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【结 构 式】 
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【分子编号】33345 【品名】1-(4-chlorophenyl)hydrazine; 4-Chlorophenylhydrazine 【CA登记号】1073-70-7 |
【 分 子 式 】C6H7ClN2 【 分 子 量 】142.58776 【元素组成】C 50.54% H 4.95% Cl 24.86% N 19.65% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The condensation of aniline (I) with diethyl ethoxymethylenemalonate (II) by heating at 90 C gives diethyl anilinomethylenemalonate (III), which is cyclized to ethyl 4-hydroxyquinoline-3carboxylate (IV) by heating at 240 C in diphenyl ether-biphenyl. The reaction of (IV) with hot POCl3 affords ethyl-4-chloroquinoline-3-carboxylate (V), which is finally cyclized with 4-chlorophenylhydrazine (VIII) by heating at 105 C in xylene. (VIII) is prepared in the usual way starting from 4-chloroaniline (IX) by diazotation with NaNO2-HCl to 4-chlorophenyldiazonium chloride (X), and reduction with SnCl2-HCl.
| 【1】 Yokoyama, N.; US 4312870 . |
| 【2】 Yokoyama, N.; EP 0022078 . |
| 【3】 Ritter, B.; Yokoyama, N.; Neubert, A.D.; 2-Arylpyrazolo[4,3-c]quinolin-3-ones: A partial novel agonist and antagonist of benzodiazepines. J Med Chem 1982, 25, 4, 337-339. |
| 【4】 Castaner, J.; Blancafort, P.; Grau, M.; Serradell, M.N.; CGS-8216 and CGS-9896. Drugs Fut 1983, 8, 2, 99. |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (III) | 35953 | diethyl 2-(anilinomethylene)malonate | C14H17NO4 | 详情 | 详情 | |
| (IV) | 35954 | ethyl 4-hydroxy-3-quinolinecarboxylate | C12H11NO3 | 详情 | 详情 | |
| (V) | 35955 | ethyl 4-chloro-3-quinolinecarboxylate | C12H10ClNO2 | 详情 | 详情 | |
| (VIII) | 33345 | 1-(4-chlorophenyl)hydrazine; 4-Chlorophenylhydrazine | 1073-70-7 | C6H7ClN2 | 详情 | 详情 |
| (IX) | 12034 | 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline | 106-47-8 | C6H6ClN | 详情 | 详情 |
| (X) | 10197 | 4-Chlorobenzenediazonium chloride | C6H4Cl2N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(A)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 |
合成路线3
该中间体在本合成路线中的序号：(X)The reaction of o-fluorophenylpyruvate (I) with p-chlorophenylhydrazine (X) in refluxing ethanol gives ethyl o-fluorophenylpyruvate p-chlorophenylhydrazone (XI), which is cyclized by treatment with dry HCl in refluxing ethanol yielding ethyl 3-(2-fluorophenyl)-5-chloroindole-2-carboxylate (XII). The N-alkylation of (XII) with cyclopropylmethyl bromide (A) by means of KOH in refluxing acetone affords compound (IV) of the preceding sequence.
| 【1】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); Process for producing benzodiazepine derivatives. US 3632574 . |
| 【2】 Blancafort, P.; Serradell, M.N.; Castaner, J.; KB-509. Drugs Fut 1979, 4, 10, 720. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 22277 | Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane | 7051-34-5 | C4H7Br | 详情 | 详情 |
| (I) | 33337 | ethyl 3-(2-fluorophenyl)-2-oxopropanoate | C11H11FO3 | 详情 | 详情 | |
| (IV) | 33339 | ethyl 5-chloro-1-(cyclopropylmethyl)-3-(2-fluorophenyl)-1H-indole-2-carboxylate | C21H19ClFNO2 | 详情 | 详情 | |
| (X) | 33345 | 1-(4-chlorophenyl)hydrazine; 4-Chlorophenylhydrazine | 1073-70-7 | C6H7ClN2 | 详情 | 详情 |
| (XI) | 33346 | ethyl 2-[(E)-2-(4-chlorophenyl)hydrazono]-3-(2-fluorophenyl)propanoate | C17H16ClFN2O2 | 详情 | 详情 | |
| (XII) | 33347 | ethyl 5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxylate | C17H13ClFNO2 | 详情 | 详情 |