methyl 2-(bromomethyl)-3-nitrobenzoate -Drug Synthesis Database

【结构式】

【分子编号】62309

【品名】methyl 2-(bromomethyl)-3-nitrobenzoate

【CA登记号】98475-07-1

【分子式】C₉H₈BrNO₄

【分子量】274.07086

【元素组成】C 39.44% H 2.94% Br 29.15% N 5.11% O 23.35%

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：(V)

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

合成路线2

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Muller GW, Chen R, Saindane MT, et aL 2006. Processes for the preparation of substituted 2-(2,6-dioxopiperidirr3-yl)-l-oxoisoindolines,e.g.,Revlimid, using p-toluenesulfonic acid or base-mediated cyclization as the key step. US 2006052609

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)	66478	(S)-5-amino-2-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acid		C₁₃H₁₆N₂O₅	详情	详情
(II)	66479	(S)-2,5-diamino-5-oxopentanoic acid		C₅H₁₀N₂O₃	详情	详情
(III)	62309	methyl 2-(bromomethyl)-3-nitrobenzoate	98475-07-1	C₉H₈BrNO₄	详情	详情
(IV)	66480	(R)-methyl 5-amino-2-(4-nitro-1-oxoisoindolin-2-yl)-5-oxopentanoate		C₁₄H₁₅N₃O₆	详情	详情
(V)	66481	(R)-methyl 5-amino-2-(4-amino-1-oxoisoindolin-2-yl)-5-oxopentanoate		C₁₄H₁₇N₃O₄	详情	详情

Extended Information