Process Development and Scale-Up of the SOS1 Inhibitor MRTX0902

MRTX0902, a novel SOS1 inhibitor, is currently being evaluated in phase I trials for the treatment of cancer. The complexity of the molecule containing a pyrido[3,4-d]pyridazine core and a chiral amine moiety makes it a challenging target to prepare on multi-kilogram scale to support clinical development studies. An efficient and scalable synthesis to the key intermediate, 4-methyl-7-morpholinopyrido[3,4-d]pyridazin-1(2H)-one and a much improved end-game to MRTX0902 was developed.