Mild and efficient DBU-catalyzed amidation of cyanoacetates

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Process Chemistry

Background:

• Direct amidation of cyanoacetates is challenging, often requiring cyanoacetic acid activation or high temperatures.
• Developing mild and efficient synthetic routes is crucial for pharmaceutical development.

Purpose of the Study:

• To present a novel, mild, and high-yielding protocol for the direct amidation of alkyl cyanoacetates.
• To demonstrate the practicality of this method for large-scale synthesis.

Main Methods:

• Utilized 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) as a catalyst for direct amidation.
• Applied the protocol to the synthesis of specific pharmaceutical intermediates.

Main Results:

• Achieved direct amidation of alkyl cyanoacetates under mild conditions.
• Demonstrated high yields and practicality of the developed method.
• Successfully applied the protocol to the large-scale synthesis of CP-690,550-10.

Conclusions:

• The presented DBU-mediated amidation protocol offers a practical and efficient alternative to existing methods.
• This method simplifies the synthesis of valuable cyanoacetate derivatives, including pharmaceutical compounds for autoimmune diseases.