A novel and efficient continuous-flow route to prepare trifluoromethylated N-fused heterocycles for drug discovery and pharmaceutical manufacturing

Amini-Rentsch, Lara (Idorsia Pharmaceuticals Ltd., Chemistry Technologies & Lead Discovery, Department of Drug Discovery Chemistry, Allschwil, Switzerland ; School of Engineering and Architecture (HEIA-FR), HES-SO // University of Applied Sciences Western Switzerland) ; Vanoli, Ennio (School of Engineering and Architecture (HEIA-FR), HES-SO // University of Applied Sciences Western Switzerland) ; Richard-Bildstein, Sylvia (Idorsia Pharmaceuticals Ltd., Chemistry Technologies & Lead Discovery, Department of Drug Discovery Chemistry, Allschwil, Switzerland) ; Marti, Roger (School of Engineering and Architecture (HEIA-FR), HES-SO // University of Applied Sciences Western Switzerland) ; Vilé, Gianvito (Idorsia Pharmaceuticals Ltd., Chemistry Technologies & Lead Discovery, Department of Drug Discovery Chemistry, Allschwil, Switzerland)

Continuous-flow processing has become one of the fastest-growing research areas in chemistry in the last 10 years. Herein we disclose an automated and scalable continuous-flow route for the quick introduction of trifluoromethyl groups on a variety of heterocycles, with application in drug discovery and manufacturing. This involves the direct alkylation-cyclization of amines in the presence of trifluoroacetic acid or anhydride, cheap and readily available CF3-containing building blocks. Compared to traditional batch reactions involving an intermediate purification step, the continuous-flow reactions occurred quickly and at mild conditions, with high yield and broad functional-group tolerance. The practical utility of the method was demonstrated by a gram-scale synthesis and by the estimation of modern green metrics.


Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEIA-FR
Institute:
ChemTech - Institut des technologies chimiques
Subject(s):
Ingénierie
Date:
2019-05
Pagination:
8 p.
Published in:
Industrial & Engineering Chemistry Research (I & EC research)
Numeration (vol. no.):
2019, vol. 58, no. 24, pp. 10164-10171
DOI:
ISSN:
0888-5885
Appears in Collection:



 Record created 2019-06-25, last modified 2019-06-25

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