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【结 构 式】 
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【分子编号】29528 【品名】6-amino-3-chloro-2-[[(2-methyl-8-quinolinyl)oxy]methyl]benzonitrile 【CA登记号】 |
【 分 子 式 】C18H14ClN3O 【 分 子 量 】323.78148 【元素组成】C 66.77% H 4.36% Cl 10.95% N 12.98% O 4.94% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2,6-dichloro-3-nitrotoluene (I) with CuCN in hot DMF gives the benzonitrile (II), which is brominated with 1,3-dibromo-5,5-dimethylhidantoin (DBDH) and benzoyl peroxide in hot chlorobenzene yielding the benzyl bromide (III). The reaction of (III) with 2-methyl-8-quinolinol (IV) by means of K2CO3 or Cs2CO3 in DMF affords the benzyl ether (V), which is reduced at the nitro group with SnCl2 giving the amino derivative (VI). The condensation of (VI) with 2-phthalimidoacetyl chloride (VII) by means of DMAP and pyridine in refluxing dichloromethane yields the corresponding amide (VIII), which is N-methylated with methyl iodide and NaH in DMF affording intermediate (IX). Elimination of the phthalimido group of (IX) with hydrazine in refluxing dichloromethane/methanol provides the substituted glycinamide (X), which is finally acylated with 3-(3-methoxyphenyl)-2(E)-propenoyl chloride (XI) by means of triethylamine in refluxing dichloromethane.
| 【1】 Scholkens, B.A.; Heitsch, H.; Eagner, A.; Wirth, K.; Novel series of O-substituted 8-quinolines and 4-benzothiazoles as potent antagonists of the bradykinin B2 receptors. Bioorg Med Chem Lett 1999, 9, 3, 327. |
| 【2】 Heitsch, H.; Wirth, K.; Scholkens, B.; Wagner, A. (Aventis SA); Fused N-heterocyclic cpds. substd. with benzyloxy, process for their preparation and their use as bradykinin receptor antagonists. DE 19712960; EP 0867432; JP 1998279563 . |
| 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) | 29524 | 1,3-dichloro-2-methyl-4-nitrobenzene | 29682-46-0 | C7H5Cl2NO2 | 详情 | 详情 |
| (II) | 29525 | 3-chloro-2-methyl-6-nitrobenzonitrile | C8H5ClN2O2 | 详情 | 详情 | |
| (III) | 29526 | 2-(bromomethyl)-3-chloro-6-nitrobenzonitrile | C8H4BrClN2O2 | 详情 | 详情 | |
| (IV) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (V) | 29527 | 3-chloro-2-[[(2-methyl-8-quinolinyl)oxy]methyl]-6-nitrobenzonitrile | C18H12ClN3O3 | 详情 | 详情 | |
| (VI) | 29528 | 6-amino-3-chloro-2-[[(2-methyl-8-quinolinyl)oxy]methyl]benzonitrile | C18H14ClN3O | 详情 | 详情 | |
| (VII) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (VIII) | 29529 | N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C28H19ClN4O4 | 详情 | 详情 | |
| (IX) | 29530 | N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C29H21ClN4O4 | 详情 | 详情 | |
| (X) | 29531 | 2-amino-N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C21H19ClN4O2 | 详情 | 详情 | |
| (XI) | 29532 | (E)-3-(3-methoxyphenyl)-2-propenoyl chloride | C10H9ClO2 | 详情 | 详情 |