Lenalidomide, IMID-5013, IMiD3, CDC-5013, CDC-501, CC-5013, ENMD-0997, Revimid, Revlimid, -Drug Synthesis Database

【结构式】

【药物名称】Lenalidomide, IMID-5013, IMiD3, CDC-5013, CDC-501, CC-5013, ENMD-0997, Revimid, Revlimid

【化学名称】3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione

【CA登记号】191732-72-6, 443912-14-9 (deleted CAS)

【分子式】C₁₃H₁₃N₃O₃

【分子量】259.26686

【开发单位】Celgene (Orphan Drug), Children's Medical Center Corp. (Not Determined), EntreMed (Not Determined), Celgene (Licensee)

【药理作用】Brain Cancer Therapy, GASTROINTESTINAL DRUGS, Glioblastoma MultiformeTherapy, Inflammatory Bowel Disease, Agents for, Melanoma Therapy, Multiple Myeloma Therapy, Myelodysplastic Syndrome Therapy, Oncolytic Drugs, Solid Tumors Therapy, Angiogenesis Inhibitors, Antiinflammatory Drugs, TNF-alpha Production Inhibitors

合成路线1 合成路线2

合成路线1

参考文献中间体

【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

合成路线2

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

【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