Development of efficient synthetic route with flow chemistry

Axcelead Drug Discovery Partners (hereinafter referred to as Axcelead DDP) will support you in designing optimal administration of parenteral drug products from multiple points of view, combining efficacy and safety evaluation in addition to in vivo pharmacokinetic studies using a variety of routes of administration and animal species!

We establish an efficient synthetic route from an early stage to a late stage of a drug discovery research using flow chemistry, contributing to the acceleration of the project, and cost reduction!

Flow chemistry

Flow chemistry is a chemical synthetic technique in which two or more different solutions of raw materials and reagent are run through a micro flow pass under temperature and retention time (reaction time) control.

[Characteristics of the flow reactor]

Application for drug discovery research

Axcelead Drug Discovery Partners (hereinafter referred to as Axcelead DDP) has been highly successful in implementing flow chemistry with flash chemistry, nitration reactions, photoreactions, parallel synthesis, oxidation reactions, etc.

In collaboration with medicinal chemists, we design and synthesize unique and original building blocks that take advantage of the reaction properties of flow chemistry and apply them to lead compound generation/optimization studies, the construction of a new compound library, etc.

Please ask Axcelead DDP about implementing flow chemistry in drug discovery research!

Application 1: Flash chemistry

Feature 1. Establishing efficient and safe synthetic route

Feature 2. Suppression of by-products

【Problems in batch reaction】

In a batch method, treatment of an ortho-substituted halogen derivative A with BuLi was resulted in the generation of benzyne via unstable intermediate. Because of the production of various by-products arising from the high reactivity of benzyne, scale-up synthesis to several hundred gram by the original route was not practical.

【Advantage in flow chemistry】

Side reactions were successfully suppressed even at the 110 g scale-up level. Improvements in the reaction yield and productivity were achieved.
[Source] Shotaro Miura, Org.Biomol.Chem.,2019,17,8166

Application 2: Photoreaction

In a photo-flow reaction, reaction solutions are irradiated efficiently, and also discharged from the reaction system after a certain period of time and therefore, side reactions can be suppressed. We have many success examples in photo-flow chemistry, and also utilized in an efficient synthesis of the unique building blocks.

[Source] Toshiro Yamashita, Tetrahedron.,2019,75,617-623


Q:How much raw material is needed to examine the flow reaction,

A:For a single process, for example, converting a reaction in a batch method for which the conditions have already been established to a flow reaction (to avoid hazardous reactions such as nitration, nitro reduction, azidation, and azide reduction), several tens of grams of raw materials would be required. You can outsource to us for the development of synthetic routes effectively using flow reaction, including raw material synthesis.

Q:Are there any compounds unsuitable for flow chemistry?

A:Due to the use of a narrow channel in reactions, low solubility compounds or compounds generating substances that are poorly-soluble in the solvent during the reaction may cause the channel to block by crystallization.