摘要：【中文】本发明涉及一种如式I所示化合物环己烷衍生物N′‑[反式‑4‑[2‑[7‑(苯并[b]噻吩)‑7‑哌嗪基]乙基]环己基]‑N，N‑二甲基脲的马来酸盐及其晶型。该晶型引湿性低，稳定性好，便于长期存储和运输；体内实验还证明，其半衰期长，生物利用度高、个体差异性小。 【EN】The invention relates to a cyclohexane derivative N' - [ trans-4- [2- [7- (benzo [ b ]) as shown in a formula I]Thiophene) -7-piperazinyl]Ethyl radical]Cyclohexyl radical]-maleate salts of N, N-dimethylurea and crystalline forms thereof. The crystal form has low hygroscopicity, good stability and convenient long-term storage and transportation; in vivo experiments also prove that the compound has long half-life period, high bioavailability and small individual difference.

摘要：【中文】本发明涉及一种如式I所示化合物环己烷衍生物N′‑[反式‑4‑[2‑[7‑(苯并[b]噻吩)‑7‑哌嗪基]乙基]环己基]‑N，N‑二甲基脲的磷酸盐及其晶型。该磷酸盐经体内实验证明其生物利用度高、半衰期较长，是式I化合物的理想盐基。 【EN】The invention relates to a cyclohexane derivative N' - [ trans-4- [2- [7- (benzo [ b ]) as shown in a formula I]Thiophene) -7-piperazinyl]Ethyl radical]Cyclohexyl radical]-phosphates of N, N-dimethylurea and crystalline forms thereof. The phosphate is proved by in vivo experiments to have high bioavailability and longer half-life period, and is an ideal base of the compound shown in the formula I.

摘要：【中文】本发明涉及一种如式I所示化合物环己烷衍生物N′‑[反式‑4‑[2‑[7‑(苯并[b]噻吩)‑7‑哌嗪基]乙基]环己基]‑N，N‑二甲基脲的硫酸盐及其晶型。该硫酸盐的体内实验还证明其生物利用度高、体内起效快，是式I化合物的理想盐基。 【EN】The invention relates to a cyclohexane derivative N' - [ trans-4- [2- [7- (benzo [ b ]) as shown in a formula I]Thiophene) -7-piperazinyl]Ethyl radical]Cyclohexyl radical]-sulfates of N, N-dimethylurea and crystalline forms thereof. In vivo experiments of the sulfate also prove that the sulfate has high bioavailability and quick in vivo effect, and is an ideal salt base of the compound shown in the formula I.

摘要：【中文】本发明涉及一种如式I所示化合物环己烷衍生物N′‑[反式‑4‑[2‑[7‑(苯并[b]噻吩)‑7‑哌嗪基]乙基]环己基]‑N，N‑二甲基脲的盐酸盐及其晶型。该盐酸盐稳定性好、吸湿性低、体内研究还发现，相比游离碱以及其他盐类，该盐酸盐体内半衰期长，具有明显的临床应用优势 【EN】The invention relates to a cyclohexane derivative N' - [ trans-4- [2- [7- (benzo [ b ]) as shown in a formula I]Thiophene) -7-piperazinyl]Ethyl radical]Cyclohexyl radical]Hydrochloride of (E) -N, N-dimethyl urea and crystal forms thereof. The hydrochloride has good stability and low hygroscopicity, and in vivo research also finds that compared with free alkali and other salts, the hydrochloride has long in vivo half-life period and has obvious clinical application advantages

摘要：【中文】本发明公开了一种如式V所示的匹莫范色林杂质及其制备方法，本发明的制备方法能够制得高纯度的该匹莫范色林杂质V，可用于杂质的定性和定量检测，利于匹莫范色林的质量控制和用药安全性 【EN】The invention discloses pimavanserin impurity shown as a formula V and a preparation method thereof, and the preparation method can be used for preparing the high-purity pimavanserin impurity V, can be used for qualitative and quantitative detection of impurities, and is beneficial to quality control and medication safety of pimavanserin

摘要：【中文】本发明公开了一种匹莫范色林及其中间体的制备方法，该中间体的制备方法包括下述步骤：在碱存在下，将化合物M在有机溶剂中，与化合物SM和二氧化碳反应，即得化合物A；其中，R为C₁‑C₄的烷基、苄基或者取代的苄基，X为Cl、Br或I。本发明的制备方法操作简单，反应条件温和，收率较高，并且杂质含量低，易于纯化，能显著降低生产成本，易于工业化生产。 【EN】The invention discloses a preparation method of pimavanserin and an intermediate thereof, and the preparation method of the intermediate comprises the following steps: in the presence of alkali, reacting the compound M with a compound SM and carbon dioxide in an organic solvent to obtain a compound A; wherein R is C₁‑C₄And X is Cl, Br or I. The preparation method has the advantages of simple operation, mild reaction conditions, higher yield, low impurity content, easy purification and obvious effectThe production cost is reduced obviously, and the industrial production is easy to realize.

