帕珠沙星注册杂质合成研究
毕业论文关键词：帕珠沙星；合成；当量；B-4；P-3；D-9
Sign Pazufloxacin synthesis of impurities
Abstract: pazufloxacin is now widely used on the market fourth generation quinolone antibacterial drugs, this paper analyzes two kinds of impurities may arise in production process, and established a series of chemical method synthesis of several impurities. Get the right amount of samples, to provide raw materials and the scientific basis for the next step research. The reaction solvent, reactant equivalent and equivalent, reaction temperature, additives and equivalent and reaction system and the reaction condition were studied, the optimum process conditions of choice. B-4 ((S) -9- -10- (f 1- acetyl imine cyclopropyl) -3- methyl -2,3- two hydrogen -7- oxo -7H- pyridine and [1,2,3-de] [1,4] benzoxazine -6- carboxylic acid): pazufloxacin as raw material, using pyridine as solvent, acetic anhydride using 6 equivalent, temperature control at 60 ± 2 ℃, stirring reaction time is 16 hours, the experiment according to these conditions, the yield of B-4 optimal up to 80.6%. P-3 ((S) -9- -3- -2,3- two fluoro -10- carboxyl methyl hydrogen -7- oxo -7H- pyridine and [1,2,3-de] [1,4] benzoxazine -6- carboxylic acid ethyl ester): with P-2 as raw material, using DMF (two methyl formamide) as a reaction solvent, solid sodium cyanide with 2 equivalent, temperature control at 80 ± 2 ℃, mixing reaction time mix for 10 hours, do not add alkali, the experiments according to this condition, the yield of P-3 optimal up to 60.3%. D-9 ((S) -9- -3- -2,3- two fluoro -10- carboxyl methyl hydrogen -7- oxo -7H- pyridine and [1,2,3-de] [1,4] benzoxazine -6- carboxylic acid): with P-3 as raw material, the use of ethanol as solvent, using NaOH solution (1mol/L, 5 equivalents), temperature 2 ℃ ~100 ± 2 ℃ at 90 ±, stirring under the reaction time of 5 hours, the experiment according to these conditions, the yield of D-9 optimal up to 89.3%.
Keywords: Paper Shah Singh; synthesis; equivalence; B-; P-3; D-9
目录
1 绪论 1
1.1 本课题国内外研究现状概述 1
1.1.1 甲磺酸帕珠沙星简介 1
1.1.2 帕珠沙星合成工艺 1
1.1.3 帕珠沙星的抗菌机制及优势 2
1.2 喹诺酮类药物 3
1.2.1 喹诺酮药物概述 3
1.3 合成实验中常用提纯方法和检测方法 4
1.3.1 减压蒸馏 4