Building on this first successful delivery for GLP toxicology studies, our next challenge was to address the commercial unavailability of the starting material used (compound 1). Our second major challenge was to eliminate the need of the expensive Buchwald Pd precatalyst (P(tBu)3Pd-G2) used in the first step of the discovery synthesis. 5 The use of palladium very early in the synthesis has a direct impact on the overall cost effectiveness of the synthetic approach so the design of a new route and the choice of a readily available starting material were fundamental considerations in the development work for MRTX0902 fumarate.