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【结 构 式】 
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【分子编号】38277 【品名】4,7-dichloroquinoline 【CA登记号】86-98-6 |
【 分 子 式 】C9H5Cl2N 【 分 子 量 】198.05084 【元素组成】C 54.58% H 2.54% Cl 35.8% N 7.07% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of 2-propylphenol (I) first with NaNO2/AcOH, then with Na2S2O4 and finally with acetic anhydride gives the acetamide (II), which is treated with formaldehyde and tert-butylamine in ethanol yielding the tert-butylaminomethyl derivative (III). The hydrolysis of (III) with 6M HCl affords the aminophenol (IV), which is finally condensed with 4,7-dichloroquinoline (V) in refluxing ethanol.
| 【1】 Raynes, K.J.; Stocks, P.A.; Ward, S.A.; O'Neill, P.M.; Park, B.K.; New 4-aminoquinoline mannich base antimalarials. 1. Effect of an alkyl substituent in the 5'-position of the 4'-hydroxyanilino side chain. J Med Chem 1999, 42, 15, 2747. |
| 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) | 38273 | 2-propylphenol | 644-35-9 | C9H12O | 详情 | 详情 |
| (II) | 38274 | N-(4-hydroxy-3-propylphenyl)acetamide | C11H15NO2 | 详情 | 详情 | |
| (III) | 38275 | N-[3-[(tert-butylamino)methyl]-4-hydroxy-5-propylphenyl]acetamide | C16H26N2O2 | 详情 | 详情 | |
| (IV) | 38276 | 4-amino-2-[(tert-butylamino)methyl]-6-propylphenol | C14H24N2O | 详情 | 详情 | |
| (V) | 38277 | 4,7-dichloroquinoline | 86-98-6 | C9H5Cl2N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The reaction of 2-isopropylphenol (I) first with NaNO2/AcOH, then with Na2S2O4 and finally with acetic anhydride gives the acetamide (II), which is treated with formaldehyde and tert-butylamine in ethanol yielding the tert-butylaminomethyl derivative (III). The hydrolysis of (III) with 6M HCl affords the aminophenol (IV), which is finally condensed with 4,7-dichloroquinoline (V) in refluxing ethanol.
| 【1】 Raynes, K.J.; Stocks, P.A.; Ward, S.A.; O'Neill, P.M.; Park, B.K.; New 4-aminoquinoline mannich base antimalarials. 1. Effect of an alkyl substituent in the 5'-position of the 4'-hydroxyanilino side chain. J Med Chem 1999, 42, 15, 2747. |
| 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) | 37653 | 2-isopropylphenol | 88-69-7 | C9H12O | 详情 | 详情 |
| (II) | 38278 | N-(4-hydroxy-3-isopropylphenyl)acetamide | C11H15NO2 | 详情 | 详情 | |
| (III) | 38279 | N-[3-[(tert-butylamino)methyl]-4-hydroxy-5-isopropylphenyl]acetamide | C16H26N2O2 | 详情 | 详情 | |
| (IV) | 38280 | 4-amino-2-[(tert-butylamino)methyl]-6-isopropylphenol | C14H24N2O | 详情 | 详情 | |
| (V) | 38277 | 4,7-dichloroquinoline | 86-98-6 | C9H5Cl2N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Condensation of 1,4,7-triazacyclononane (I) with 4,7-dichloroquinoline (II) produced the disubstituted derivative (III). Then, coupling of glutaric acid (IV) with amine (III) using bromo-tris-pyrrolidinophosphonium hexafluorophosphate gave the corresponding diamide.
| 【1】 Girault, S.; Grellier, P.; Sergheraert, C.; Lemière, P.; Maes, L.; Davioud-Charvet, E.; Berceibar, A.; Mouray, E.; Antiplasmodial activity and cytotoxicity of bis-, tris-, and tetraquinolines with linear or cyclic amino linkers. J Med Chem 2001, 44, 11, 1658. |
| 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) | 50898 | Octahydro-1H-1,4,7-triazonine; 1,4,7-Triazacyclononane; Triethylenetriamine | 4730-54-5 | C6H15N3 | 详情 | 详情 |
| (II) | 38277 | 4,7-dichloroquinoline | 86-98-6 | C9H5Cl2N | 详情 | 详情 |
| (III) | 50899 | 7-chloro-4-[4-(7-chloro-4-quinolinyl)-1,4,7-triazonan-1-yl]quinoline | C24H23Cl2N5 | 详情 | 详情 | |
| (IV) | 50900 | Pentanedioic Acid; 1,5-Pentanedioic acid; 1,3-Propanedicarboxylic acid; Glutaric acid | 110-94-1 | C5H8O4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The intermediate anilinoquinoline (III) was obtained by nucleophilic substitution of 4,7-dichloroquinoline (II) with 3,5-diaminobenzyl alcohol (I) in the presence of N-methylmorpholine. Coupling of (III) with chloroacetic acid gave the corresponding chloroacetamide (IV), which was further reacted with piperidine in DMF, yielding the piperidino acetamide (V). The benzyl alcohol function of (V) was then oxidized to aldehyde (VI) employing manganese dioxide. Finally, reductive condensation of aldehyde (VI) with morpholine in the presence of NaBH(OAc)3 furnished the title compound.
| 【1】 Delareu, S.; et al.; Synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines. J Med Chem 2001, 44, 17, 2827. |
| 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) | 51039 | (3,5-diaminophenyl)methanol | C7H10N2O | 详情 | 详情 | |
| (II) | 38277 | 4,7-dichloroquinoline | 86-98-6 | C9H5Cl2N | 详情 | 详情 |
| (III) | 51040 | [3-amino-5-[(7-chloro-4-quinolinyl)amino]phenyl]methanol | C16H14ClN3O | 详情 | 详情 | |
| (IV) | 51041 | 2-chloro-N-[3-[(7-chloro-4-quinolinyl)amino]-5-(hydroxymethyl)phenyl]acetamide | C18H15Cl2N3O2 | 详情 | 详情 | |
| (V) | 51042 | N-[3-[(7-chloro-4-quinolinyl)amino]-5-(hydroxymethyl)phenyl]-2-(1-piperidinyl)acetamide | C23H25ClN4O2 | 详情 | 详情 | |
| (VI) | 51043 | N-[3-[(7-chloro-4-quinolinyl)amino]-5-formylphenyl]-2-(1-piperidinyl)acetamide | C23H23ClN4O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VI)The (dimethylaminomethyl)ferrocene (I) was metalated with butyllithium and the organolithium intermediate (II) was condensed with dimethylformamide to furnish, after aqueous quenching, the ferrocenecarboxaldehyde (III). Aldehyde (III) was converted to oxime (IV) by treatment with hydroxylamine in aqueous ethanol. Reduction of oxime (IV) using LiAlH4 produced the primary amine (V). This was then condensed with 4,7-dichloroquinoline (VI) in hot NMP, and the resulting adduct was finally isolated as the L-tartrate salt.
| 【1】 Domarle, O.; et al.; In vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine. Antimicrob Agents Chemother 1998, 42, 3, 540. |
| 【2】 Biot, C.; et al.; Synthesis an antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue. J Med Chem 1997, 40, 23, 3715. |
| 【3】 Lebibi, J.; Brocard, J.; Maciejewski, L. (Université des Sciences et Technologies de Lille - Lille 1); Antimalarial organometallic iron complexes. WO 9635698 . |