An efficient and practical protocol for the production of pretomanid (PA-824) via a novel synthetic strategy
| Autor: | Yuxiang Chen, Xiuqi Miao, Ming Guo, Minglin Zhu, Xin Zhai, Chen Guojun, Nan Jiang |
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| Rok vydání: | 2020 |
| Předmět: |
Green chemistry
business.industry Computer science General Chemical Engineering Industrial production Glycidol 02 engineering and technology General Chemistry 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Biochemistry Industrial and Manufacturing Engineering 0104 chemical sciences chemistry.chemical_compound chemistry Yield (chemistry) Scalability Materials Chemistry Key (cryptography) Nucleophilic substitution 0210 nano-technology Process engineering business Protocol (object-oriented programming) |
| Zdroj: | Chemical Papers. 74:3937-3945 |
| ISSN: | 1336-9075 2585-7290 |
| DOI: | 10.1007/s11696-020-01211-4 |
| Popis: | An improved, practical and efficient protocol for the production of pretomanid (1) is described. Key to this optimization was the design and development of a novel synthetic strategy, which involves the preparation of key intermediate (S)-1-(tert-butyldimethylsilyloxy)-3-(2-chloro-4-nitro-1H-imidazol-1-yl) propan-2-ol (6) from 2-chloro-4-nitroimidazole (2) and (S)-epichlorohydrin (3) through nucleophilic substitution, hydrolysis and silicon etherification reactions, followed by further O-alkylation and intramolecular cyclization to obtain pretomanid with excellent quality and yield. The new route addressed the scalability issues that existed in the reported routes, in which the explosive 2,4-dinitroimidazole, expensive (S)-1-O-(tert-butyldimethylsilyl) glycidol and laborious workups can be avoided. Furthermore, this new synthetic route provides a more efficient method to pretomanid with the characteristics of cheap and easily available raw materials, mild experimental conditions, simple operation, ‘one-pot’ procedure, which is satisfied with the requirement of green chemistry and suitable for industrial production. |
| Databáze: | OpenAIRE |
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