产量(工程)
反激动剂
吡嗪
兴奋剂
亲核芳香族取代
化学
立体化学
受体
组合化学
药物化学
亲核取代
生物化学
材料科学
冶金
作者
Changwei Mu,Xiaolong Li,Yang YongTan,Yusheng Zhou,Chunhua Wang,Kevin Doyle,Naidong Ye,Anil Mistry,Roland W. Bürli
标识
DOI:10.1021/acs.oprd.2c00181
摘要
CVN424 is a drug candidate, which is being investigated in clinical trials for the treatment of motor fluctuations associated with Parkinson's disease. We herein describe the process development of an efficient synthetic route that delivered several kilograms of the drug substance. The synthesis included diacylation of commercially available 3,4-diaminopyridine 1 with diethyl oxalate to give 2 and chlorination with POCl3 to give pyrido[3,4-b]pyrazine 3, followed by two sequential nucleophilic aromatic substitutions. A final hydrogenation and acetylation of intermediate 7 provided CVN424. Overall, a safe and robust synthesis was developed, which occurred in five linear steps with an overall yield of 15%.
科研通智能强力驱动
Strongly Powered by AbleSci AI