文献类型：期刊文献

英文题名：A Novel, Practical, and Efficient Synthetic Process for Chiral 10-Aza-isoergoline Scaffold of the Antipsychotic Candidate IHCH7041

作者：Li, Ruipeng[2];Bian, Wentao[1];Xie, Jianshu[2];Xia, Guangxin[2];Zhao, Jianhong[1]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China;[2]Shanghai Pharmaceut Holding Co Ltd, Cent Res Inst, State Key Lab Innovat Immunotherapy, Shanghai 201203, Peoples R China

年份：2026

卷号：30

期号：6

起止页码：1662

外文期刊名：ORGANIC PROCESS RESEARCH & DEVELOPMENT

收录：;EI(收录号：20262520957995);WOS:【SCI-EXPANDED(收录号:WOS:001775824800001)】；

基金：This study was supported by Shanghai Science and Technology Program Project (23S11902300).

语种：英文

外文关键词：10-aza-isoergoline; antipsychotic candidate; process development; chiral resolution

摘要：A novel, practical, and scalable synthetic route has been developed for (S)-N1, the pivotal chiral 10-aza-isoergoline scaffold of the antipsychotic candidate IHCH7041. This process features a concise, chromatography-free synthesis of racemic N1 from commercially available starting materials with a significantly increased yield of 24.9%, followed by its first successful optical resolution via diastereomeric salt formation with dibenzoyl-L-tartaric acid. Through systematic optimization of each step, the route was successfully executed on a multikilogram scale, delivering (S)-N1 in high yield with excellent chemical purity (>99%) and enantiomeric excess (>98.5%). Key advantages include operational simplicity, mild conditions, avoidance of specialized equipment or hazardous reagents, and significant cost reduction, making it highly suitable for large-scale production.