Development of a Rapid Scale-Up Synthesis of (S)‑N‑(8-((2-Amino-2,4-dimethylpentyl)oxy)‑5H‑chromeno[3,4‑c]pyridin-2-yl)acetamide, a Potent Adaptor-Associated Kinase 1 Inhibitor

(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.