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【结 构 式】 
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【药物名称】A-295339 【化学名称】5-[4-[3-(4-Acetylpiperazin-1-yl)-3-oxo-1-propenyl]-2-chlorophenylsulfanyl]-1-methyl-1H-indole 【CA登记号】280750-58-5 【 分 子 式 】C24H24ClN3O2S 【 分 子 量 】453.99478 |
【开发单位】Abbott (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Antiarthritic Drugs, Asthma Therapy, RESPIRATORY DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Anti-ICAM-1 Agents, Cell Adhesion Inhibitors |
合成路线1
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 |