Approaches to a Scaleable Synthesis of CH8757: A Potent Inhibitor of Matrix Metalloproteinases

Abstract

The synthesis of the matrix metalloproteinase (MMP) inhibitor CH8757 is described. The discovery route has been modified to incorporate a three-stage one-pot sequence using α,α,α-trifluorotoluene as solvent. The formation of the hydroxamic acid using oxalyl chloride is catalysed by DBU, thus avoiding the use of DMF, which may form the highly toxic byproduct, dimethylcarbamoyl chloride.