Developing an atroposelective dynamic kinetic resolution of MRTX1719 by resolving incompatible chemical operations
Developing an atroposelective dynamic kinetic resolution of MRTX1719 by resolving incompatible chemical operations
复制标题
DOI：
10.1039/d2cc03627d
复制
发表时间：
2022-08-24
影响因子：
4.9
通讯作者：
Snead, David R.
中科院分区：
文献类型：
--
作者：
Achmatowicz, Michal M.;Chen, Cheng-yi;Snead, David R.
通过连续处理纠正结晶和差向异构化之间的不相容性，开发了一种高产率的阻转异构体拆分方案。应用于合成MRTX1719，一种密集功能化的活性药物成分（API），将产率从37%提高到87%。该方案提供了一种补充手段来获得旋转异构体，挑战当前的不对称方法，并通过减少溶剂和高级合成中间体的消耗来大大提高可持续性。
A high-yielding protocol for atropisomeric resolution was developed by rectifying incompatibilities between crystallization and epimerization via continuous processing. Application toward synthesis of MRTX1719, a densely functionalized active pharmaceutical ingredient (API), improved yield from 37% to 87%. This protocol provides a complementary means to access rotamers which challenge current asymmetric methodologies, and greatly improves sustainability by decreasing the consumption of solvent and advanced synthetic intermediates.