01449nas a2200181   4500008004100000022001400041245008300055210006900138260000800207300001200215490000600227520083400233100001801067700002701085700002101112700002301133856011101156       2018                        eng d  a2058-988300aMulti-step continuous flow synthesis of the cystic fibrosis medicine ivacaftor0 aMultistep continuous flow synthesis of the cystic fibrosis medic  cAUG  a520-5260 v33 a<p>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.</p>1 aVasudevan, N.1 aSharma, Mrityunjay, K.1 aReddy, Srinivasa1 aKulkarni, Amol, A.  uhttps://library.ncl.res.in/content/multi-step-continuous-flow-synthesis-cystic-fibrosis-medicine-ivacaftor