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.

中文翻译：

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合成2-氧丙烷硫代酰胺用于制造拉那贝司他：控制，稳健性和操作改进的新途径

以市售的2，2-二乙氧基丙腈为原料，描述了一种新的合成2-氧代丙烷硫酰胺的方法，该化合物是合成拉那贝司他的关键中间体（AZD3293 / LY3314814）。与以前的路线相反，这项工作具有几个优点。例如，原材料更易于制造和处理，不再需要将剧毒的硫化氢气体用作试剂，并且原位FTIR光谱监控提供了制造控制和坚固性。另外，该途径借助可分离的结晶中间体提供了一个保留点和一个控制点，这又提供了在下游合成中明显的改进的质量。进行了广泛的实验设计分析，以了解多因素相互依赖性，建立模型，可视化因素关系，