Kinetic and mechanistic insight into the thermodynamic degradation of saxagliptin
The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer (Figure presented).
Jones, G. Scott,Savage, Scott A.,Ivy, Sabrina,Benitez, Patrick L.,Ramirez, Antonio
Get Best Price for1350800-77-91H-Cyclopropa[4,5]pyrrolo[1,2-a]pyrazine-3,6-dione, hexahydro-4-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-, (1aS,4S,6aR,7aS)-