PROCESS CHEMISTRY
Flow chemistry advanced in industry Lilly chemists capitalized on continuous chemical manufacturing to make a chemotherapy drug candidate
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by regulatory agencies for drug produclow chemistry has been steadily tion (Science 2017, DOI: 10.1126/science. gaining ground in academia in reaan0745). cent years, and in 2017 the continuKevin P. Cole, the report’s lead ous chemical synthesis method—in N author, explained in June that which tubes HN CN the group decided to go for H3C and T-junction mixers N O replace the flasks and O a flow approach because N Lilly needed only 24 kg stir bars used for batch reN H O– of the drug candidate. actions—managed to make H2O O OH Making prexasertib inroads in the pharmaceuin batch equipment tical industry. One mileNH3+ stone: Chemists at Eli Prexasertib monolactate monohydrate would have required an extensive cleanup Lilly & Co. used continafterward because the compound is pouous-flow chemistry as a safer, faster, and A walk-in fume hood contains newly tent and cytotoxic, so any residue could cheaper way to make the chemotherapy designed continuous-flow equipment at Eli potentially contaminate future reactions. drug candidate prexasertib monolactate Lilly’s facility in Kinsale, Ireland. The small flow setup the team used could monohydrate. Flow chemistry was popular elsebe dedicated to making this single comThe Lilly team set up eight continuous where this year. Flow chemistry company process steps to make the compound. One pound and then discarded, if necessary, Snapdragon partnered step used hydrazine, a O with Pfizer to prepare component of rocket H O N O Li H H the highly reactive fuel, which would have H n-Hexyllithium O reagent allenyllithium been too dangerous to O N Chiral zinc complex H en route to making an use in a batch process. H H OH important drug interBut perhaps the most Allene Allenyllithium Chiral homopropargyl 𝛍-amino alcohol mediate. Snapdragon notable part of this synat no great cost, Cole said. The success of also formed a pact with Johnson Matthey, thesis is that the Lilly chemists linked the a leading supplier of bulk pharmaceutical using flow to make prexasertib prompted final stages in the continuous manufacchemicals, to collaborate on flow chemLilly to build a continuous-flow facilituring process to quality-control systems istry for drug manufacturing.—BETHANY ty in Kinsale, Ireland, which opened in to achieve current Good Manufacturing October. Practices (cGMPs) standards required HALFORD
CR E DI T: E L I L I L LY & CO.
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DECEMBER 11/18, 2017 | CEN.ACS.ORG | C&EN
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