New and Convergent Synthesis of Osimertinib

New and convergent synthetic route of osimertinib is described on a dozen of grams scale. A key cyclization of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)guanidine and 3-(dimethylamino)-1-(1-methyl-1H-indol-3-yl)prop-2-en-1-one is adopted to give the 4-(1H-indol-3-yl)-N-phenylpyrimidin-2-amine structure. Osimertinib is prepared in 40.4% yield over six steps and 99.1% purity (HPLC). Purification methods of the intermediates involved in the route are also given.