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【结 构 式】 
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【分子编号】50013 【品名】2,4-dichloro-5-methoxyphenylamine; 2,4-dichloro-5-methoxyaniline 【CA登记号】 |
【 分 子 式 】C7H7Cl2NO 【 分 子 量 】192.04412 【元素组成】C 43.78% H 3.67% Cl 36.92% N 7.29% O 8.33% |
合成路线1
该中间体在本合成路线中的序号：(XI)Alkylation of 4-hydroxy-5-methoxy benzoic acid methyl ester (I) with 3-chloropropyl p-toluene sulfonate (III) by means of K2CO3 and methyl-tricapryl ammonium chloride (Aliquat 128) in refluxing acetone affords compound (III), which is then nitrated by means of HNO3 in HOAc to furnish 2-nitro derivative (IV). Reduction of the nitro moiety of (IV) by means of Fe in H2O/MeOH in the presence of ammonium chloride yields 2-amino compound (V), which is subjected to reaction with refluxing dimethylformamide dimethylacetal (VI) to provide amidine (VII). Condensation of (VII) with acetonitrile by means of n-BuLi in hexane/THF/HOAc gives substituted quinoline-carbonitrile (IX), whose hydroxyl group is replaced by a chlorine by treatment of (IX) with refluxing POCl3 to afford compound (X). Coupling of (X) with 2,4-dichloro-5-methoxyaniline (XI) in 2-ethoxyethanol in the presence of pyridine hydrochloride yields compound (XII), which is finally converted into the desired compound by condensation with 1-methylpiperazine (XII) by means of NaI in refluxing ethylene glycol dimethyl ether.
| 【1】 Boschelli, D.H.; Ye, F.; Wang, Y.D.; Dutia, M.; Johnson, S.L.; Wu, B.; Miller, K.; Powell, D.W.; Yaczko, D.; Young, M.; Tischler, M.; Arndt, K.; Discafani, C.; Etienne, C.; Gibbons, J.; Grod, J.; Lucas, J.; Weber, J.M.; Boschelli, F.; Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem 2001, 44, 23, 3965. |
| 【2】 Boschelli, D.H.; Dutia, M.; Ye, F.; et al.; Inhibition of SRC kinase activity by 4-phenylamino-3-quinolinecarbonitriles Part 2: Optimization of the side chain at C-7. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 145. |
| 【3】 Boschelli, D.H.; Wang, Y.D.; Ye, F.; et al.; Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles. J Med Chem 2001, 44, 5, 822. |
| 【4】 Tsou, H.-R.; Wissner, A.; Johnson, B.D.; Reich, M.F.; Floyd, M.B. Jr.; Kitchen, D.B. (American Cyanamid Co.); Substituted 3-cyano quinolines. US 6002008 . |
| 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) | 29176 | methyl 4-hydroxy-3-methoxybenzoate | 3943-74-6 | C9H10O4 | 详情 | 详情 |
| (II) | 19490 | 3-chloro-1-propanol | 627-30-5 | C3H7ClO | 详情 | 详情 |
| (III) | 50008 | methyl 4-(3-chloropropoxy)-3-methoxybenzoate | C12H15ClO4 | 详情 | 详情 | |
| (IV) | 50009 | methyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate | C12H14ClNO6 | 详情 | 详情 | |
| (V) | 50010 | methyl 2-amino-4-(3-chloropropoxy)-5-methoxybenzoate | C12H16ClNO4 | 详情 | 详情 | |
| (VI) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (VII) | 50011 | methyl 4-(3-chloropropoxy)-2-[[(E)-(dimethylamino)methylidene]amino]-5-methoxybenzoate | C15H21ClN2O4 | 详情 | 详情 | |
| (VIII) | 37210 | acetonitrile | 75-05-8 | C2H3N | 详情 | 详情 |
| (IX) | 50012 | 7-(3-chloropropoxy)-4-hydroxy-6-methoxy-3-quinolinecarbonitrile | C14H13ClN2O3 | 详情 | 详情 | |
| (X) | 48519 | 4-chloro-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile | C14H12Cl2N2O2 | 详情 | 详情 | |
| (XI) | 50013 | 2,4-dichloro-5-methoxyphenylamine; 2,4-dichloro-5-methoxyaniline | C7H7Cl2NO | 详情 | 详情 | |
| (XII) | 50014 | 7-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-3-quinolinecarbonitrile | C21H18Cl3N3O3 | 详情 | 详情 | |
| (XIII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |