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Open AccessArticle

Optimisation by Design of Experiment of Benzimidazol-2-One Synthesis under Flow Conditions

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy
Current affiliation: Novartis Pharma AG, CH-4002 Basel, Switzerland
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06560 Ankara, Turkey
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2019, 24(13), 2447;
Received: 30 May 2019 / Revised: 27 June 2019 / Accepted: 28 June 2019 / Published: 3 July 2019
(This article belongs to the Special Issue Enabling Chemical Technologies in Medicinal Chemistry)
A novel flow-based approach for the preparation of benzimidazol-2-one (1) scaffold by the 1,1′-carbonyldiimidazole (CDI)-promoted cyclocarbonylation of o-phenylenediamine (2) is reported. Starting from a preliminary batch screening, the model reaction was successfully translated under flow conditions and optimised by means of design of experiment (DoE). The method allowed the efficient preparation of this privileged scaffold and to set up a general protocol for the multigram-scale preparation in high yield, purity, and productivity, and was successfully applied for the multigram flow synthesis of N-(2-chlorobenzyl)-5-cyano-benzimidazol-2-one, which is a key synthon for hit-to-lead explorations in our anti-inflammatory drug discovery program. View Full-Text
Keywords: flow chemistry; statistical experimental design; benzimidazol-2-one flow chemistry; statistical experimental design; benzimidazol-2-one
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MDPI and ACS Style

Mostarda, S.; Gür Maz, T.; Piccinno, A.; Cerra, B.; Banoglu, E. Optimisation by Design of Experiment of Benzimidazol-2-One Synthesis under Flow Conditions. Molecules 2019, 24, 2447.

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