Verubecestat is an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) that is currently under clinical evaluation for the treatment of prodromal Alzheimer’s disease. This article describes the characterization of a co-crystal composed of a HBr salt of verubecestat and a HBr salt of a reaction intermediate as the components. This unique co-crystal was formed during production of a multikilogram batch of verubecestat. The impact of this observation is discussed, followed by the description of a modified procedure that served to prevent the formation of this highly unusual crystalline material.

中文翻译：

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BACE1抑制剂Verubecestat和反应中间体的独特共晶体的表征：对商业化生产工艺发展的启示

Verubecestat是一种β-位淀粉样蛋白前体蛋白裂解酶1（BACE1）的抑制剂，目前正处于临床评估中，以治疗前驱性阿尔茨海默氏病。本文描述了由Verubecestat的HBr盐和反应中间体的HBr盐作为组分组成的共晶体的表征。这种独特的共晶体是在生产多千克批次的verubecestat的过程中形成的。讨论了该观察结果的影响，然后描述了用于防止这种高度不同寻常的晶体材料形成的改进程序。