2-[(3S)-2,6-dioxopiperidinyl]-4-nitro-1H-isoindole-1,3(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】34429

【品名】2-[(3S)-2,6-dioxopiperidinyl]-4-nitro-1H-isoindole-1,3(2H)-dione

【CA登记号】

【分子式】C₁₃H₉N₃O₆

【分子量】303.23108

【元素组成】C 51.49% H 2.99% N 13.86% O 31.66%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

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.

参考文献中间体

合成目标

【1】 Muller, G.W.; Huang, S.-Y.; Chen, R.; et al.; Amino-substituted thalidomide analogs: Potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999, 9, 11, 1625.
【2】 Stirling, D.I.; Chen, R.S.-C.; Muller, G.W. (Celgene Corp.); Substd. 2-(2,6-dioxopiperidin-3-yl)-phthalimides and 1-oxoisoindolines and method of reducing TNFalpha levels. EP 0925294; EP 0984955; US 5635517; WO 9803502; WO 9854170 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	34424	4-nitro-1H-isoindole-1,3(2H)-dione；3-nitrophthalimide	603-62-3	C₈H₄N₂O₄	详情	详情
(II)	34425	ethyl 4-nitro-1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate		C₁₁H₈N₂O₆	详情	详情
(III)	34426	tert-butyl (2S)-2,5-diamino-5-oxopentanoate		C₉H₁₈N₂O₃	详情	详情
(IV)	34427	tert-butyl (2S)-5-amino-2-(4-nitro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-oxopentanoate		C₁₇H₁₉N₃O₇	详情	详情
(V)	34428	(2S)-5-amino-2-(4-nitro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-oxopentanoic acid		C₁₃H₁₁N₃O₇	详情	详情
(VI)	34429	2-[(3S)-2,6-dioxopiperidinyl]-4-nitro-1H-isoindole-1,3(2H)-dione		C₁₃H₉N₃O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The cyclization of N-(benzyloxycarbonyl)-L-glutamine (I) by means of CDI in THF gives the piperidinedione (II), which is deprotected by means of HBr in AcOH to yield 3(S)-aminopiperidine-2,6-dione (III).The condensation of (III) with 3-nitrophthalic anhydride (IV) in hot DMF/AcOH affords 3(S)-phthalimido-piperidine-2,6-dione (V), which is finally reduced with H2 over Pd/C in dioxane/methanol to provide the target thalidomide derivative.

参考文献中间体

合成目标

【1】 D'Amato, R.J.; Shah, J.H.; Hunsucker, K.A.; Pribluda, V.; Treston, A.; Rougas, J.; Conner, B.P.; Swartz, G.M. (Children's Medical Center Corp.); Synthesis of 3-amino-thalidomide and its enantiomers. WO 0264083 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	26289	(2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid		C₁₃H₁₆N₂O₅	详情	详情
(II)	64520	benzyl (3S)-2,6-dioxopiperidinylcarbamate		C₁₃H₁₄N₂O₄	详情	详情
(III)	48171	(3S)-3-amino-2,6-piperidinedione		C₅H₈N₂O₂	详情	详情
(IV)	46407	4-nitro-2-benzofuran-1,3-dione；3-nitrophthalic anhydride	641-70-3	C₈H₃NO₅	详情	详情
(V)	34429	2-[(3S)-2,6-dioxopiperidinyl]-4-nitro-1H-isoindole-1,3(2H)-dione		C₁₃H₉N₃O₆	详情	详情

Extended Information