Development and Manufacture of a Curtius Rearrangement Using Continuous Flow towards the Large-Scale Manufacture of AZD7648
Development and Manufacture of a Curtius Rearrangement Using Continuous Flow towards the Large-Scale Manufacture of AZD7648
复制标题
使用连续流开发和制造 Curtius 重排以大规模制造 AZD7648
DOI：
10.1021/acs.oprd.2c00316
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Steven Knight
中科院分区：
文献类型：
--
作者：
Carl J. Mallia;Niall G McCreanor;Danny H. Legg;Craig R. Stewart;Sarah Coppock;I. Ashworth;Joël Le Bars;Adam Clarke;Graeme Clemens;H. Fisk;Helen Benson;Samantha Oke;Trevor Churchill;Marcus A. Hoyle;L. Timms;K. Vare;Martin Sims;Steven Knight
由于设备的进步和生产设施的可用性，流动化学已更频繁地用于药物的开发和生产。这一重要的制造工具使以前低效、危险或不可行的化学品批量生产成为可能。本文描述的是如何使用连续流来克服关于批量处理危险材料的问题。所述生产步骤是使用二苯基磷酰叠氮化物（DPPA）作为叠氮化物前体在高温下形成嘌呤酮的Curtius反应，并进行在线红外监测。
Flow chemistry has been more frequently used in the development and manufacture of pharmaceuticals due to the progression of equipment and the availability of manufacturing facilities. This important tool for manufacture enables chemistries which were previously inefficient, hazardous, or not viable on scale in batch. Described herein is how continuous flow has been used to overcome issues with respect to the handling of hazardous materials in batch. The manufacturing step described is a Curtius reaction using diphenylphosphoryl azide (DPPA) as the azide precursor in the formation of a purinone at high temperatures with inline infrared monitoring.