The Discovery and Development of a Safe, Practical Synthesis of ABT-869
The Discovery and Development of a Safe, Practical Synthesis of ABT-869
复制标题
DOI：
10.1021/op900208y
复制
发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Wang, Zhe
中科院分区：
文献类型：
--
作者：
Kruger, Albert W.;Rozema, Michael J.;Wang, Zhe
据报道，ABT-869 的两条化学路线的发现、开发和实施。简要描述了第一代杂环形成和铃木耦合的优化。第二代合成的主要特点包括通过利用无机碱提高放热分解的起始温度来开发安全的肼缩合反应。详细讨论了第二代铃木反应，最终使用氧气监测器作为 PAT，以最大限度地提高规模重现性。
The discovery, development and implementation of two chemical routes to ABT-869 is reported. Optimization of the first-generation heterocycle formation and Suzuki coupling is briefly described. Key features of the second-generation synthesis include the development of a safe hydrazine condensation by utilizing an inorganic base to increase the onset temperature of exothermic decomposition. The second-generation Suzuki reaction is discussed in detail, culminating in the use of an oxygen monitor as a PAT to maximize reproducibility on scale.