米那普仑杂质 | 153275-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 米那普仑杂质
• 英文名称: 1-phenyl-3-aza-bicyclo[3.1.0]hexan-2-one
• 英文别名: 1-Phenyl-3-azabicyclo[3.1.0]hexan-2-one
• CAS: 153275-06-0
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: VQWWQAXEUWHNDU-UHFFFAOYSA-N

物化性质

• 熔点：
  85 - 88°C
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  米那普仑杂质 在 盐酸 、 水 作用下， 以66%的产率得到1-phenyl-2-(aminomethyl)cyclopropanecarylic acid hydrochloride
  参考文献：
  名称：

  金催化N-烯丙基乙酰胺的氧化环丙烷化反应合成3-氮杂双环[3.1.0]己-2-酮衍生物

  摘要：

  使用IMesAuCl / AgBF 4作为催化剂，吡啶N-氧化物作为溶剂，可以将具有各种官能团和不同取代方式的N-烯丙基炔酰胺以中等至高产率转化为3-氮杂双环[3.1.0]己-2-酮衍生物。氧化剂。提出了非卡宾介导的方法作为机理。

  DOI：

  10.1021/ol4007629
• 作为产物：
  描述：

  1-phenyl-3-(2-(trimethylsilyl)ethylsulfonyl)-3-aza-bicyclo[3.1.0]hexan-2-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以70%的产率得到米那普仑杂质
  参考文献：
  名称：

  金催化N-烯丙基乙酰胺的氧化环丙烷化反应合成3-氮杂双环[3.1.0]己-2-酮衍生物

  摘要：

  使用IMesAuCl / AgBF 4作为催化剂，吡啶N-氧化物作为溶剂，可以将具有各种官能团和不同取代方式的N-烯丙基炔酰胺以中等至高产率转化为3-氮杂双环[3.1.0]己-2-酮衍生物。氧化剂。提出了非卡宾介导的方法作为机理。

  DOI：

  10.1021/ol4007629

文献信息

• Production Method of Polycyclic Lactams
  申请人：Hirata Norihiko

  公开号：US20090118519A1

  公开（公告）日：2009-05-07

  A process for producing lactams of formula (1) below, including the step of reacting lactones of formula (2) below with imides of any of formulae (3a), (3b) and (3c) to thereby obtain corresponding carboxylic acids (step A); the step of esterifying the carboxylic acids into corresponding esters (step B); and the step of reacting the esters with amines to thereby obtain lactams of the formula (1) (step C). In the formulae (1)-(2) and (3a)-(3c), when R 3 and R 4 are simultaneously hydrogen atoms, R is a substituted methylene or optionally substituted polymethylene; when at least one of R 3 and R 4 is a substituent other than hydrogen atom, R is an optionally substituted methylene or polymethylene; each of R 3 , R 4 , R 5 and R 6 independently is a hydrogen atom, a halogen atom, cyano, etc.; each of A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , A 9 and A 10 independently is a hydrogen atom, a halogen atom, nitro, etc.; and M is a hydrogen atom or an alkali metal atom.

  以下为制备式（1）内的内酰胺的方法，包括将制备式（2）的内酯与制备式（3a）、（3b）或（3c）的亚酰胺反应，从而得到相应的羧酸（步骤A）；酯化羧酸以得到相应的酯（步骤B）；将酯与胺反应以得到制备式（1）的内酰胺（步骤C）。在制备式（1）-（2）和（3a）-（3c）中，当R3和R4同时为氢原子时，R为取代亚甲基或可选的取代聚亚甲基；当R3和R4中至少有一个是除氢原子以外的取代基时，R为可选的取代亚甲基或聚亚甲基；R3、R4、R5和R6中的每一个独立地是氢原子、卤素原子、氰基等；A1、A2、A3、A4、A5、A6、A7、A8、A9和A10中的每一个独立地是氢原子、卤素原子、硝基等；M为氢原子或碱金属原子。
• Novel Compounds
  申请人：Arista Luca

  公开号：US20080227837A1

  公开（公告）日：2008-09-18

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl and SF 5 ; or corresponds to a group R 5 ; R 2 is hydrogen or C 1-4 alkyl; R 3 is C 1-4 alkyl; R 4 is C 1-4 alkyl or C 1-6 cycloalkyl optionally substituted by 1 or 2 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1 -dioxido- 2 -isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2 -pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D 3 receptors, as antipsychotic agents, or to treat obsessive compulsive spectrum disorders or premature ejaculation.

  本发明涉及公式（I）的新化合物或其药学上可接受的盐：其中G选择自以下组：苯基，吡啶基，苯并噻唑基，吲哚基；p是从0到5的整数；R1独立地选择自以下组：卤素，羟基，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基和SF5；或对应于R5基团；R2是氢或C1-4烷基；R3是C1-4烷基；R4是C1-4烷基或C1-6环烷基，可选地被1或2个来自以下组的取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基；R5是从以下组中选择的基团：异恶唑基，-CH2-N-吡咯基，1,1-二氧化-2-异硫氰酸酰基，噻唑基，噻唑啉基，吡啶基，2-吡咯烷酰基，该基团可选地被1或2个取代基所取代，所述取代基选择自：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基；以及用于制备这些化合物的中间体，包含它们的制药组合物以及它们作为多巴胺D3受体调节剂、抗精神病药物或用于治疗强迫症谱系障碍或早泄的用途。
• Azabicyclo (3.1.0) Hexane Derivatives Useful as Modulators of Dopamine D3 Receptors
  申请人：Hamprecht Dieter

