Ricasetron, BRL-46470

利卡司琼Chemical Name: endo-3,3-Dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydroindole-1-carboxamide
CAS No. 117086-68-7
项目整合开发状态: Phase II
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The reaction of 7-ethyl-10-hydroxycamptothecin (I) with phosgene gives 7-ethyl-10-(chlorocarbonyloxy)camptothecin (II),which is then condensed with 4-(1-piperidyl)piperidine.

合成路线:The target compound has been obtained by condensation of 3.3-dimethylindoline-1-carbonyl chloride (IV) with endo-8-methyl-8-azabicyclo[3.2.1]octan-3-amine (II) by means of triethylamine followed by salification with HCl.The intermediates (II) and (IV) have been obtained as follows:A) The metthylation of 3-methylindole (III) with methylmagnesium iodid / methyl iodid,followed by hydrogenation with H2/Pt in acetic acid gives 3,3-dimethylindoline (I),which is then treated with phosghene / Et3N to afford intermediate (IV).B) The reductocondensation of 8-methyl-para-bicyclo[3.2.1]octan-3-one (V) with benzylamine and H2/Pt gives the secondary benzylamine (VI),which is finally deprotected by hydrogenation over Pd/C to give intermediate (II).
📌 参考资料/链接:
参考文献标题:New camptothecin derivs.and process for preparing same
文献作者:Miyasaka,T.; Mutai,M.; Nokata,K.; Sawada,S.; Sugino,E.(Yakult Honsha Co.,Ltd.)
参考来源:EP 0137145; JP 1985019790

📄 详细内容


合成路线:The target compound has been obtained by condensation of 3.3-dimethylindoline-1-carbonyl chloride (IV) with endo-8-methyl-8-azabicyclo[3.2.1]octan-3-amine (II) by means of triethylamine followed by salification with HCl.The intermediates (II) and (IV) have been obtained as follows:A) The metthylation of 3-methylindole (III) with methylmagnesium iodid / methyl iodid,followed by hydrogenation with H2/Pt in acetic acid gives 3,3-dimethylindoline (I),which is then treated with phosghene / Et3N to afford intermediate (IV).B) The reductocondensation of 8-methyl-para-bicyclo[3.2.1]octan-3-one (V) with benzylamine and H2/Pt gives the secondary benzylamine (VI),which is finally deprotected by hydrogenation over Pd/C to give intermediate (II).

参考文献标题:Certain 2,3-dihydro-indole-1-carboxamido-N-[8-azabicyclo(3.2.1)octan-3-yl] derivatives having 5-HT-antagonist activity
文献作者:Joiner,K.A.; King,F.D.(SmithKline Beecham plc)
参考来源:EP 0363466; JP 1990503569; US 4871744; US 5049556; WO 8909217


合成路线:The target compound has been obtained by condensation of 3.3-dimethylindoline-1-carbonyl chloride (IV) with endo-8-methyl-8-azabicyclo[3.2.1]octan-3-amine (II) by means of triethylamine followed by salification with HCl.The intermediates (II) and (IV) have been obtained as follows:A) The metthylation of 3-methylindole (III) with methylmagnesium iodid / methyl iodid,followed by hydrogenation with H2/Pt in acetic acid gives 3,3-dimethylindoline (I),which is then treated with phosghene / Et3N to afford intermediate (IV).B) The reductocondensation of 8-methyl-para-bicyclo[3.2.1]octan-3-one (V) with benzylamine and H2/Pt gives the secondary benzylamine (VI),which is finally deprotected by hydrogenation over Pd/C to give intermediate (II).

参考文献标题:BRL46470A
文献作者:Blackburn,T.; King,F.
参考来源:Drugs Fut 1992,17(11),987


合成路线:The target compound has been obtained by condensation of 3.3-dimethylindoline-1-carbonyl chloride (IV) with endo-8-methyl-8-azabicyclo[3.2.1]octan-3-amine (II) by means of triethylamine followed by salification with HCl.The intermediates (II) and (IV) have been obtained as follows:A) The metthylation of 3-methylindole (III) with methylmagnesium iodid / methyl iodid,followed by hydrogenation with H2/Pt in acetic acid gives 3,3-dimethylindoline (I),which is then treated with phosghene / Et3N to afford intermediate (IV).B) The reductocondensation of 8-methyl-para-bicyclo[3.2.1]octan-3-one (V) with benzylamine and H2/Pt gives the secondary benzylamine (VI),which is finally deprotected by hydrogenation over Pd/C to give intermediate (II).
参考文献标题:3alpha-(2-Diethylaminoethyl)-aminotropane and related compounds
文献作者:Archer,S.; Lewis,T.R.; Unser,M.J.
参考来源:J Am Chem Soc 1957,794194-8


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