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【结 构 式】 
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【分子编号】16143 【品名】3-(4-iodobutyl)-1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione 【CA登记号】 |
【 分 子 式 】C14H16IN3O2 【 分 子 量 】385.20453 【元素组成】C 43.65% H 4.19% I 32.94% N 10.91% O 8.31% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of 1-(benzylideneamino)imidazolidine-2,4-dione (I) with 1-bromo-4-chlorobutane (II) by means of NaH in DMF at 100 C yields 1-(benzylideneamino)-3-(4-chlorobutyl)imidazolidine-2,4-dione (III), which is treated with NaI in refluxing acetone affording the corresponding 4-iodobutyl derivative (IV). The thermal condensation of (IV) with 1-methylpiperazine (V) in refluxing DMF gives the expected condensation product (VI), which is debenzylated by hydrogenation with H2 over Pd/C in 2N HCl giving 1-amino-3-[4-(4-methylpiperazin-1-yl)butyl]imidazolidine-2,4-dione (VII). Finally, this compound is condensed with 5-(4-chlorophenyl)furan-2-carbaldehyde (VIII) in DMF at room temperature.
| 【1】 Robinson, C.P.; Robinson, K.A.; Castaner, J.; Azimilide Hydrochloride. Drugs Fut 1997, 22, 6, 601. |
| 【2】 Pelosi, S.S. Jr.; Yu, C.-NN.; Calcagno, M.A. (The Procter & Gamble Co.); Novel 4-oxocyclic ureas useful as antiarrhythmic and antifibrillatory agents. EP 0598061; JP 1994509804; US 5462940; WO 9304061 . |
| 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) | 16140 | 1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione | C10H9N3O2 | 详情 | 详情 | |
| (II) | 16141 | 1-bromo-4-chlorobutane | 6940-78-9 | C4H8BrCl | 详情 | 详情 |
| (III) | 16142 | 3-(4-chlorobutyl)-1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione | C14H16ClN3O2 | 详情 | 详情 | |
| (IV) | 16143 | 3-(4-iodobutyl)-1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione | C14H16IN3O2 | 详情 | 详情 | |
| (V) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (VI) | 16145 | 3-[4-(4-methylpiperazino)butyl]-1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione | C19H27N5O2 | 详情 | 详情 | |
| (VII) | 16146 | 1-amino-3-[4-(4-methylpiperazino)butyl]-1H-imidazole-2,4(3H,5H)-dione | C12H23N5O2 | 详情 | 详情 | |
| (VIII) | 16147 | 5-(4-Chloro-phenyl)-furan-2-carbaldehyde; 5-(4-Chlorophenyl)-2-furaldehyde | 34035-03-5 | C11H7ClO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)Addition of benzylmagnesium chloride to O-(trimethylsilyl)cyanohydrin (II) (obtained from phenylacetaldehyde (I) and Me3SiCN), led to benzylacyloin (III). Esterification with ethyl oxalyl chloride (IV) in the presence of Et3N afforded oxalate (V), which was cyclized with DBU in cold DMF to provide dihydrogrevillin (VI). This was methylated with ethereal diazomethane to give ether (VII), and then brominated in AcOH. Elimination of the resulting bromide (VIII) by treatment with DBU produced (IX), which was demethylated with BBr3 to afford grevillin (X). This compound was isomerized with NaOEt in EtOH to produce terphenyl quinone (XI). Finally, Perkin reaction with phenylacetic acid (XII), followed by treatment with HBr furnished the title compound.
| 【1】 Pattenden, G.; et al.; Synthesis of grevillins and their biogenetic interrelationship with terphenylquinones, xylerythrins and pulvinic acids. Tetrahedron Lett 1987, 28, 4, 4749. |
| 【2】 Pattenden, G.; et al.; Synthesis of grevillins, novel pyrandione pigments of fungi. Biogenetic ibnterrelationships between grevillins, pulvinic acids, terphenylquinones and xylerythrins. J Chem Soc - Perkins Trans I 1991, 2363. |
| 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) | 18456 | 2-phenylacetaldehyde | 122-78-1 | C8H8O | 详情 | 详情 |
| (II) | 18457 | 3-phenyl-2-[(trimethylsilyl)oxy]propanenitrile | C12H17NOSi | 详情 | 详情 | |
| (III) | 18458 | 3-hydroxy-1,4-diphenyl-2-butanone | C16H16O2 | 详情 | 详情 | |
| (IV) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
| (V) | 18460 | 1-benzyl-2-oxo-3-phenylpropyl 2-ethoxy-2-oxoacetate | C20H20O5 | 详情 | 详情 | |
| (VI) | 18461 | 6-benzyl-3-hydroxy-4-phenyl-2H-pyran-2,5(6H)-dione | C18H14O4 | 详情 | 详情 | |
| (VII) | 18462 | 6-benzyl-3-methoxy-4-phenyl-2H-pyran-2,5(6H)-dione | C19H16O4 | 详情 | 详情 | |
| (VIII) | 18463 | 6-benzyl-6-bromo-3-methoxy-4-phenyl-2H-pyran-2,5(6H)-dione | C19H15BrO4 | 详情 | 详情 | |
| (IX) | 18464 | 3-methoxy-4-phenyl-6-[(Z)-benzylidene]-2H-pyran-2,5-dione | C19H14O4 | 详情 | 详情 | |
| (X) | 18465 | 3-hydroxy-4-phenyl-6-[(Z)-benzylidene]-2H-pyran-2,5-dione | C18H12O4 | 详情 | 详情 | |
| (XI) | 18466 | 2,5-dihydroxy-3,6-diphenylbenzo-1,4-quinone | 548-59-4 | C18H12O4 | 详情 | 详情 |
| (XII) | 16143 | 3-(4-iodobutyl)-1-[[(E)-benzylidene]amino]-1H-imidazole-2,4(3H,5H)-dione | C14H16IN3O2 | 详情 | 详情 |