Flow parallel synthesizer for multiplex synthesis of aryl diazonium libraries via efficient parameter screening

Area of Science:

• Chemical Synthesis
• Medicinal Chemistry
• Process Chemistry

Background:

• Miniaturized flow platforms offer efficient synthesis of drug and lead molecules.
• Current continuous flow technologies lack the capability for simultaneous multi-reaction synthesis.

Purpose of the Study:

• To develop a metal-based flow parallel synthesizer for multiplex compound library synthesis.
• To enable efficient screening of reaction parameters for optimizing synthetic methodologies.

Main Methods:

• A miniaturized synthesizer with a built-in flow distributor and multiple microreactors was employed.
• Diazonium-based reactions were used as a test case, distributing reagents to 16 capillaries.
• Multiplex screening of 96 reaction variables (time, concentration, product type) was performed.

Main Results:

• The synthesizer successfully executed multiple reaction types in parallel, including photochemistry.
• Various C-C, C-N, C-X, and C-S bonds were formed through multiplex synthesis.
• Optimization of 24 different aryl diazonium chemistries was achieved.

Conclusions:

• The developed flow parallel synthesizer facilitates rapid exploration of synthetic routes and optimization.
• This technology can significantly accelerate the discovery and development of new drug molecules.
• The platform's ability to perform diverse reactions in parallel is transformative for chemical synthesis.