“一锅法”合成帕珠沙星中间体

以(S)-10-氰甲基-9-氟-3-甲基-7-氧代-3,7-二氢-2H-1,4]-口恶嗪2,3,4-ij]喹啉-6-羧酸乙酯(Ⅱ)为原料,经环合、水解"一锅法"反应,制备帕珠沙星高级中间体(S)-10-(1-环丙基甲酰胺)-9-氟-3-甲基-7-氧代-3,7-二氢-2H-1,4]-口恶嗪2,3,4-ij]喹啉-6-羧酸(Ⅳ),探讨了温度、碱、溶剂等对反应的影响。确定较佳的合成工艺条件为:n(化合物Ⅱ):n(1,2-二氯乙烷):n(苄基三乙基氯化铵):n(氢氧化钠)=1:1.5:0.43:16.7,水作为溶剂,先室温搅拌5 h,随后加热到70℃反应2 h,收率达82%。

Synthesis of Intermediate of Pazufloxacin by One-pot Reaction

(S)-10-(1-carbamoylcyclopropyl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H——oxazino2,3,4-ij]quinoline-6-carboxylic acid,the senior intermediate of pazu-floxacin,was synthesiszed from(S)-ethyl 10-(cyanomethyl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-oxazino2,3,4-ij]quinoline-6-carboxylate via a one-pot reaction of cyclopropanation and cyanide hydrolyzation.The reaction conditions were optimized as follows:n(compound Ⅱ):n(1,2-dichloroethane):n(benzyltriethylammonium chloride):n(NaOH)=1:1.5:0.43:16.7,stirred in water for 5 h at room temperature and then at 70 ℃ for 2 h.Under such optimum conditions,the yield of the product was 82%.The method has the advantages of mild reaction conditions,safety,low cost,and environment-friendliness.