trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl urea hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl urea hydrochloride
• 英文别名: trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine；trans 4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride；[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-(dimethylcarbamoyl)azanium;chloride
• 化学式: C₂₁H₃₂Cl₂N₄O*(x)ClH
• 分子量: 463.9
• InChiKey: GPPJWWMREQHLQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.76
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  cariprazine 在 盐酸 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 以91%的产率得到trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl urea hydrochloride
  参考文献：
  名称：

  通过2- [反式-4-（3,3-二甲基脲基）环己基]乙酸的轻松构建，新合成实用的卡比拉嗪

  摘要：

  摘要 描述了一种新的，实用的和改进的合成卡哌嗪的合成途径。关键步骤是通过直接重结晶轻松制备反式构型的2- [4-（3,3-二甲基脲基）环己基]乙酸。整个合成过程在温和的条件下完成，同时避免了繁琐的纯化过程。通过X射线晶体学分析证实了卡哌嗪的反式构型。 描述了一种新的，实用的和改进的合成卡哌嗪的合成途径。关键步骤是通过直接重结晶轻松制备反式构型的2- [4-（3,3-二甲基脲基）环己基]乙酸。整个合成过程在温和的条件下完成，同时避免了繁琐的纯化过程。通过X射线晶体学分析证实了卡哌嗪的反式构型。

  DOI：

  10.1055/s-0035-1561865

文献信息

• PROCESS FOR THE PREPARATION OF PIPERAZINE COMPOUNDS AND HYDROCHLORIDE SALTS THEREOF
  申请人：Czibula Laszlo

  公开号：US20110275804A1

  公开（公告）日：2011-11-10

  The invention relates to a new process for the preparation of compounds of general formula (I) wherein R 1 and R 2 represent independently hydrogen or C 1-6 alkyl with straight or branched chain optionally substituted with aryl group, or C 2-7 alkenyl containing 1-3 double bonds, or monocyclic, bicyclic or tricyclic aryl optionally substituted with one or more C1-6 alkoxy, trifluoro-C 1-6 alkoxy, C 1-6 -alkoxycarbonil, C 1-6 alkanoyl, aryl, C 1-6 alkylthio, halogen or cyano, or optionally substituted monocyclic, bicyclic or tricyclic C 3-14 cycloalkyl group, R 1 and R 2 together with the adjacent nitrogen form a saturated or unsaturated optionally substituted monocyclic or bicyclic heterocyclic ring which may contain further heteroatoms selected from oxygen, nitrogen, or sulphur atoms and hydrochloric acid alts and/or hydrates and/or solvates thereof, by dissolving or suspending trans 4-2-[4-(2,3-dichlorophenyl)-piperazine-1-il]-ethyl}-cyclohexylamine of formula (III) or a salt or a hydrate or a solvate thereof in an inert solvent in the presence a base then adding a carbonic acid derivative of general formula (VI) wherein R is alkyl with C 1-6 straight or branched chain or C 1-2 fully halogenated alkyl, Z is —O—R or —X, wherein R is as described above, X is halogen, and reacting the compound of general formula (IV) obtained wherein R is as described above, in situ or, optionally in isolated state with an amine of general formula (V) wherein R 1 and R 2 are as described above to obtain the compound of general formula (I) and then optionally forming the hydrochloride salts and/or hydrates and/or solvates thereof.

