Short and sustainable synthesis of the anticancer agent tepotinib

Abstract

Synthesis of the anticancer drug tepotinib was achieved in only 5 steps (3 steps in the longest linear sequence), with an overall yield of 75%. This compares very favorably with that used by Merck, where a linear sequence is reported requiring 8 steps to this drug in 27% overall yield. Moreover, relatively high amounts of precious metal catalyst (i.e., Pd) are needed, all reactions being carried out in toxic solvents. By contrast, a new and greener approach is now available that not only is far more efficient, but also, uses ppm level quantities of Pd and an aqueous medium for the two key Suzuki–Miyaura couplings.