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

中文翻译：

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SOS1 抑制剂 MRTX0902 的工艺开发和放大

MRTX0902 是一种新型 SOS1 抑制剂，目前正在对癌症治疗的 I 期试验进行评估。该分子含有吡啶并[3,4- d ]哒嗪核心和手性胺部分，其复杂性使其成为以公斤级规模制备以支持临床开发研究的具有挑战性的目标。开发了关键中间体 4-甲基-7-吗啉吡啶并[3,4- d ]哒嗪-1(2 H )-one 的高效且可扩展的合成方法以及大大改进的 MRTX0902 的最终方案。