抄録
This manuscript details the process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines and a thermochemically safe synthesis of a 1,2,4-aminotriazole fragment. A key feature of the synthesis is the use and optimization of a modified Julia-Kocienski olefination reaction. Specifically, we report an unprecedented dependence of the product olefin geometry on reaction temperature, where an E:Z ratio as high as 200:1 can be obtained. Initial insights into the mechanistic rationale for this observation are also provided. Finally, a purity upgrade sequence via an intermediate crystalline form is highlighted as a method of controlling the final API quality.
本文言語 | English |
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ページ(範囲) | 441-458 |
ページ数 | 18 |
ジャーナル | Organic Process Research and Development |
巻 | 14 |
号 | 2 |
DOI | |
出版ステータス | Published - 2010 3月 19 |
外部発表 | はい |
ASJC Scopus subject areas
- 物理化学および理論化学
- 有機化学