Modular Continuous Flow Synthesis of Imatinib and Analogues

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Process Chemistry

Background:

• Imatinib is a crucial targeted cancer therapy drug.
• Efficient synthesis of imatinib analogues is important for drug discovery.
• Continuous flow chemistry offers advantages in synthetic efficiency and scalability.

Purpose of the Study:

• To develop a modular continuous flow synthesis for imatinib and its analogues.
• To rapidly generate structurally diverse imatinib analogues.
• To establish efficient flow hydration and amidation modules.

Main Methods:

• Utilized a modular continuous flow synthesis approach.
• Employed a sequence of flow hydration and chemoselective C-N coupling.
• Used three readily available building blocks for analogue generation.
• Optimized flow setups and solvent mixtures to avoid solvent switches and in-line purifications.

Main Results:

• Successfully synthesized imatinib and a range of structurally diverse analogues.
• The continuous flow hydration and amidation modules demonstrated broad scope.
• Achieved good to excellent yields for the developed modules.
• The overall method was efficient, avoiding complex purification procedures.

Conclusions:

• A versatile and efficient modular continuous flow method for imatinib and analogue synthesis has been established.
• This approach facilitates rapid access to diverse analogues for drug discovery.
• The method's simplicity and efficiency make it suitable for broader applications in medicinal chemistry.