合成利奈唑胺的工艺改进

以3,4-二氟硝基苯为原料,经亲核取代、催化氢化、氨基保护、环合反应、盐酸化脱Boc、乙酰化等6步反应合成了利奈唑胺,总收率62%,其结构经1H NMR,IR和MS确证。     

泰地唑胺的合成工艺改进

以4-溴-3-氟苯胺为原料,用氯甲酸苄酯保护氨基后,采用一锅两步法制得关键中间体--N-苄氧羰基-3-氟-4-［2-(2-甲基四唑-5-基)吡啶-5-基］苯胺（6）; 6在二异丙基氨基锂作用下与(R)-丁酸缩水甘油酯经环合反应合成了泰地唑胺,总收率53.2%,含量98.5%,其结构经¹H NMR和LC-MS确证。     

利奈唑胺注射液中主要降解产物的合成

以利奈唑胺为起始原料,利用LiOH选择性水解利奈唑胺的酯键和酰胺键,得利奈唑胺注射液中的部分水解产物N-[(2R)-3-[[3-氟-4-(4-吗啉基)苯基]氨基]-2-羟基丙基]-乙酰胺(2)和完全水解杂质(2S)-1-氨基-3-[[3-氟-4-(4-吗啉基)苯基]氨基]-2-丙醇(4),收率分别为78.3%和86.6%;然后将化合物4的末端氨基用叔丁氧羰基保护,经N,O-双乙酰化后用氨水/甲醇脱除O-乙酰基,再利用饱和氯化氢乙醚溶液脱除叔丁氧羰基保护基,得N-[(2S)-3-氨基-2-羟基丙基]-N-[3-氟-4-(4-吗啉基)苯基]-乙酰胺(3)盐酸盐,五步总收率62.3%.     

多齿鳌合配体双四唑胺合成方法的改进

用水热法合成并提纯双四唑胺,优化了传统合成方法并使实验步骤缩减,使产率和纯度有较大提高。     

阿立哌唑的合成方法研究进展

综述了近年来阿立哌唑的合成方法研究进展,并讨论了各种方法的优缺点.     

磷酸特地唑胺的合成新方法

以(5R)-3-(4-溴-3-氟苯基)-5-羟甲基噁唑烷-2-酮为起始原料,在[PdCl₂(dppf)]·CH₂Cl₂催化下与联硼酸频那醇酯反应得到硼化物,继而与5-溴-2-(2-甲基-2H-四唑-5-基)吡啶进行Suzuki反应得到特地唑胺,收率82.9%。 分别考察了催化体系对硼化反应和Suzuki反应的影响,确定了较佳的反应条件。 特地唑胺与二苄基N,N-二异丙基亚磷酰胺反应得到二苄基保护的磷酸特地唑胺,随后经Pd/C脱苄得到磷酸特地唑胺,总收率66.2%。     

美金刚胺衍生物的合成

以盐酸美金刚胺为原料,分别与对硝基苯甲酰氯,苄氧羰基缬氨酸经酰基化反应和催化加氢反应,合成了两个新型的美金刚胺衍生物——N-对氨基苯甲酰基美金刚胺和缬氨酰基美金刚胺,其结构经1H NMR和IR表征。     

阿立哌唑的合成

以2,3-二氯苯胺为原料,经3步亲核取代反应合成了阿立哌唑。3步反应的收率分别为83%,91%和90%;总收率68%。阿立哌唑的结构经1H NMR,IR和元素分析表征。     

盐酸帕唑帕尼的合成工艺改进

以2-乙基苯胺为原料,经硝化、环合和甲基化反应制得2,3-二甲基-N-(2-氯嘧啶-4-基)-N-甲基-2H-吲唑-6-胺(8);8与2-甲基-5-氨基苯磺酰胺经缩合和成盐反应合成了盐酸帕唑帕尼,总收率39.6%,其结构经1H NMR和MS确证。     

抗癫痫药舒噻嗪的合成工艺研究

以四氢呋喃为原料 ,经酯化、磺化、酰氯化、缩合、环化等步骤 ,合成了化学名为 4_(四氢_2H_1,2_噻嗪基_2 )苯磺酰胺_S_S_二氧化物的抗癫痫药舒噻嗪 (sulthiame) ,通过IR、1HNMR和元素分析对其结构进行了表征     

A Validated Stability-Indicating LC Method for Zonisamide

A simple, isocratic, rapid, and accurate reversed-phase high-performance liquid chromatographic method has been established for quantitative determination of zonisamide. The method is also applicable to determination of related substances in the bulk drug. Chromatographic separation was achieved on a 250 mm × 4.6 mm, 5-μm particle, C₁₈ column; the mobile phase was a 70:30 (v/v) mixture of 0.1% (v/v) aqueous triethylamine, adjusted to pH 2.5 with dilute orthophosphoric acid, and acetonitrile. Chromatographic resolution of zonisamide from its potential impurity, A, was found to be >2. The limits of detection and quantification of zonisamide and impurity A were 0.04 and 0.12 μg mL⁻¹, respectively, for 20 μL injection volume. Recovery of zonisamide ranged from 98.5 to 101.2% and recovery of impurity A from a sample of zonisamide ranged from 97.4 to 102.7%. The method was validated for linearity, accuracy, precision, and robustness.

