LB-50016

Chemical Name: 2-[4-(3-Phenylpyrrolidin-1-yl)butyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide
CAS No. 228579-02-0
项目整合开发状态: Preclinical
项目研究机构: LG Chem (Originator)
合成路线:The sulfonylation of 1-benzylpyrrolidin-3-ol by means of mesyl or tosyl chlorides gives the corresponding sulfonates (II) or (III),which are condensed with the diphenyl cuprate lithium yielding 1-benzyl-3-phenylpyrrolidine (IV).The debenzylation of (IV) with ammonium formate over Pd/C in methanol affords 3-phenylpyrrolidine (V),which is finally condensed with 2-(4-bromobutyl)-1,2-benzoisothiazol-3-one S,S-dioxide (VI) by means of triethylamine in acetonitrile.

合成路线:The sulfonylation of 1-benzylpyrrolidin-3-ol by means of mesyl or tosyl chlorides gives the corresponding sulfonates (II) or (III),which are condensed with the bis(4-fluorophenyl)cuprate lithium (IV) yielding 1-benzyl-3-(4-fluorophenyl) pyrrolidine (V).The debenzylation of (V) with ammonium formate over Pd/C in methanol affords 3-(4-fluorophenyl)pyrrolidine (VI),which is finally condensed with 2-(4-bromobutyl)-1,2-benzoisothiazol-3-one S,S-dioxide (VII) by means of triethylamine in acetonitrile.

合成路线:Treatment of 1-benzyl-3-hydroxypyrrolidine (I) with methanesulfonyl chloride in the presence of DMAP and Et3N affords mesylate (II).Subsequent displacement of the mesylate group of (II) with the diarylcuprate reagent generated from 4-fluorophenyllithium (III) and cuprous bromide gives the 3-aryl pyrrolidine (IV).The N-benzyl group of (IV) is then removed by transfer hydrogenolysis with ammonium formate and Pd/C,yielding the secondary amine (V).This is finally alkylated with 2-(4-bromobutyl)-3-oxo-1,2-benzisothiazole 1,1-dioxide (VI) in the presence of Et3N in refluxing acetonitrile.