巴洛沙星合成研究.pdfVIP

响，确立了合成及精制Q-35的优化工艺:做薄层色谱((TLC)跟踪反应 进程，确定了最佳反应时间5h，用高压液相色谱(HPLC)法对Q-35进 行含量分析，确立了反应温度为60C，以乙睛作为反应溶剂，Q-35 的含量为85.71 ;精品Q-35的含量为90.62 ，同时对精制品进行 紫外吸收光谱(UV)、元素分析、红外吸收光谱((FT-IR)、核磁共振氢 谱(IH-NMR)、核磁共振碳谱(13C-NMR)、质谱(MS)、热重分析(TG) 等表征，结果表明产品的化学结构与巴洛沙星实际的化学结构相符。 关键词:3一甲氨基呱睫，合成，重结晶，硼鳌合物，巴洛沙星 ABSTRACT Balofloxacin,l-cyclopropyl-6-fluoro-8-methoxy-7-f(3-methylamino) piperidin-1-yl]-4-oxo-1,4-dihydro-3-quinolinecarboxylicaciddehydrates, isoneofthenewfluoroquinolones,whichhadbeensynthesizedby NaganoHheChugaiPharmaceuticalcompanyofJapanandhad beenphasedIIIin1999.Thisproducthasnotbeenmarketedand produceddomesticallyinthistime.Thesynthesisofintermediateof 3-methylaminopiperidinerfom3-aminopyridineasrawmaterialandthe synthesisofBalofloxacinrfomDFQ-Etbymeansoftheboratechelate weredeeplystudiedinthispaper.Alltheseworkwillcontributetothe newsynthesisofBalofloxacin,especiallythestudyonthesynthesisof boratechelate. Theoptimumreactionconditionswerestudiedduringtheprotection oftheaminogroupatthe3-positionof3-aminopyridine.The 3-aminopyridinewasaddedslowlytothemixtureofp-toluenesulfonyl chlorideandpyridine.The3-(p-toluenesulfonylamino)pyridinewas obtainedwiththeyieldof91.2% for2h,characterizedbytheTLC spectra.Therecrystallizationof3-p(-Toluenesulfonylamino)pyridinewas obtainedwiththeyieldof87.3% bytheuseof80% ethanolas recrystlingsolvent;m.p.192.6-193.40C.WiththemolarratioofNaOH to3-p(-toluenesulfonylamino)pyridinebeing7:1andthemolarratioof 3-(p-toluenesulfonylamino)pyridinetoMe2SO4being 1:2.1,the 3N,3N-(methylp-toluenesulfonylamino)pyridinewasobtainedwiththe yieldof49.5%. TheDFQ-B(OAc)2wasobtainedwiththeyieldof90.4% for3hat 900C,washedwithwater,thendriedupat450Cunderreducedpressure of一0.065MPa,beingthepurityof98.00%,ThesynthesisofQ-35was carriedoutat600Cfor5hwithCH3CNbeingsolvent,beingthepurityof 85.71%.TherefinedQ-35wasobtainedwiththepurityof90.62%, characterizedbytheTLCspectraandtheHPLCspectra.Therefined pr