Multi-step continuous flow synthesis of the cystic fibrosis medicine ivacaftor

TitleMulti-step continuous flow synthesis of the cystic fibrosis medicine ivacaftor
Publication TypeJournal Article
Year of Publication2018
AuthorsVasudevan, N, Sharma, MK, D. Reddy, S, Kulkarni, AA
JournalReaction Chemistry & Engineering
Volume3
Issue4
Pagination520-526
Date PublishedAUG
ISSN2058-9883
Abstract

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.

DOI10.1039/c8re00025e
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)4.641
Divison category: 
Chemical Engineering & Process Development
Organic Chemistry

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