VER-5593
Chemical Name: 1-[5-Fluoro-6-methylsulfanyl-2,3-dihydro-1H-indol-1-yl]propan-2(S)-amine
CAS No. 259858-34-9, 259858-35-0 (fumarate salt), 259859-03-5 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Vernalis (Originator)
合成路线:Reaction of 5,6-difluoroisatin (I) with sodium methanethiolate affords thioether (II).Subsequent reduction of isatin (II) with LiAlH4 provides 5-fluoro-6-methylsulfanylindole (III).Alkylation of indole (III) with (S)-2-(t-butoxycarbonylamino)propyl methanesulfonate (IV) in the presence of KOH in DMSO leads to the N-alkylated indole (V),which is further reduced to the corresponding indoline (VI) by means of NaBH3CN in AcOH.The N-Boc protecting group of (VI) is finally removed by treatment with trifluoroacetic acid in CH2Cl2 (1,2).
📌 参考资料/链接：
参考文献标题:Indoline derivs.as 5-HT2B and/or 5-HT2C receptor ligands
文献作者:Bebbington,D.; Gaur,S.; Adams,D.R.; Monck,N.J.; Bentley,J.M.; Hamlyn,R.J.; Duncton,M.A.J.; Dawson,C.E.; Pratt,R.M.; George,A.R.; Roffey,J.R.A.(Vernalis Research Ltd.)
参考来源:EP 1109784; JP 2002523491; US 6380238; WO 0012475
📄 详细内容
合成路线:Reaction of 5,6-difluoroisatin (I) with sodium methanethiolate affords thioether (II).Subsequent reduction of isatin (II) with LiAlH4 provides 5-fluoro-6-methylsulfanylindole (III).Alkylation of indole (III) with (S)-2-(t-butoxycarbonylamino)propyl methanesulfonate (IV) in the presence of KOH in DMSO leads to the N-alkylated indole (V),which is further reduced to the corresponding indoline (VI) by means of NaBH3CN in AcOH.The N-Boc protecting group of (VI) is finally removed by treatment with trifluoroacetic acid in CH2Cl2 (1,2).
参考文献标题:Indolines as human 5-HT2C receptor ligands
文献作者:Adams,D.R.; Bebbington,D.; Bentley,J.M.; Benwell,K.; Bickerdike,M.J.; Cliffe,I.A.; Davidson,J.E.; Dawson,C.E.; Duncton,M.A..J.; Gaur,S.; George,A.R.; Giles,P.R.; Hamlyn,R.J.; Kennett,G.A.; Knight,A.R.; Malcolm,C.; Mansell,H.L.; et al.
参考来源:28th Natl Med Chem Symp (June 8 2002,San Diego) 2002,Abst 12