N(2)-[(benzyloxy)carbonyl]glutamine -Drug Synthesis Database

【结构式】

【分子编号】37578

【品名】N(2)-[(benzyloxy)carbonyl]glutamine

【CA登记号】

【分子式】C₁₃H₁₆N₂O₅

【分子量】280.28052

【元素组成】C 55.71% H 5.75% N 9.99% O 28.54%

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：(I)

The esterification of N2-(benzyloxycarbonyl)-D,L-glutamine (I) with methyl iodide and KHCO3 in DMF gives the corresponding methyl ester (II), which is cyclized to benzyl D,L-2,6-dioxo-3-piperidinecarbamate (III) by heating. The hydrogenolysis of (III) with H2 over Pd/C in methanol yields D,L-2-aminoglutarimide (IV), which is condensed with 2-chloroethyl isocyanate (V) in DMF affording 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)urea (VI). Finally, this compound is nitrosated in the usual way with NaNO2 in formic acid.

参考文献中间体

合成目标

【1】 Johnston, T.P.; et al.; The synthesis of potential anticancer agents. XXXVI. N-Nitrosoureas. II. Haloalkyl derivatives. J Med Chem 1966, 9, 6, 892-911.
【2】 Woodman, R.J.; Castaner, J.; PCNU. Drugs Fut 1981, 6, 8, 481.

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)	37578	N(2)-[(benzyloxy)carbonyl]glutamine		C₁₃H₁₆N₂O₅	详情	详情
(II)	37579	methyl 5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoate		C₁₄H₁₈N₂O₅	详情	详情
(III)	37575	benzyl 2,6-dioxo-3-piperidinylcarbamate		C₁₃H₁₄N₂O₄	详情	详情
(IV)	37576	3-amino-2,6-piperidinedione；3-aminopiperidine-2,6-dione；2-amino-Glutarimide；Glutamimide;a-Aminoglutarimide	2353-44-8	C₅H₈N₂O₂	详情	详情
(V)	11237	1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate	1943-83-5	C₃H₄ClNO	详情	详情
(VI)	37577	N-(2-chloroethyl)-N'-(2,6-dioxo-3-piperidinyl)urea		C₈H₁₂ClN₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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).

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Bayes, M.; CC-5013. Drugs Fut 2003, 28, 5, 425.
【2】 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.
【3】 Stirling, D.I.; Muller, G.W.; Chen, R.S.-C. (Celgene Corp.); Substd. 2-(2,6-dioxopiperidin-3-yl)-phthalimides and -1-oxoisoindolines and method of reducing TNFalpha levels. EP 0925294; US 5635517; WO 9803502 .

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)	37578	N(2)-[(benzyloxy)carbonyl]glutamine		C₁₃H₁₆N₂O₅	详情	详情
(II)	37575	benzyl 2,6-dioxo-3-piperidinylcarbamate		C₁₃H₁₄N₂O₄	详情	详情
(III)	37576	3-amino-2,6-piperidinedione；3-aminopiperidine-2,6-dione；2-amino-Glutarimide；Glutamimide;a-Aminoglutarimide	2353-44-8	C₅H₈N₂O₂	详情	详情
(IV)	62310	Methyl 3-nitro-o-toluate; 2-Methyl-3-nitrobenzoic acid	59382-59-1	C₉H₉NO₄	详情	详情
(V)	62309	methyl 2-(bromomethyl)-3-nitrobenzoate	98475-07-1	C₉H₈BrNO₄	详情	详情
(VI)	62311	3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-piperidinedione		C₁₃H₁₁N₃O₅	详情	详情

Extended Information