Lehmann, Hansjoerg, Knoepfel, Thomas and Ruppen, Thomas (2022) Scale-up of Diazonium Salts and Azides in a Three-step Continuous Flow Sequence. Organic Process Research & Development.

Abstract

Rapid synthesis and scale-up of active molecules to support the development process of new drug candidates is key in the pharmaceutical industry. Herein we describe the development of a scalable continuous flow procedure for two key steps in the synthesis of 2H-indazoles which were identified as highly potent and selective TLR7 and TLR8 antagonists. Transformation of hazardous azide chemistries from batch to continuous flow mode helped to mitigate and limit the risks associated with the handling of large amounts of hazardous reagents and intermediates in batch. In a two-step approach, we first screened and optimized reaction parameter for an azidation and cyclization reaction using a commercial research scale plug-flow reactor. In a second step we demonstrated the robustness and scalability of both reactions which finally enabled us to rapidly prepare and deliver the required amount of material in high quality.

Item Type:	Article
Keywords:	continuous flow chemistry, hazardous chemistry, scale-up, azides, cyclization, 2H-indazoles
Date Deposited:	13 Apr 2022 00:45
Last Modified:	13 Apr 2022 00:45
URI:	https://oak.novartis.com/id/eprint/46571