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【结 构 式】 
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【药物名称】Carprofen, Ro-20-5720, C-5720, Rimadyl, Imadyl 【化学名称】(±)-6-Chloro-alpha-methylcarbazole-2-acetic acid 【CA登记号】53716-49-7 【 分 子 式 】C15H12ClNO2 【 分 子 量 】273.72139 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The condensation of cyclohexenone (I) with diethyl alpha-methylmalonate (II) by means of sodium ethoxide in ethanol gives diethyl alpha-methyl-3-oxocyclohexanemalonate (III), oil b.p.(0.8) = 149-52 C, n(20)(D) = 1.4660, which is hydrolyzed and decarboxylated with refluxing dioxane-HCl to yield alpha-methyl-3-oxocyclohexaneacetic acid (IV), oil, b.p.(0.7) = 164-6 C, n(20)(D) = 1.4794. The condensation of (IV) with 4-chlorophenylhydrazine (A) in acetic acid-water atfords 6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetic acid (V), m.p. 193-202 C, which is esterified with ethanol-HCl to ethyl 6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetate (VI) and aromatized with chloranil (B) in refluxing xylene to give ethyl 6-chloro-alpha-methylcarbazole-2-acetate (VII), m.p. 106.0-7.5 C. Finally, this ester is hydrolyzed with NaOH in refluxing ethanol.
| 【1】 Berger, L.; Corraz, A.J.; Carbazoles. ES 417167; ES 442684; ES 442685; US 3896145 . |
| 【2】 Weetman, D.F.; Castaner, J.; Carprofen. Drugs Fut 1977, 2, 1, 15. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 21891 | 2,3,5,6-Tetrachloro-1,4-benzoquinone; 2,3,5,6-Tetrachlorobenzo-1,4-quinone; p-Chloranil | 118-75-2 | C6Cl4O2 | 详情 | 详情 |
| (A) | 33345 | 1-(4-chlorophenyl)hydrazine; 4-Chlorophenylhydrazine | 1073-70-7 | C6H7ClN2 | 详情 | 详情 |
| (I) | 26253 | 2-cyclohexen-1-one；Cyclohex-2-enone；2-cyclohexenone | 930-68-7 | C6H8O | 详情 | 详情 |
| (II) | 30310 | diethyl 2-methylmalonate | 609-08-5 | C8H14O4 | 详情 | 详情 |
| (III) | 33625 | diethyl 2-methyl-2-(3-oxocyclohexyl)malonate | C14H22O5 | 详情 | 详情 | |
| (IV) | 33626 | 2-(3-oxocyclohexyl)propionic acid | C9H14O3 | 详情 | 详情 | |
| (V) | 33627 | 2-(6-chloro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)propionic acid | C15H16ClNO2 | 详情 | 详情 | |
| (VI) | 33628 | ethyl 2-(6-chloro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)propanoate | C17H20ClNO2 | 详情 | 详情 | |
| (VII) | 33629 | ethyl 2-(6-chloro-9H-carbazol-2-yl)propanoate | C17H16ClNO2 | 详情 | 详情 |