. Taylor, Robert L. Woodward |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
010405 organic chemistry
business.industry Computer science media_common.quotation_subject Organic Chemistry Process (computing) Process variable Raw material 010402 general chemistry 01 natural sciences 0104 chemical sciences Downstream (manufacturing) Robustness (computer science) SAFER Key (cryptography) Quality (business) Physical and Theoretical Chemistry Process engineering business media_common |
| Zdroj: | Organic Process Research & Development. 21:1404-1412 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.7b00170 |
| Popis: | A new route to 2-oxopropanethioamide, a key intermediate in the synthesis of lanabecestat (AZD3293/LY3314814), is described by employing commercially available 2,2-diethoxypropionitrile as a raw material. In contrast to the previous route, this work offers several advantages; for example, the raw material is safer to manufacture and handle, highly toxic hydrogen sulfide gas is no longer required as a reagent, and in situ FTIR spectroscopy monitoring has provided manufacturing controls and robustness. Additionally, this route offers a hold- and control-point by virtue of an isolable crystalline intermediate, which in turn provides improved quality that is evident in the downstream synthesis. An extensive design-of-experiment analysis was undertaken to understand multifactor interdependencies, build a model, visualize factor relationships, map the process parameter reaction space, identify potential process operating conditions, and predict their performance. |
| Databáze: | OpenAIRE |
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