The starting material used in the discovery team route, methyl 5-bromo-2-methoxyisonicotinate 1, was not commercially available on multi-kilogram scale and had to be custom-synthesized in several steps with a lead time greater than 8 weeks. While acceptable for the first kilogram delivery, this proved challenging for future scale-up campaigns and therefore needed to be addressed. In addition, the key intermediate, 1,7-dichloro-4-methylpyrido pyridazine 6, was susceptible to hydrolysis upon storage under normal humidity level; therefore, it was flagged as a potential issue in the long run. Additionally, the first SNAr towards intermediate 7 was reported to give only a moderate yield 3 of 43% due to inherent selectivity issues, and was challenging to reproduce with the desired purity without resorting to preparative HPLC. Lastly, the order of the two final SNAr reactions leading to MRTX0902 was suboptimal as the more expensive chiral benzylic amine was introduced before the inexpensive morpholine. Reversing the order of steps would directly reduce the cost of the overall synthesis.