  该发明涉及一种制备通式（I）化合物的新工艺，其中R1和R2分别表示氢或C1-6烷基，可以是直链或支链，也可以用芳基取代，或者是含有1-3个双键的C2-7烯基，或者是单环、双环或三环芳基，可以用一个或多个C1-6烷氧基、三氟甲氧基、C1-6-烷氧羰基、C1-6烷酰基、芳基、C1-6烷基硫基、卤素或氰基取代，或者是可选择取代的单环、双环或三环C3-14环烷基，R1和R2连同相邻的氮形成饱和或不饱和、可选择取代的单环或双环杂环，可以含有进一步选择的氧、氮或硫原子的杂原子，以及其盐和/或水合物和/或溶剂化合物，通过在惰性溶剂中溶解或悬浮式地将通式（III）的反式4-2-[4-(2,3-二氯苯基)-哌嗪-1-基]-乙基}-环己胺或其盐或水合物或溶剂化合物，在碱存在下加入通式（VI）的碳酸衍生物，其中R是具有C1-6直链或支链的烷基或C1-2全氟化烷基，Z是-O-R或-X，其中R如上所述，X是卤素，然后与通式（V）的胺反应，其中R1和R2如上所述，以获得通式（I）的化合物，然后可选择形成其盐和/或水合物和/或溶剂化合物。
• [EN] NOVEL PROCESSES FOR THE PREPARATION OF TRANS-N-{4-[2-[4-(2,3-DICHLOROPHENYL)PIPERAZINE-1-YL]ETHYL] CYCLOHEXYL}-N',N'-DIMETHYLUREA HYDROCHLORIDE AND POLYMORPHS THEREOF<br/>[FR] NOUVEAUX PROCÉDÉS POUR LA PRÉPARATION DE CHLORHYDRATE DE TRANS-N-{4-[2-[4-(2,3-DICHLOROPHÉNYL)PIPÉRAZINE-1-YL]ÉTHYL] CYCLOHEXYL}-N',N'-DIMÉTHYL URÉE ET POLYMORPHES DE CELUI-CI
  申请人：MSN LABORATORIES PRIVATE LTD R&D CENTER

  公开号：WO2019016828A1

  公开（公告）日：2019-01-24

  The present invention relates to novel processes for the preparation of trans- N-4-[2- [4-(2,3-dichloro phenyl) piperazine-1-yl] ethyl] cyclohexyl} -N',N'-dimethylurea hydrochloride represented by the following structural formula-1a and polymorphs thereof. (I) The present invention also relates to novel intermediate compounds which are useful for the preparation of compound of formula-1a.

  本发明涉及一种用于制备trans-N-4-[2-[4-(2,3-二氯苯基)哌嗪-1-基]乙基]环己基}-N'，N'-二甲基脲盐酸盐的新工艺，其结构式如下-1a及其多晶形态。本发明还涉及一种有用于制备式-1a化合物的新中间体化合物。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF PIPERAZINE COMPOUNDS AND HYDROCHLORIDE SALTS THEREOF<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE COMPOSÉS DE PIPÉRAZINE ET DE SELS CHLORHYDRATES DE CEUX-CI
  申请人：RICHTER GEDEON NYRT

  公开号：WO2011073705A1

  公开（公告）日：2011-06-23

  The invention relates to a new process for the preparation of compounds of general formula (I) wherein R1 and R2 represent independently hydrogen or C1-6 alkyl with straight or branched chain optionally substituted with aryl group; or C2-7 alkenyl containing 1-3 double bonds; or monocyclic, bicyclic or tricyclic aryl optionally substituted with one or more C1-6 alkoxy, trifiuoro-C1-6 alkoxy, C1-6-alkoxycarbonil, C1-6alkanoyl, aryl, C1-6 alkylthio, halogen or cyano; or optionally substituted monocyclic, bicyclic or tricyclic C3-14 cycloalkyl group; R1 and R2 together with the adjacent nitrogen form a saturated or unsaturated optionally substituted monocyclic or bicyclic heterocyclic ring which may contain further heteroatoms selected from oxygen, nitrogen, or sulphur atoms and hydrochloric acid salts and/or hydrates and/or solvates thereof, by dissolving or suspending trans 4-2-[4-(2,3-dichlorophenyl)-piperazine-1-il]-ethyl}-cyclohexylamine of formula (III) or a salt or a hydrate or a solvate thereof in an inert solvent in the presence of a base then adding a carbonic acid derivative of general formula (VI) wherein R is alkyl with C1-6 straight or branched chain, partially or fully halogenated C1-2 alkyl or phenyl, Z is -O-R or -X, wherein R is as described above, X is halogen, and reacting the compound of general formula (IV) obtained wherein R is as described above, in situ or, optionally in isolated state with an amine of general formula (V) wherein R1 and R2 are as described above to obtain the compound of general formula (I) and then optionally forming the hydrochloride salts and/or hydrates and/or solvates thereof.

