Laniquidar, R-101933
甲基11-[1-[2-[4-(喹啉-2-甲氧基)苯基]乙基,哌啶-4-酰胺]-5,6-二氢亚咪唑[2,1-b][3]苯甲西泮-3-羧酸盐Chemical Name: 11-[1-[2-[4-(2-Quinolylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-carboxylic acid methyl ester
CAS No. 197509-46-9, 278798-78-0 (error in cn), 221619-66-5 (fumarate)
项目整合开发状态: Phase I
项目研究机构: Janssen (Originator)
合成路线:Condensation of 4-hydroxyphenylethanol (I) with 2-(chloromethyl)quinoline (II) in ethanolic KOH provided ether (III).The free hydroxyl group of (III) was then converted to the corresponding mesylate (IV) by treatment with methanesulfonyl chloride and Et3N.Alkylation of 11-(4-piperidinylidene)-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-methanol (V) with mesylate (IV) in the presence of NaHCO3 gave adduct (VI).The primary alcohol of (VI) was oxidized to aldehyde (VII) using MnO2 in CH2Cl2.Finally,aldehyde (VII) was further oxidized to the title methyl ester by means of MnO2 in the presence of sodium cyanate in HOAc-MeOH.
📌 参考资料/链接：
参考文献标题:Fused imidazole derivs.as multidrug resistance modulators
文献作者:Janssens,F.E.; Leenaerts,J.E.; Sommen,F.M.; Surleraux,D.L.N.G.(Janssen Pharmaceutica NV)
参考来源:EP 0888352; JP 2000505477; US 6218381; WO 9734897
📄 详细内容
合成路线:Condensation of 4-hydroxyphenylethanol (I) with 2-(chloromethyl)quinoline (II) in ethanolic KOH provided ether (III).The free hydroxyl group of (III) was then converted to the corresponding mesylate (IV) by treatment with methanesulfonyl chloride and Et3N.Alkylation of 11-(4-piperidinylidene)-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-methanol (V) with mesylate (IV) in the presence of NaHCO3 gave adduct (VI).The primary alcohol of (VI) was oxidized to aldehyde (VII) using MnO2 in CH2Cl2.Finally,aldehyde (VII) was further oxidized to the title methyl ester by means of MnO2 in the presence of sodium cyanate in HOAc-MeOH.
参考文献标题:Fused imidazole derivs.for improving oral bioavailability of pharmaceutical agents
文献作者:Snoeck,H.J.M.(Janssen Pharmaceutica NV)
参考来源:WO 9913871
产品链接: CAS No. 197509-46-9›› 产品链接: CAS No.278798-78-0››