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【结 构 式】 
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【分子编号】18122 【品名】3,4-Dichlorobenzaldehyde 【CA登记号】6287-38-3 |
【 分 子 式 】C7H4Cl2O 【 分 子 量 】175.01356 【元素组成】C 48.04% H 2.3% Cl 40.51% O 9.14% |
合成路线1
该中间体在本合成路线中的序号：(II)The arylation of 4-phenylphenol (I) with 3,4-dichlorobenzaldehyde (II) in the presence of K2CO3 in hot DMSO afforded diary ether (III). The target carboxylic acid was then obtained by oxidation of the aldehyde group of (III) by means of Ag2O, generated from AgNO3 and NaOH.
| 【1】 Fujii, M.; Naito, R.; Oritani, H.; Kimura, T.; Koutoku, H.; Hara, H.; Igarashi, S.; Mase, T.; A novel class of inhibitors for human steroid 5alpha-reductase: Phenoxybenzoic acid derivatives. I. Chem Pharm Bull 1999, 47, 8, 1073. |
合成路线2
该中间体在本合成路线中的序号：(I)Aldol condensation between 3,4-dichlorobenzaldehyde (I) and 4'-hydroxyacetophenone (II) in hydroalcoholic NaOH yielded chalcone (III). Then, Mannich reaction of (III) with N,N-dimethylmethyleneammonium chloride (IV) in refluxing acetonitrile provided the bis(dimethylamino) compound as the dihydrochloride.
| 【1】 Dimmock, J.R.; et al.; Cytotoxic activities of Mannich bases of chalcones and related compounds. J Med Chem 1998, 41, 7, 1014-1026. |
| 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) | 18122 | 3,4-Dichlorobenzaldehyde | 6287-38-3 | C7H4Cl2O | 详情 | 详情 |
| (II) | 18123 | 1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone | 99-93-4 | C8H8O2 | 详情 | 详情 |
| (III) | 18124 | (E)-3-(3,4-dichlorophenyl)-1-(4-hydroxyphenyl)-2-propen-1-one | C15H10Cl2O2 | 详情 | 详情 | |
| (IV) | 18125 | dimethyl(methylene)-lambda(5)-azane | C3H9N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Reaction of 3,4-dichlorobenzalzehyde (I) with methyl 3-mercaptopropionate in the presence of K2CO3 in hot DMF afforded the thioether (II). Subsequent condensation of (II) with malonic acid under Knoevenagel conditions produced the substituted cinnamic acid (III), which was further converted to the corresponding acid chloride (IV) upon treatment with oxalyl chloride and a catalytic amount of DMF. Coupling of acid chloride (IV) with N-acetylpiperazine (V) furnished amide (VI). Treatment of (VI) with potassium tert-butoxide caused the elimination of methyl acrylate, producing the potassium thiolate (VII). Thiolate (VII) was then condensed with 1-methyl-7-bromoindole (VIII) to give the title compound.
| 【1】 Lynch, J.K.; Link, J.; Zhu, G.-D.; Boyd, S.A.; Winn, M.; Pei, Z.; Gunawardana, I.W.; Liu, G.; Xin, Z.; Jae, H.-S.; Freeman, J.C.; Von Geldern, T.; Staeger, M.A. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. US 6110922; WO 0039081 . |
| 【2】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 . |
| 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) | 18122 | 3,4-Dichlorobenzaldehyde | 6287-38-3 | C7H4Cl2O | 详情 | 详情 |
| (II) | 48173 | methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate | C11H11ClO3S | 详情 | 详情 | |
| (III) | 48174 | (E)-3-[3-chloro-4-[(3-methoxy-3-oxopropyl)sulfanyl]phenyl]-2-propenoic acid | C13H13ClO4S | 详情 | 详情 | |
| (IV) | 48175 | methyl 3-([2-chloro-4-[(E)-3-chloro-3-oxo-1-propenyl]phenyl]sulfanyl)propanoate | C13H12Cl2O3S | 详情 | 详情 | |
| (V) | 20674 | N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone | 13889-98-0 | C6H12N2O | 详情 | 详情 |
| (VI) | 48176 | methyl 3-([4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorophenyl]sulfanyl)propanoate | C19H23ClN2O4S | 详情 | 详情 | |
| (VII) | 48177 | potassium 4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorobenzenethiolate | C15H16ClKN2O2S | 详情 | 详情 | |
| (VIII) | 29521 | 5-bromo-1-methyl-1H-indole | C9H8BrN | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)It is prepared through the following sequence: The Strecker reaction of 3,4-dichlorobenzaldehyde (I) with sodium cyanide and NH4Cl affords alpha-amino-3,4-dichlorophenylacetonitrile (II) (HCl salt, m.p. 184-5 C), which is reduced with LiAlH4 to 2-amino-1-(3',4'-dichlorophenyl)ethylamine (III) (di HCl salt, m.p. 283-5 C). Finally compound (III) is cyclized with BrCN in benzene.
| 【1】 Castaner, J.; Blancafort, P.; M J 10459 - 2. Drugs Fut 1976, 1, 5, 250. |
| 【2】 Mathier, W.L.; et al.; 9-Cis retinoic acid enhances the effectiveness of PPARgamma-specific agonists in non-small cell lung cancer (NSCLC) cell lines. J Med Chem 1973, 16, 901. |