  本发明涉及一种新的制备通式（I）化合物的方法，其中R1和R2分别表示氢或C1-6直链或支链烷基，可选择地取代芳基；或含有1-3个双键的C2-7烯基；或单环、双环或三环芳基，可选择地取代一个或多个C1-6烷氧基、三氟甲基-C1-6烷氧基、C1-6-烷氧羰基、C1-6-烷酰基、芳基、C1-6烷硫基、卤素或氰基；或可选择地取代的单环、双环或三环C3-14环烷基；R1和R2与相邻的氮一起形成饱和或不饱和的、可选择地取代的单环或双环杂环环，该环可能包含进一步从氧、氮或硫原子中选择的杂原子以及其氯化氢盐和/或水合物和/或溶剂化合物，通过在惰性溶剂中溶解或悬浮通式（III）的反式4-2-[4-(2,3-二氯苯基)-哌嗪-1-基]-乙基}-环己基胺，或其盐或水合物或溶剂化合物，在碱存在下添加通式（VI）的碳酸衍生物，其中R为C1-6直链或支链烷基、部分或完全卤代的C1-2烷基或苯基，Z为-O-R或-X，其中R如上所述，X为卤素，并将所得的通式（IV）化合物在原位或可选地在分离状态下与通式（V）的胺反应，其中R1和R2如上所述，以获得通式（I）的化合物，然后可选择地形成其氯化氢盐和/或水合物和/或溶剂化合物。
• NOVEL SALTS OF PIPERAZINE COMPOUNDS AS D3/D2 ANTAGONISTS
  申请人：Czibula Laszlo

  公开号：US20090023750A1

  公开（公告）日：2009-01-22

  The present invention relates to novel monohydrochloride, dihydrochloride, monohydrobromide, maleate and methanesulphonate salts of trans 4-2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine and/or their hydrates and/or solvates. Moreover, the invention relates to the process for preparing the salts and their hydrates and/or solvates, to their use in the treatment and/or prevention of conditions which require modulation of dopamine receptor and to pharmaceutical compositions containing them.

  本发明涉及转4-2-[4-(2,3-二氯苯基)-哌嗪-1-基]-乙基}-N,N-二甲基氨基甲酰基环己胺的新单盐酸盐、双盐酸盐、单溴化盐、马来酸盐和甲磺酸盐及其水合物和/或溶剂化合物。此外，本发明涉及制备这些盐及其水合物和/或溶剂化合物的方法，以及它们在需要调节多巴胺受体的治疗和/或预防条件中的使用，以及包含它们的制药组合物。
• NOVEL POLYMORPS OF CARIPRAZINE HYDROCHLORIDE AND PREPARATION METHOD THEREOF AND USE OF SAME
  申请人：SHANGHAI BEGREAT PHARMATECH

  公开号：US20200231552A1

  公开（公告）日：2020-07-23

  The present disclosure discloses crystal forms A, B, and C of trans-N-4-[2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl]-cyclohexyl}-N′,N′-dimethylurea hydrochloride, a preparation method, and a medicinal use thereof. Compared to the existing crystalline forms, the new crystalline forms have clear advantages with respect to solubility, stability, and the preparation process.

  本公开披露了trans-N-4-[2-[4-(2,3-二氯苯基)-哌嗪-1-基]-乙基]-环己基}-N′,N′-二甲基脲盐酸盐的晶型A、B和C，其制备方法以及药物用途。与现有的晶型相比，新的晶型在溶解度、稳定性和制备过程方面具有明显的优势。