A continuous flow ozonolysis method combined with a multi-step flow sequence is developed for the synthesis of the drug ivacaftor for the first time. Safe ozonolysis, a continuous flow quadruple reaction to construct a quinolone scaffold, and inline extraction followed by continuous phase separation are the key features of the present work. The feasibility of using a continuous mixed flow reactor, commonly referred to as a continuous stirred tank reactor (CSTR), is also investigated for the relatively slow reaction step. The current integrated multi-step flow synthesis can produce 7.2 g of the drug ivacaftor per day on a laboratory scale, which is sufficient to treat 50 patients per day. The present route can also be used as a general route for the synthesis of other related drugs such as quinolone antibiotics.

中文翻译：

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囊性纤维化药物依伐卡托的多步连续流合成†

首次开发了一种连续流臭氧分解方法与多步流序相结合的方法，用于合成药物依维卡托。安全的臭氧分解，连续流动的四重反应以构建喹诺酮支架，在线提取后进行连续相分离是本研究的关键特征。对于相对较慢的反应步骤，也研究了使用连续混合流反应器（通常称为连续搅拌釜反应器（CSTR））的可行性。当前的集成多步流合成每天可在实验室规模上生产7.2 g的药物依伐卡托，每天足以治疗50名患者。本途径也可以用作合成其他相关药物如喹诺酮类抗生素的一般途径。