ER-127528
Chemical Name: (+)-2-Fluoro-2-[1-(3-fluorobenzyl)piperidin-4-ylmethyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one hydrochloride
CAS No. 290308-82-6 (undefined isomer), 290308-83-7 (undefined isomer, free base)
项目整合开发状态: Preclinical
项目研究机构: Eisai (Originator)
合成路线:The lithium enolate of the indanone derivative (I) is fluorinated by treatment with N-fluorobenzenesulfonimide,to afford the corresponding fluoro ketone,which is finally isolated as the corresponding hydrochloride salt.
📌 参考资料/链接：
参考文献标题:Fluorides of 4-substd.piperidine derivs.
文献作者:Sugimoto,H.; Yamanishi,Y.; Shibata,T.; Kosaka,T.; Suzuki,E.; Takeuchi,Y.; Imura,Y.(Eisai Co.,Ltd.)
参考来源:EP 1157989; JP 2000319258; WO 0051985
📄 详细内容
合成路线:The title compound is also prepared by a related method.Indanone (I) is fluorinated by means of N-fluorobenzenesulfonimide in the presence of lithium hexamethyldisilazide,to afford the corresponding fluoro ketone (II).Subsequent dealkylation of the N-benzyl group of (II) is accomplished by treatment with 1-chloroethyl chloroformate,to produce the intermediate carbamate (III),which is then decarboxylated to the secondary amine (IV) in boiling MeOH.Finally,piperidine (IV) is reductively alkylated with 3-fluorobenzaldehyde (V) in the presence of NaBH(OAc)3.
参考文献标题:Recent advances in the study of acetylcholinesterase inhibitor "donepezil" (1): Synthesis and structure-activity relationships of fluorine-introduced donepezil and related compounds
文献作者:Takeuchi,Y.; Yamanishi,Y.; Sugimoto,H.; Suzuki,N.; Iimura,Y.; Kawakami,Y.; Inoue,A.; Kuriya,Y.; Kosasa,T.
参考来源:221st ACS Natl Meet (April 1 2001,San Diego) 2001,Abst MEDI 67