     

A Validated Stability-Indicating LC Method for Zonisamide

A simple, isocratic, rapid, and accurate reversed-phase high-performance liquid chromatographic method has been established for quantitative determination of zonisamide. The method is also applicable to determination of related substances in the bulk drug. Chromatographic separation was achieved on a 250 mm × 4.6 mm, 5-μm particle, C₁₈ column; the mobile phase was a 70:30 (v/v) mixture of 0.1% (v/v) aqueous triethylamine, adjusted to pH 2.5 with dilute orthophosphoric acid, and acetonitrile. Chromatographic resolution of zonisamide from its potential impurity, A, was found to be >2. The limits of detection and quantification of zonisamide and impurity A were 0.04 and 0.12 μg mL^?1, respectively, for 20 μL injection volume. Recovery of zonisamide ranged from 98.5 to 101.2% and recovery of impurity A from a sample of zonisamide ranged from 97.4 to 102.7%. The method was validated for linearity, accuracy, precision, and robustness.     

Electroreduction of Zonisamide at Hanging Mercury Drop Electrode and Its Determination in Pharmaceutical Formulations and Spiked Human Serum Samples

A simple and rapid voltammetric method has been developed for the quantitative determination of zonisamide (ZNS) in pharmaceutical formulations and spiked human serum samples. Studies with differential pulse voltammetry (DPV) were carried out using a hanging mercury drop electrode (HMDE) in 0.1 M HCl solution. A well-defined reduction peak of ZNS was obtained at ?930 mV vs. saturated calomel electrode (SCE). The current-concentration plots are linear over the range from 0.13 to 17.05 μg ml^?1 in 0.1 M HCl. The statistical parameters and the recovery study data clearly indicate good reproducibility and accuracy of the method.     

High-Performance Liquid Chromatographic Assay of Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in Human Plasma using a Solid-Phase Extraction Technique

A selective and sensitive liquid chromatographic method was developed for the determination of zonisamide in small volumes of plasma. Zonisamide and the internal standard methyl 4-hydroxybenzoate were extracted from 0.2 mL of plasma with solid-phase extraction columns and eluted with methanol. Analysis of the extracts was performed on a Symmetry C₁₈ column with ultra-violet spectrophotometric detection. The calibration curve was linear over the concentration range of 0.05–5 g mL^–1 in plasma. Recoveries were reasonable for routine analyses; the limit of quantification was 0.05 g mL^–1 with a signal-to-noise ratio of 5. This method could be useful for the pharmacokinetic study of zonisamide in a limited volume of human plasma and for therapeutic drug monitoring.     

Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice

In this research, a UHPLC–MS/MS method was developed and validated for the determination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 µm particle size) column with mobile phase comprising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min, the column temperature was 30 °C and the injection volume was 3 µL. Desolvation temperature, desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS areas were determined by the image processing tool. The influence of hematocrit values (20–60%) on accuracy and precision was evaluated to determine the range within which method for DBSs is free from Hct or dependency is within acceptable limits. The validated method was applied to the determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was estimated by correlating its DPS and DBS levels.     

Synthesis of

A series of 1,1'-dicinnamoylferrocenes were converted to the corresponding [3]ferrocenophane diols (4a-e) in a stereoselective manner by using samarium diiodide to effect the intramolecular coupling reaction, aldol reaction, and reduction in one-pot operation. The major reaction pathway might be derived from a samarium chelated transition state (I(A)()) having the moieties of s-cis enone and (Z)-enolate. A solid-state structure of such [3]ferrocenophane diol product showed that the cyclopentadienyl groups were in an eclipsed orientation and slightly tilted.     

微波作用下1,5-苯并硫氮杂-α-溴代-β-内酰胺衍生物的合成

1,5-苯并硫氮杂     

N-酰基吡唑类化合物的制备及其在合成中的应用

N-酰基吡唑类化合物作为酰化试剂逐步引起了广泛关注,对其制备以及在醇解,氨解,格氏反应,瑞福尔马斯基反应等方面的用途做了探讨.     

发散法合成树枝状高分子聚酰胺-胺

采用发散法,以乙二胺为原料,通过与丙烯酸甲酯和乙二胺进行Mickeal加成和酰胺化缩合反应,合成了以乙二胺为核、支化代为1.0的树枝状高分子聚酰胺一胺,讨论了反应温度、反应时间和投料摩尔比等因素对反应的影响,同时讨论了该反应的特点。结果表明：适宜的反应温度为25℃,反应时间为24h,投料比为mol0.5代PAMAM：mol乙二胺＝1：24,在此条件下,产品的产率为99.9%,纯度在995以上。