甲砜霉素甘氨酸酯盐酸盐的合成研究用电导率的方法测定α—卤 …

具有活性较强基团α－卤代羰基的化合物甲砜霉素氯乙酸酯和对硝基－α－溴代苯乙酮都能发生Ｄｅｌｅｐｉｎｅ反应，在此过程中，与乌洛托品成盐反应的前后电导率有显著的变化，因而可用电导率的测定证明其与洛托品形成盐，并且可利用测定电导变化跟踪反应过程与判断反应终点。     

微波促进Sommelet反应制备4-乙酰氧基-2-甲基-2-丁烯醛

1-氯-2-甲基-4-乙酰氧基-2-丁烯与乌洛托品成盐后水解，得到合成维生素A的重要中间体4-乙酰氧基-2-甲基-2-丁烯-1-醛，用微波辐射可促进水解，反应0．5h收率可达77％。     

甲砜霉素甘氨酸酯盐酸盐的合成

甲砜霉素甘氨酸酯盐酸盐增加了甲砜霉素的水溶性，可制成注射剂．其合成工艺是以甲砜霉素和氯乙酰氯为起始原料，经酰化、环六亚甲基（又称乌洛托品）成盐、水解及酸化成盐，合成了甲砜霉素甘氨酸酯盐酸盐     

甲砜霉素甘氨酸酯盐酸盐的合居

甲砜霉素甘氨酸酯盐酸盐增加了甲砜霉素的水溶性，可制成注制剂，其合成工艺是以甲砜霉素和氯乙酰氯为起始原料，经酰化、环六亚甲基（又称乌洛托品）成盐，水解及酸化成盐，合成了甲砜霉素甘氨酸酯盐酸盐。     

高效液相色谱法测定马尿酸乌洛托品片的有关物质

目的应用高效液相色谱法测定马尿酸乌洛托品片的有关物质。方法采用C18色谱柱(4.6mm×250mm,5μm),甲醇-乙腈-0.1%磷酸溶液(40∶25∶35)为流动相,流速:0.9mL/min,检测波长:217nm。结果在选定的色谱条件下,马尿酸乌洛托品与有关物质分离完全.最低检测限为30ng,精密度良好(RSD=0.78%)。结论该方法简便、准确、专属性好、灵敏度高,可用于马尿酸乌洛托品片的有关物质测定。     

乙酰磷酸二锂盐的制备及含量测定

目的制备乙酰磷酸二锂盐并对其进行含量测定。方法采用醋酐能迅速与磷酸盐生成乙酰磷酸盐 ,遇氢氧化锂可进一步反应生成乙酰磷酸二锂盐的方法 ;用羟肟酸与铁盐的呈色反应测定其含量。结果乙酰磷酸二锂盐的含量可达 80 %以上 ;收率可达 90 %以上。结论醋酐过量、氢氧化锂过量、在合成反应中增加搅拌的剧烈程度以及反应后期的低温环境 ,都是影响乙酰磷酸二锂盐收率的关键因素     

分光光度法测定乌洛托品的含量研究

依据乌洛托品紫外线吸收光谱选择 2 42 .0 nm作为测定波长 ,建立分光光度法测定了乌洛托品的含量。结果显示 ,乌洛托品浓度在 0 .1～ 12 .0μg.L- 1 之间呈良好的线性关系 ,相关系数 r=0 .9999( n=5 ) ,回收率为 99.67% ,RDS为 0 .2 3% ( n=5 )     

临床常见防腐剂对尿液电导率测定的影响

目的探讨临床常用防腐剂对尿液电导率测定的影响,以便在特殊情况下需要使用防腐剂防腐且需要测定电导率变化时选择对测定结果影响最小的防腐剂。方法用UF-1000i尿沉渣自动分析仪分别测定60例加了各种防腐剂尿液标本的即时及放置固定时间的尿液电导率。结果添加了甲苯和冰乙酸的尿液电导率无明显变化。添加了浓盐酸和甲醛的尿液电导率有明显变化。结论特殊情况下需要用添加防腐剂的尿液标本检测电导率时可选择甲苯和冰乙酸防腐。     