摘要：【中文】本发明涉及一种从布瓦西坦原料药中基因毒性警示中间体杂质4‑卤代‑R‑3‑丙基丁酸酯的方法，包括以下步骤：1)将布瓦西坦原料药溶解在极性溶剂中；2)在步骤1)的溶液中加入与极性溶剂不相溶的非极性溶剂进行萃取，使得极性溶剂液相与非极性溶剂液相形成分层，并对两个液相进行分离；3)将步骤2)中得到的极性溶剂层进行减压浓缩干燥，使用惰性溶剂进行重结晶，得到布瓦西坦晶体。本发明得到的布瓦西坦纯度高，基因毒性警示杂质含量小于7.5ppm，符合FDA规定，满足高端市场需求。 【EN】The invention relates to a method for preparing a genotoxicity warning intermediate impurity 4-halogenated-R-3-propyl butyrate from a bulk drug of Buvalracetam, which comprises the following steps: 1) dissolving a bulk drug of the brivaracetam in a polar solvent; 2) adding a non-polar solvent which is not soluble with the polar solvent into the solution obtained in the step 1) for extraction, so that a polar solvent liquid phase and a non-polar solvent liquid phase are layered, and separating the two liquid phases; 3) concentrating and drying the polar solvent layer obtained in the step 2) under reduced pressure, and recrystallizing by using an inert solvent to obtain the brivaracetam crystal. The prepared brivaracetam has high purity, the genotoxicity warning impurity content is less than 7.5ppm, the requirements of FDA are met, and the high-end market requirements are met.

摘要：【中文】本发明涉及一种如式I所示化合物环己烷衍生物N'‑[反式‑4‑[2‑[7‑(苯并[b]噻吩)‑4基‑1‑哌嗪]乙基]环己基]‑N,N‑二甲基脲的马来酸盐晶型的制备方法，该晶型为无水晶型，制备方法在水活度小于等于0.6溶剂条件下生成。 【EN】The invention relates to a cyclohexane derivative N' - [ trans-4- [2- [7- (benzo [ b ]) as shown in a formula I]Thiophen) -4 yl-1-piperazines]Ethyl radical]Cyclohexyl radical]The preparation method of the maleate crystal form of the (E) -N, N-dimethylurea is an anhydrous crystal form and is generated under the condition that the water activity is less than or equal to 0.6 solvent.

摘要：【中文】本发明提供了一种新的布瓦西坦中间体及其制备方法，并且将该中间体应用到制备布瓦西坦中。该方法操作简单、环境友好、收率高，且光学纯度好。 【EN】The invention provides a novel intermediate of brivaracetam and a preparation method thereof, and the intermediate is applied to preparation of brivaracetam. The method has the advantages of simple operation, environmental protection, high yield and good optical purity.

摘要：【中文】本发明公开了7‑哌嗪基苯并噻吩或其盐的制备方法，其包括：(1)化合物3与化合物4进行取代关环反应，得到化合物5；(2)化合物5进行水解脱羧，得到化合物6；(3)对化合物6进行硝基还原反应，得到化合物7；(4)化合物7与化合物8‑1的盐进行反应，即得。本发明的制备方法可以采用廉价的水杨醛作为起始物料，经多步反应后制备得到7‑哌嗪基苯并噻吩或其盐，该制备方法的合成路线中不使用昂贵的均相钯催化剂，生产成本低，操作简便，反应条件温和，且总反应收率较高。 【EN】The invention discloses a preparation method of 7-piperazinyl benzothiophene or a salt thereof, which comprises the following steps: (1) carrying out substitution ring closing reaction on the compound 3 and the compound 4 to obtain a compound 5; (2) hydrolyzing and decarboxylating the compound 5 to obtain a compound 6; (3) carrying out nitro reduction reaction on the compound 6 to obtain a compound 7; (4) and (3) reacting the compound 7 with a salt of the compound 8-1 to obtain the compound. The preparation method can adopt cheap salicylaldehyde as a starting material, and 7-piperazinyl benzothiophene or a salt thereof is prepared through multi-step reaction.