A Scaleable Synthesis of BAY 43-9006: A Potent Raf Kinase Inhibitor for the Treatment of Cancer

Abstract

Urea 3 (BAY 43-9006), a potent Raf kinase inhibitor, was prepared in four steps with an overall yield of 63%. Significant process research enabled isolation of each intermediate and target without chromatographic purification, and overall yield increases >50% were observed compared to those from previous methods. This report focuses on improved synthetic strategies for production of scaled quantities of 3 for preclinical, toxicological studies. These improvements may be useful to assemble other urea targets as potential therapeutic agents to combat cancer.