医院反渗透纯化水系统的数据模型

目的检测二级反渗透制备的质量。方法利用测定电导率的比值的方法。建立直线回归方程。结果透盐率增加与时间之间存在直线相关。结论快速、分析系统内部出现的故障原因。     

乌洛托品直肠栓的制备及生物利用度研究

乌洛托品是治疗泌尿系统感染的药物,但口服后易被胃酸破坏而影响疗效。本试验研制了乌洛托品直肠栓,其各项物理常数测定符合中国药典要求。生物利用度测定结果表明:栓剂的生物利用度高于口服液,从而避免了在胃中破坏,获得满意的结果。     

非布索坦的合成

对羟基苄腈与硫代乙酰胺反应得到4-羟基硫代苯甲酰胺,与2-氯乙酰乙酸乙酯环合后与六亚甲基四胺进行Duff反应得到2-(3-甲酰基-4-羟基苯基)-4-甲基-5-噻唑甲酸乙酯,再相继与盐酸羟胺/甲醇钠反应、异丁基溴成醚后碱性水解,制得抗痛风药非布索坦,总收率为28%.     

牛磺酸镁盐制备工艺的改进

目的研究牛磺酸镁盐的制备工艺,以提高产物收率。方法以酸碱中和反应合成牛磺酸镁盐,采用正交试验对制备工艺进行优选。结果改进后最佳工艺条件:反应温度80℃;反应时间5h;牛磺酸与氢氧化镁投料摩尔比2∶1(氢氧化镁略过量)。结论该工艺合理,操作简便,收率可达55%。     

对羟基苯乙酮衍生物的合成及其调节血脂活性研究

目的设计合成一系列对羟基苯乙酮衍生物,并测定其体内调节血脂活性。方法α-溴代对羟基苯乙酮分子中的溴原子被不同亲核试剂取代得到目标化合物A1～A4;α-溴代对羟基苯乙酮经Delepine反应、酰化反应得到目标化合物A5～A8;化合物A5～A7经氢氧化钠水解得到目标化合物A9～A11;1-叔丁氧基哌嗪与新戊酰氯缩合后,经三氟乙酸脱保护,再与α-溴代对羟基苯乙酮反应生成目标化合物A12。以对羟基苯乙酮、辛伐他汀、吉非罗齐为阳性对照药物,考察所合成化合物的调节血脂活性。结果与结论共合成了12个化合物,其中8个化合物为未见文献报道的新化合物,其结构经1H-NMR、MS谱确证。活性测试结果表明,化合物A5、A8的活性与阳性药相当,具有显著的同时降低低密度脂蛋白胆固醇和甘油三酯的活性,并且具有一定的升高高密度脂蛋白胆固醇的作用。     

Dehydration and rehydration of a hydrate diclofenac salt at room temperature.

The salt diclofenac/N-(2-hydroxyethyl) pyrrolidine crystallizes from water as a dihydrate, while it precipitates from organic solvents anhydrously: the two salts have different crystal structures. Dehydration of the dihydrate salt was carried out in a desiccator over silica gel at room temperature: the process occurs with the retention of the crystal structure. Slight changes observed in the diffractograms suggest, that soon after dehydration, a phase transition starts, slowly due to the low temperature of the process. The reaction was followed determining the loss of weight as a function of time and by thermal analysis, since the dihydrate and the dehydrate forms have different thermograms, but similar diffractograms. The reaction was complete after 24 h. The analysis of the experimental data suggests a kinetic process related to a one-dimensional diffusion of the crystallization water molecules outwards the solid particles. At room temperature, the dehydrate material rapidly back-absorbs the two molecules of crystallization water from the atmosphere moisture. The interaction with water of the different forms of the salt was discussed as a function of their solid structures as well as of the complex equilibria present in aqueous solution: these can explain previous apparently anomalous results. Copyright     

甲磺酸达氟沙星的合成工艺改进

目的研究甲磺酸达氟沙星的合成工艺.方法以反-4-羟基-L-脯氨酸为起始原料,经N-保护、还原、酰化、环合、脱保护、缩合、成盐7步反应得到甲磺酸达氟沙星.结果与结论该法操作简便,更有利于工业化生产,甲磺酸达氟沙星总收率达50%(以脯氨酸计).     

