trans N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carboxylic acid amide 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 N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carboxylic acid amide hydrochloride
• 英文别名: trans N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carbonic amide hydrochloride；trans-N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carbonic amide hydrochloride；N-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]morpholine-4-carboxamide;hydrochloride
• 化学式: C₂₃H₃₄Cl₂N₄O₂*(x)ClH
• 分子量: 505.9
• InChiKey: CVZCFHCDHXPIBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  48
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  trans N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carboxylic acid amide 在 盐酸 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 1.0h， 生成 trans N-{4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-cyclohexyl}-morpholine-4-carboxylic acid amide hydrochloride
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF PIPERAZINE COMPOUNDS AND HYDROCHLORIDE SALTS THEREOF
  [FR] PROCEDE DE PREPARATION DE COMPOSES DE PIPERAZINE ET SELS HYDROCHLORURES DE CEUX-CI

  摘要：

  公开号：

  WO2010070370A8

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 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。
• CARBAMOYL CYCLOHEXANE DERIVATIVES FOR TREATING AUTISM SPECTRUM DISORDER
  申请人：Richter Gedeon Nyrt.

  公开号：EP3952872A1

  公开（公告）日：2022-02-16
• US8569498B2
  申请人：——

  公开号：US8569498B2

  公开（公告）日：2013-10-29
• [EN] CARBAMOYL CYCLOHEXANE DERIVATIVES FOR TREATING AUTISM SPECTRUM DISORDER<br/>[FR] DÉRIVÉS DU CARBAMOYL CYCLOHEXANE POUR TRAITER LES TROUBLES DU SPECTRE AUTISTIQUE
  申请人：RICHTER GEDEON NYRT

  公开号：WO2020208564A1

  公开（公告）日：2020-10-15

  The present invention relates to trans-N-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-N',N'-dimethylurea (cariprazine), its salts, close analogs, derivatives, pharmaceutical compositions, metabolites and combinations for use in the treatment of symptoms of autism spectrum disorder in general, and preferably the object of the present invention is to treat one or more symptoms of autism. Furthermore, it was also found that cariprazine, its salts, close analogs, derivatives, pharmaceutical compositions, metabolites and combinations are suitable for treatment of conditions such as Asperger's syndrome, atypical autism (otherwise known as pervasive developmental disorder not otherwise specified; PDD-NOS), Rett syndrome, childhood disintegrative disorder, attention deficit hyperactivity disorder (ADHD) and sensory integration dysfunction.