trans-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexanamine

• 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-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexanamine
• 英文别名: trans-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexylamine；trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-cyclohexyl-amine；trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexan-1-amine；4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexan-1-amine
• 化学式: C₁₈H₂₇Cl₂N₃
• 分子量: 356.338
• InChiKey: OSFYUOBMIMRRQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexanamine 以68的产率得到
  参考文献：
  名称：

  [EN] 1,4-CYCLOHEXYLAMINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
  [FR] DÉRIVÉS DE 1,4-CYCLOHEXYLAMINE ET LEURS PROCÉDÉS DE PRÉPARATION

  摘要：

  本发明涉及一种合成Cariprazine的方法，Cariprazine是一种抗精神病化合物，可用于治疗与精神分裂症相关的阳性和阴性症状，其结构式如下：（A）本发明还涉及合成中间体的方法，这些中间体可用于制备Cariprazine。

  公开号：

  WO2015056164A1
• 作为产物：
  描述：

  1-(2,3-二氯苯基)哌嗪 在 十二羰基三钌 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 trans-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexanamine
  参考文献：
  名称：

  [EN] 1,4-CYCLOHEXYLAMINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
  [FR] DÉRIVÉS DE 1,4-CYCLOHEXYLAMINE ET LEURS PROCÉDÉS DE PRÉPARATION

  摘要：

  本发明涉及一种用于合成卡瑞普利汀的方法，该化合物是一种抗精神病药物，可用于治疗与精神分裂症相关的阳性和阴性症状，其结构式如下：（A）。本发明还涉及合成有用于制备卡瑞普利汀的中间体的方法。

  公开号：

  WO2015056164A1

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。
• A New and Practical Synthesis of Cariprazine through the Facile Construction of 2-[trans-4-(3,3-Dimethylureido)cyclohexyl]acetic Acid
  作者：Lei Fu、Jianqi Li、Xiaowen Chen、Feng Ni、Yu Liu

  DOI：10.1055/s-0035-1561865

  日期：——

  confirmed by X-ray crystallographic analysis. A new, practical, and improved synthetic route to cariprazine is described. The key step is the facile preparation of 2-[4-(3,3-dimethylureido)cyclohexyl]acetic acid in the trans configuration through direct recrystallization. The entire synthetic procedure was accomplished under mild conditions while avoiding tedious purification processes. The trans configuration

  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。
• [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。
• [EN] (THIO) CARBAMOYL-CYCLOHEXANE DERIVATIVES AS D3/D2 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE (THIO) CARBAMOYL-CYCLOHEXANE UTILISES EN TANT QU'ANTAGONISTES DES RECEPTEURS D3/D2
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2005012266A1

  公开（公告）日：2005-02-10

  The present invention relates to new D3 and D2 dopamine receptor subtype preferring ligands of formula (I): wherein R1 and R2 represent independently a substituent selected from hydrogen, alkyl, aryl, cycloalkyl, aroyl, or R1 and R2 may form a heterocyclic ring with the adjacent nitrogen atom; X represents an oxygen or sulphur atom; n is an integer of from 1 to 2, and/or geometric isomers and/or stereoisomers and/or diastereomers and/or salts and/or hydrates and/or solvates thereof, to the processes for producing the same, to pharmaceutical compositions containing the same and to their use in therapy and/or prevention of a condition which requires modulation of dopamine receptors.

  本发明涉及新的D3和D2多巴胺受体亚型偏好配体，其化学式为（I）：其中R1和R2分别代表氢，烷基，芳基，环烷基，芳香酰基的取代基，或者R1和R2可以与相邻的氮原子形成杂环；X代表氧或硫原子；n为1至2的整数，以及它们的几何异构体和/或立体异构体和/或对映异构体和/或盐和/或水合物和/或溶剂化物，以及制备它们的方法，包含它们的制药组合物以及在需要调节多巴胺受体的情况下用于治疗和/或预防的用途。