当前位置: 首页 » 资料 » 医药中间体库 » ,C12H11ClN2O4,282.6855,5-chloro-2,6-dimethoxy-4-methyl-8-nit

,C12H11ClN2O4,282.6855,5-chloro-2,6-dimethoxy-4-methyl-8-nit

放大字体  缩小字体 更新日期:2018-11-23  浏览次数:6
摘 要:,C12H11ClN2O4,282.6855,5-chloro-2,6-dimethoxy-4-methyl-8-nitroquinoline; 5-chloro-2-methoxy-4-methyl-8-nitro-6-quinolinyl methyl ether
  • 【化学名】5-chloro-2,6-dimethoxy-4-methyl-8-nitroquinoline; 5-chloro-2-methoxy-4-methyl-8-nitro-6-quinolinyl methyl ether
  • 【CAS登记号】
  • 【结构式】,C12H11ClN2O4,282.6855,5-chloro-2,6-dimethoxy-4-methyl-8-nit--药物合成数据库
  • 【分子式】C12H11ClN2O4
  • 【分子量】282.6855
  • 【来源】
  • 【合成情况】 
  • 〖目标产物〗Tafenoquine succinate, Etaquine, SB-252263, WR-238605
  • 〖合成路线〗
  • 〖合成方法〗Reaction of 4-methoxyaniline (XXI) with ethyl acetoacetate (XXII) by means of triethanolamine in refluxing xylene gives the acetoacetanilide (XXIII), which is cyclized by means of hot triethanolamine and H2SO4 to yield 6-methoxy-4-methylquinolin-2(1H)-one (I), which is treated with refluxing POCl3 to provide 2-chloro-6-methoxy-4-methylquinoline (XXIV). Reaction of compound (XXIV) with SO2Cl2 in hot AcOH affords 2,5-dichloro-6-methoxy-4-methylquinoline (XXV), which is treated with MeONa in refluxing methanol to furnish 5-chloro-2,6-dimethoxy-4-methylquinoline (XXVI). Alternatively, the reaction of compound (XXIV) with MeONa as before gives 2,6-dimethoxy-4-methylquinoline (XXVII), which is treated with SO2Cl2 in hot AcOH to give the already described 5-chloro-2,6-dimethoxy-4-methylquinoline (XXVI). Nitration of compound (XXVI) with KNO3 and P2O5 gives the 8-nitroquinoline derivative (XXVIII), which is condensed with 3-(trifluoromethyl)phenol (IV) by means of KOH in hot NMP to yield the diaryl ether (VII). Finally, the nitro group of compound (VII) is reduced with hydrazine over Pd/C.
  • 〖参考〗McIntyre, J.A.; Castaer, J.; Bays, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859
  • 〖目标产物〗Tafenoquine succinate, Etaquine, SB-252263, WR-238605
  • 〖合成路线〗
  • 〖合成方法〗Reaction of 4-methoxyaniline (XXI) with ethyl acetoacetate (XXII) by means of triethanolamine in refluxing xylene gives the acetoacetanilide (XXIII), which is cyclized by means of hot triethanolamine and H2SO4 to yield 6-methoxy-4-methylquinolin-2(1H)-one (I), which is treated with refluxing POCl3 to provide 2-chloro-6-methoxy-4-methylquinoline (XXIV). Reaction of compound (XXIV) with SO2Cl2 in hot AcOH affords 2,5-dichloro-6-methoxy-4-methylquinoline (XXV), which is treated with MeONa in refluxing methanol to furnish 5-chloro-2,6-dimethoxy-4-methylquinoline (XXVI). Alternatively, the reaction of compound (XXIV) with MeONa as before gives 2,6-dimethoxy-4-methylquinoline (XXVII), which is treated with SO2Cl2 in hot AcOH to give the already described 5-chloro-2,6-dimethoxy-4-methylquinoline (XXVI). Nitration of compound (XXVI) with KNO3 and P2O5 gives the 8-nitroquinoline derivative (XXVIII), which is condensed with 3-(trifluoromethyl)phenol (IV) by means of KOH in hot NMP to yield the diaryl ether (VII). Finally, the nitro group of compound (VII) is reduced with hydrazine over Pd/C.
  • 〖参考〗Ugwuegbulam, C.O.; Foy, J.E. (GlaxoSmithKline Inc.; GlaxoSmithKline plc); Process for the preparation of anti-malarial drugs. US 6479660; WO 9713753
 
本文导航:
  • (1) ,C12H11ClN2O4,282.6855,5-chloro-2,6-dimethoxy-4-methyl-8-nit
  • 下一篇:鳖甲
  • 上一篇:暂无
 
[ 资料搜索 ]  [ 加入收藏 ]  [ 告诉好友 ]  [ 打印本文 ]  [ 关闭窗口 ]

 

 
推荐图文
推荐资料
热门关注