  公开号：US20080167357A1

  公开（公告）日：2008-07-10

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl and indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl and SF 5 ; or corresponds to a group R 5 ; each R 2 is independently hydrogen or C 1-4 alkyl; n is 2, 3, 4 or 5; R 3 is C 1-4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl and SF 5 ; R 5 is selected from a group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl and 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from a group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy and C 1-4 alkanoyl; and when R 1 corresponds to R 5 , p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D 3 receptors, e.g. to treat drug dependency, as antipsychotic agents, to treat obsessive compulsive spectrum disorders, premature ejaculation or cognition impairment.

  本发明涉及公式（I）的新化合物或其药学上可接受的盐： 其中， G选自以下一组：苯基，吡啶基，苯并噻唑基和吲唑基； p为0到5之间的整数； R1独立地选自以下一组：卤素，羟基，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基和SF5；或对应于R5基团； 每个R2独立地为氢或C1-4烷基； n为2、3、4或5； R3为C1-4烷基； R4为氢，或苯基，杂环基，5-或6-成员杂芳基或8-到11-成员的双环基中的任何一种，其中任何一种基团均可选择性地被1、2、3或4个来自以下一组的取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基和SF5； R5选自以下一组：异恶唑基，-CH2-N-吡咯基，1,1-二氧化-2-异噻唑烷基，噻吩基，噻唑基，吡啶基和2-吡咯烷基，这样的基团可以选择性地被来自以下一组的一个或两个取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基和C1-4酰基； 当R1对应于R5时，p为1； 用于其制备的中间体，包含它们的制药组合物以及它们在治疗中的用途，作为多巴胺D3受体调节剂，例如用于治疗药物依赖症、作为抗精神病剂、治疗强迫症谱系障碍、早泄或认知障碍。
• N-Tert-Butoxycarbonyl-2-Pyrrolidinones and Production Method Thereof
  申请人：Hirata Norihiko

  公开号：US20100280259A1

  公开（公告）日：2010-11-04

  N-tert-butoxycarbonyl-2-pyrrolidinones represented by the following formula (1). In the formula (1), R1, R2, R3, R4, R5 and R6 independently represent a hydrogen atom, a halogen atom, a cyano group, a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, which may have a substituent, a linear, branched or cyclic alkenyl group having 2 to 10 carbon atoms, which may have a substituent, or the like, R1 and R2 may be linked to form a >C═O group along with the carbon atom to which both are attached, R3 and R4 may be linked to form a >C═O group along with the carbon atom to which both are attached, R5 and R6 may be linked to form a >C═O group along with the carbon atom to which both are attached, or any two among R1, R2, R3, R4, R5 and R6 may be linked to form a polymethylene group having 1 to 4 carbon atoms which may have a substituent.

  以下公式（1）表示N-tert-丁氧羰基-2-吡咯酮。在公式（1）中，R1，R2，R3，R4，R5和R6独立地表示氢原子，卤素原子，氰基，具有1到10个碳原子的线性，支链或环状烷基，可以具有取代基，具有2到10个碳原子的线性，支链或环状烯基，可以具有取代基，或类似物，R1和R2可以连接形成>C═O基团，同时与它们附着的碳原子，R3和R4可以连接形成>C═O基团，同时与它们附着的碳原子，R5和R6可以连接形成>C═O基团，同时与它们附着的碳原子，或者R1，R2，R3，R4，R5和R6中的任意两个可以连接形成具有1到4个碳原子的聚亚甲基基团，可以具有取代基。
• Azabicyclo (3.1.0) Hexane Derivatives Useful As Modulators Of Dopamine D3 Receptors
  申请人：Arista Luca

  公开号：US20100152195A1

  公开（公告）日：2010-06-17

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl; or corresponds to a group R 5 ; R 2 is hydrogen or C 1-4 alkyl; R 3 is C 1-4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; and when R 1 is chlorine and p is 1, such R 1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R 1 corresponds to R 5 , p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D 3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

  本发明涉及公式（I）的新化合物或其药学上可接受的盐： 其中， G选自以下组：苯基，吡啶基，苯并噻唑基，吲唑基； p为0至5的整数； R1独立地选自以下组：卤素，羟基，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基；或对应于R5的基团； R2为氢或C1-4烷基； R3为C1-4烷基； R4为氢，苯基，杂环基，5-或6-成员杂芳基，或8-到11-成员双环基中的任何一种，其中任何一种基团均可选择地被1、2、3或4个取代基所取代，所述取代基选自以下组：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基； R5为以下组中选择的基团：异恶唑基，—CH2—N-吡咯基，1，1-二氧化-2-异噻唑烷基，噻唑基，噻唑基，吡啶基，2-吡咯烷酮基，所述基团可选择地被1或2个取代基所取代，所述取代基选自以下组：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基； 当R1为氯且p为1时，该R1不位于与分子其余部分的连接键的邻位；当R1对应于R5时，p为1； 本发明还涉及制备这些化合物的方法，用于这些方法的中间体，包含它们的制药组合物以及它们作为多巴胺D3受体调节剂的用途，例如用于治疗药物依赖或作为抗精神病药物。