T3P®-Assisted cascade synthesis of N-acyl α-cyanoamines, cyanoaryl amides and N-acyl cyanoarylamines: Application in making three pharmaceutically important molecules

Abstract

Organic compounds possessing N-acyl α-cyanoamine function shows numerous pharmaceutical and medicinal properties, however, their synthesis require multiple steps. This article describes a novel and sustainable one-pot construction of N-acyl α-cyanoamines from α-amino amides and acids via propanephosphonic acid anhydride (T3P®)-assisted cascade strategy. A variety of chiral α-amino amides were conveniently transformed to N-acyl α-cyanoamine derivatives (15) by reacting with carboxylic acids using current protocol. The products are formed in 81–94% in 12 h at room temperature. Additionally, this method was also extended to the synthesis of cyanoaryl amides (18) (from 4-((aminooxy)carbonyl)benzoic acid and primary/secondary amines) and N-acyl cyanoarylamines (20) (from 3-aminobenzamide and carboxylic acids) with 83–95% yields in 2 h at 70 °C. The developed strategy has also been utilized successfully for the synthesis of DPP-4 inhibition agent, 2, intermediate, 4 of SphK1 inhibitor, and clinical agent of COVID-19, 10. These procedures are step-as well as pot-economic, which saves the reagents, solvents and separation agents required for the multiple steps that are associated with the reported routes.