合成路线:Treatment of 3-nitrophthalimide (I) with ethyl chloroformate and triethylamine produced 3-nitro-N-(ethoxycarbonyl)phthalimide (II),which was condensed with L-glutamine tert-butyl ester hydrochloride (III) to afford the phthaloyl glutamine derivative (IV).Acidic cleavage of the tert-butyl ester of (IV) provided the corresponding carboxylic acid (V).This was cyclized to the required glutarimide (VI) upon treatment with thionyl chloride and then with triethylamine.The nitro group of (VI) was finally reduced to amine by hydrogenation over Pd/C.
合成路线:Cyclization of N-(benzyloxycarbonyl)glutamine (I) by means of CDI in refluxing THF gives 3-(benzyloxycarbonylamino)piperidine-2,6-dione (II),which is deprotected with H2 over Pd/C in ethyl acetate/4N HCl to yield 3-aminopiperidine-2,6-dione hydrochloride (III).Bromination of 2-methyl-3-nitrobenzoic acid methyl ester (IV) with NBS in CCl4 provides 2-(bromomethyl)-3-nitrobenzoic acid methyl ester (V),which is cyclized with the aminopiperidine (III) by means of triethylamine in hot DMF to afford 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (VI).Finally,the nitro group of compound (VI) is reduced with H2 over Pd/C in methanol (1,2).
参考文献标题:Amino-substituted thalidomide analogs: Potent inhibitors of TNF-alpha production
文献作者:Muller,G.W.; Chen,R.; Huang,S.Y.; Corral,L.G.; Wong,L.M.; Patterson,R.T.; Chen,Y.; Kaplan,G.; Stirling,D.I.
参考来源:Bioorg Med Chem Lett 1999,9(11),1625
合成路线:Cyclization of N-(benzyloxycarbonyl)glutamine (I) by means of CDI in refluxing THF gives 3-(benzyloxycarbonylamino)piperidine-2,6-dione (II),which is deprotected with H2 over Pd/C in ethyl acetate/4N HCl to yield 3-aminopiperidine-2,6-dione hydrochloride (III).Bromination of 2-methyl-3-nitrobenzoic acid methyl ester (IV) with NBS in CCl4 provides 2-(bromomethyl)-3-nitrobenzoic acid methyl ester (V),which is cyclized with the aminopiperidine (III) by means of triethylamine in hot DMF to afford 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (VI).Finally,the nitro group of compound (VI) is reduced with H2 over Pd/C in methanol (1,2).
参考文献标题:CC-5013
文献作者:Sorbera,L.A.; Castar,J.; Bay閟,M.
参考来源:Drugs Fut 2003,28(5),425
产品链接: CAS No. 191732-72-6›› 产品链接: CAS No.443912-14-9››