RS-1653

Chemical Name: 2-(4-Fluoro-7-methyl-1,2-benzisoxazol-3-yloxy)ethanamine hydrochloride
CAS No. 178746-70-8, 178746-69-5 (free base)
项目整合开发状态: Preclinical
项目研究机构: Sankyo (Originator)
合成路线:Methyl 2,6-difluorobenzoate (I) was converted to the hydroxamic acid (II) upon treatment with hydroxylamine and KOH.Cyclization of the fluorobenzohydroxamic acid (II) using KOH in boiling butanol produced the 3-hydroxybenzisoxazole (III),which was subjected to Mitsunobu coupling with N-Boc-ethanolamine (IV) to furnish the N-Boc-aminoethyl ether (V).Metalation of (V) with butyllithium at -70 C,followed by quenching with iodomethane gave rise to two regioisomeric methylbenzisoxazoles (VI) and (VII),which were separated by column chromatography.The target 7-methyl benzisoxazole (VII) was then deprotected under acidic conditions to yield the title aminoethoxy derivative.