SB-224289
(2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)-[1,1'-二苯基]-4-基)(1'-甲基-6,7-二氢螺[呋喃并[2,3-f]吲哚-3,4'-哌啶]-5(2H)-基)甲酮 1'-甲基-5-[[[2'-甲基-4'-(5-甲基-1,2,4-4-恶二唑-3-基)联苯-4-基]羰基]-2,3,6,7-四氢螺[呋喃[2,3-f]吲哚-3,4'-哌啶盐酸盐 Chemical Name: 1'-Methyl-5-[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-ylcarbonyl]-2,3,6,7-tetrahydro-5H-spiro[furo[2,3-f]indole-3,4'-piperidine]
CAS No. 180083-23-2, 180084-26-8 (monoHCl), 180084-29-1 (monooxalate salt)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Friedel-Crafts acylation of 1-acetylindoline (I) with acetyl chloride and AlCl3 afforded ketone (II).Subsequent Baeyer-Villiger rearrangement using peracetic acid yielded acetate ester (III),which was hydrolyzed with NaOH to give phenol (IV).Bromination of (IV) with NBS in AcOH then provided bromo hydroxy indoline (V).Alkylation with 1-methyl-tetrahydropyridine-4-methanol (VI) under Mitsunobu conditions produced ether (VII).This was cyclized to the spirocyclic compound (VIII) using AIBN and tributyltin hydride in refluxing benzene.Then,amide hydrolysis in hydroalcoholic HCl gave (IX),which was finally condensed with acid chloride (X) to provide the desired amide.
📌 参考资料/链接：
参考文献标题:The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function b
文献作者:Gaster,L.M.; Blaney,F.E.; Davies,S.; Duckworth,D.M.; Ham,P.; Jenkins,S.; Jennings,A.J.; Joiner,G.F.; King,F.D.; Mulholland,K.R.; Wyman,P.A.; Hagan,J.J.; Hatcher,J.; Jones,B.J.; Middlemiss,D.N.; Price,G.W.; Riley,G.; Roberts,C.; et al.
参考来源:J Med Chem 1998,41(8),1218
📄 详细内容
合成路线:Friedel-Crafts acylation of 1-acetylindoline (I) with acetyl chloride and AlCl3 afforded ketone (II).Subsequent Baeyer-Villiger rearrangement using peracetic acid yielded acetate ester (III),which was hydrolyzed with NaOH to give phenol (IV).Bromination of (IV) with NBS in AcOH then provided bromo hydroxy indoline (V).Alkylation with 1-methyl-tetrahydropyridine-4-methanol (VI) under Mitsunobu conditions produced ether (VII).This was cyclized to the spirocyclic compound (VIII) using AIBN and tributyltin hydride in refluxing benzene.Then,amide hydrolysis in hydroalcoholic HCl gave (IX),which was finally condensed with acid chloride (X) to provide the desired amide.
参考文献标题:SB-224289 - a highly selective 5-HT1B receptor inverse agonist
文献作者:Gaster,L.; et al.
参考来源:15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998,Edinburgh) 1998,Abst P.259
产品链接: CAS No. 180083-23-2›› 产品链接: CAS No.180084-26-8››