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【结 构 式】

【分子编号】69002

【品名】5-tert-butylimidazole-4-carbaldehyde;5-(1,1-dimethylethyl)-1H-Imidazole-4-carboxaldehyde;4-(1,1-dimethylethyl)-1H-Imidazole-5-carboxaldehyde

【CA登记号】714273-83-3

【 分 子 式 】C8H12N2O

【 分 子 量 】152.19616

【元素组成】C 63.13% H 7.95% N 18.41% O 10.51%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(III)

2,5-Piperazinedione (I) is acylated with acetic anhydride at 110 oC in the presence of catalytic NaOAc to afford the diacetyl derivative (II). Claisen condensation of N,N’-diacetyl-2,5-piperazinedione (II) with 5-tert-butylimidazole-4-carbaldehyde (III) by means of Cs2CO3 in DMF at room temperature leads to the monoacetylated (imidazolylmethylene) piperazinedione (IV), which is finally condensed with benzaldehyde (V) in the presence of Cs2CO3 in DMF at 80 °C. In a related alternative method, diketopiperazine (II) is first condensed with benzaldehyde (V) in the presence of Cs2CO3 in DMF at room temperature, yielding the benzylidene piperazinedione (VI), which is subsequently condensed with the imidazole-aldehyde (III) by means of Cs2CO3 in hot DMF .

1 Hayashi, Y., Grodberg, J., Palladino, M. (Nereus Pharmaceuticals, Inc). Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins dehydrophenylahistins and analogs thereof. EP 1529044, JP 2006511534, WO 2004054498.
2 Palladino, M.A., Lloyd, G.K., Hayashi, Y., Nicholson, B. (Nereus Pharmaceuticals, Inc). Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof. EP 1711487, JP 2007520565, WO 2005077940.
3 Palladino, M., Lloyd, G.K., Hayashi, Y. (Nereus Pharmaceuticals, Inc). Analogs of dehydrophenylahistins and their therapeutic use. EP 1926724, US 2007078138, WO 2007035841.
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) 29800 2,5-piperazinedione;2,5-diketopiperazine;cycloglycylglycine;2,5-dioxopiperazine;cyclodiglycine;cyclo(glycylglycyl) 106-57-0 C4H6N2O2 详情 详情
(II) 19188 1,4-diacetyl-2,5-piperazinedione;N,N'-DIACETYLGLYCINE ANHYDRIDE;1,4-DIACETYL-PIPERAZINE-2,5-DIONE;1,4-DIACETYLTETRAHYDRO-2,5-PYRAZINEDIONE;1,4-DIACETYL-2,5-DIKETOPIPERAZINE;1,4-DIACETYL-2,5-DIOXOPIPERAZINE 3027-05-2 C8H10N2O4 详情 详情
(III) 69002 5-tert-butylimidazole-4-carbaldehyde;5-(1,1-dimethylethyl)-1H-Imidazole-4-carboxaldehyde;4-(1,1-dimethylethyl)-1H-Imidazole-5-carboxaldehyde 714273-83-3 C8H12N2O 详情 详情
(IV) 69003 (Z)-1-acetyl-3-((5-(tert-butyl)-1H-imidazol-4-yl)methylene)piperazine-2,5-dione   C14H18N4O3 详情 详情
(V) 10498 Benzaldehyde;Benzoic aldehyde;Phenylmethanal 100-52-7 C7H6O 详情 详情
(VI) 19189 1-acetyl-3-[(Z)-benzylidene]-2,5-piperazinedione C13H12N2O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

The intermediate 5-tert-butylimidazole-4-carbaldehyde (III) is prepared by reaction of ethyl pivaloyl acetate (VII) with sulfuryl chloride in chloroform to provide the 2-chloro derivative (VIII), which is cyclized with formamide (IX) in the presence of a trace of water in a sealed tube at 150 oC, affording ethyl 5-tert-butylimidazole-4-carboxylate (X). Reduction of ester (X) with LiAlH4 in THF gives alcohol (XI), which is finally oxidized to the target carbaldehyde (III) using MnO2 in acetone .

1 Hayashi, Y., Grodberg, J., Palladino, M. (Nereus Pharmaceuticals, Inc). Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins dehydrophenylahistins and analogs thereof. EP 1529044, JP 2006511534, WO 2004054498.
2 Palladino, M.A., Lloyd, G.K., Hayashi, Y., Nicholson, B. (Nereus Pharmaceuticals, Inc). Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof. EP 1711487, JP 2007520565, WO 2005077940.
3 Palladino, M., Lloyd, G.K., Hayashi, Y. (Nereus Pharmaceuticals, Inc). Analogs of dehydrophenylahistins and their therapeutic use. EP 1926724, US 2007078138, WO 2007035841.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(III) 69002 5-tert-butylimidazole-4-carbaldehyde;5-(1,1-dimethylethyl)-1H-Imidazole-4-carboxaldehyde;4-(1,1-dimethylethyl)-1H-Imidazole-5-carboxaldehyde 714273-83-3 C8H12N2O 详情 详情
(VII) 69004 ethyl 4,4-dimethyl-3-oxopentanoate;Ethyl pivaloylacetate 17094-34-7 C9H16O3 详情 详情
(VIII) 69005 ethyl 2-chloro-4,4-dimethyl-3-oxopentanoate   C9H15ClO3 详情 详情
(IX) 16598 Formamide 75-12-7 CH3NO 详情 详情
(X) 69006 ethyl 5-(tert-butyl)-1H-imidazole-4-carboxylate   C10H16N2O2 详情 详情
(XI) 69007 (5-(tert-butyl)-1H-imidazol-4-yl)methanol   C8H14N2O 详情 详情
Extended Information