(S)-N-(8-((2-Amino-2,4-dimethylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-yl)acetamide (1) is a potent adaptor-associated kinase 1 inhibitor, which may have the potential to treat neuropathic pain and other neurological disorders including schizophrenia, Parkinson’s disease, bipolar disorder, and Alzheimer’s disease. For preclinical studies, a substantial amount of high-quality material was required. The original discovery route for the preparation of this compound suffered from scale-up issues that included a very low-yielding C–O coupling step and the use of expensive and toxic reagents. This paper describes a rapid scale-up synthesis accomplished in eight steps, which involves the coupling of phenol 17 with oxathiazolidine 18 as the key transformation.

中文翻译：

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(S)-N-(8-((2-Amino-2,4-dimethylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-yl)acetamide 的快速放大合成的开发, 一种有效的 Adaptor 相关激酶 1 抑制剂

( S )- N -(8-((2-Amino-2,4-dimethylpentyl)oxy)-5 H -chromeno[3,4- c ]pyridin-2-yl)acetamide ( 1 ) 是一种有效的接头-相关激酶 1 抑制剂，可能具有治疗神经性疼痛和其他神经系统疾病的潜力，包括精神分裂症、帕金森病、双相情感障碍和阿尔茨海默病。对于临床前研究，需要大量高质量的材料。制备这种化合物的最初发现路线存在放大问题，包括产率非常低的 C-O 偶联步骤以及使用昂贵且有毒的试剂。本文描述了一种通过八个步骤完成的快速放大合成，其中涉及苯酚的偶联17以恶噻唑烷18为关键转化。