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Updated: Jul 12, 2026
07:06
Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
A concise and practical route to Gedatolisib via a continuous-flow Kumada coupling reaction
Jianhai Yang1,2, Jun Li1,2, Donghe Tian3
1Institute of Zhejiang University - Quzhou Quzhou Zhejiang 324000 China 0624959@zju.edu.cn nb23028@zju.edu.cn.
RSC Advances
|July 10, 2026
Summary
A new three-step synthesis for Gedatolisib, a breast cancer drug, uses continuous-flow chemistry. This safer, scalable method avoids hazardous materials and expensive catalysts, yielding high-purity drug efficiently.
Area of Science:
- Medicinal Chemistry
- Process Chemistry
- Organic Synthesis
Background:
- Gedatolisib is a dual phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor investigated for breast cancer treatment.
- Efficient and scalable synthetic routes are crucial for the clinical development and potential commercialization of novel therapeutics like Gedatolisib.
Purpose of the Study:
- To develop a practical, safe, and scalable three-step synthetic route for Gedatolisib.
- To implement continuous-flow chemistry for key transformations, enhancing efficiency and safety.
Main Methods:
- A three-step synthesis was designed, centered around a continuous-flow iron-catalyzed Kumada coupling reaction.
- The process was optimized for safety by avoiding hazardous reagents and high-boiling solvents.
- Purification was achieved through crystallization, suitable for large-scale production.
Main Results:
- The synthesis successfully produced Gedatolisib on a 100-gram scale with an overall yield of 66% and 98.9% purity.
- The continuous-flow methodology improved heat and mass transfer compared to traditional batch processes.
- The route eliminated the need for expensive noble metal catalysts and subsequent removal steps.
Conclusions:
- The developed continuous-flow synthesis offers a practical, cost-effective, and highly scalable method for Gedatolisib production.
- This approach enhances safety and environmental profiles, making it suitable for industrial manufacturing.
- The optimized process provides high-purity Gedatolisib under mild conditions.
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