新产品编号:421321
Chemical Name: N-[2-[N-[4-Chloro-2-cyano-3-(2-methylquinolin-8-yloxymethyl)phenyl]-N-methylamino]-2-oxoethyl]-3-methoxycinnamamide
CAS No. 213987-32-7
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Fused N-heterocyclic cpds.substd.with benzyloxy,process for their preparation and their use as bradykinin receptor antagonists
文献作者:Heitsch,H.; Wirth,K.; Sch鰈kens,B.; Wagner,A.(Aventis SA)
参考来源:DE 19712960; EP 0867432; JP 1998279563
📄 详细内容
合成路线: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.
参考文献标题:Novel series of O-substituted 8-quinolines and 4-benzothiazoles as potent antagonists of the bradykinin B2 receptors
文献作者:Heitsch,H.; Wagner,A.; Scholkens,B.A.; Wirth,K.
参考来源:Bioorg Med Chem Lett 1999,9(3),327