头孢尼西钠的合成方法改进

目的:研究头孢尼西钠的合成新工艺。方法:7-氨基头孢烷酸(7-ACA)与5-巯基-1,2,3,4-四氮唑-1-甲基磺酸双钠盐(SMT)在BF3作用下缩合,"一锅法"反应生成7-氨基-3-[甲磺酸基-1-H-四唑-5-基-巯甲基]-3-头孢烯4一羧酸(7-AMT)。7-AMT与D-(-)-甲酰基扁桃酸酰氯在pH 6.5～7.0下酰化,在盐酸作用下去甲酰基成头孢尼西酸,再与N,N-二苄基乙二胺二醋酸盐(DBED)结合生成头孢尼西胺盐(头孢尼西DBED)。胺盐经过强酸性阳离子树脂交换,成盐反应得头孢尼西钠。结果与结论:本工艺反应路线缩短,头孢尼西钠反应总收率提高至74.5%,操作简单,适合工业化生产。     

盐酸度洛西汀的合成

目的:合成盐酸度洛西汀.方法:以2-乙酰噻吩、盐酸二甲胺和多聚甲醛为起始原料,经Mannich反应、还原、拆分、成醚、成盐、两次重结晶等6步反应得到盐酸度洛西汀.结果:目标物经质谱、核磁共振氢谱及元素分析等确证其化学结构,总收率为7%.结论:本路线可简化实验操作,降低成本,适合工业化生产.     

Real-time endpoint monitoring and determination for a pharmaceutical salt formation process with in-line FT-IR spectroscopy

An application of Fourier transform infrared (FT-IR) spectroscopy equipped with an attenuated total reflectance (ATR) probe for in-line monitoring of a hydrochloride (HCl) salt formation process of 4-{1-methyl-2-piperidin-4-yl-4-[3-(trifluorometryl)phenyl]-1H-imidazol-5-yl}-N-[(1S)-1-phenylethyl]pyridine-2-amine (freebase), an active pharmaceutical ingredient as a P38 MAP kinase inhibitor, is described. The freebase forms both mono- and bis-HCl salts due to its structural features. The mono-HCl salt is the desired product but the bis-salt is an impurity. The key to maximizing the product yield and minimizing the impurity level is to monitor the salt-forming reaction and to terminate it at the correct HCl charge amount. The process analytical technology (PAT) provided real-time data for process control and overcame the limitations that had been previously encountered by other analytical instrumentations, such as high-performance liquid chromatography and titration. Two qualitative approaches for reaction endpoint determination were employed. In the first approach, changes in the concentration of the freebase and bis-salt were monitored via the first derivative concentration profiles. The flat point in the freebase profile and the rise in the bis-salt profile were used as a detection bracket for the endpoint of HCl charging. In the second approach, principal component analysis (PCA) was used to classify the status of the process based on a spectral library consisting of spectra collected around the endpoint. Results indicated that both methods provided adequate accuracy for endpoint control in a small window between 1.0 and 1.05 HCl to freebase mole ratio. Both methods were used to support a scaled up process. Three batches of MAP mono-HCl salt formation were successfully controlled and prepared.     

盐酸西布曲明的合成工艺改进

目的研究盐酸西布曲明适合工业化大生产的方法。方法以对氯氯苄为原料,经取代、环合、加成、还原、二甲基化及成盐等反应合成盐酸西布曲明,并对反应条件进行了改进和优化。结论工艺经改进和优化后,反应条件温和,操作简便,工艺稳定,总收率达到57.8%,大幅度的降低了生产成本,更加适合工业化生产。