2-chloromethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester | 762288-01-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-chloromethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-(chloromethyl)-1-methylindole-3-carboxylate
• CAS: 762288-01-7
• 化学式: C₁₃H₁₄ClNO₂
• 分子量: 251.713
• InChiKey: XNBGDFYWMHJSEY-UHFFFAOYSA-N

物化性质

• 沸点：
  413.2±35.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloromethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester 在 2,6-二甲基吡啶 、 三甲基铝 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]-4-methyl-3H-pyrrolo[3,4-b]indol-1-one
  参考文献：
  名称：

  5-HT2C antagonists based on fused heterotricyclic templates: Design, synthesis and biological evaluation

  摘要：

  Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.034
• 作为产物：
  描述：

  ethyl 1,2-dimethylindole-3-carboxylate 在 N-氯代丁二酰亚胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 5.0h， 以94%的产率得到2-chloromethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] COMPOUNDS HAVING ACTIVITY AT 5HT2C RECEPTOR AND USES THEREOF
  [FR] COMPOSES AYANT UNE ACTIVITE AU NIVEAU DU RECEPTEUR 5HT2C ET LEURS UTILISATIONS

  摘要：

  公开了具有式（I）的化合物及其药学上可接受的盐：其中Q是苯或含有至少一个氮原子的6元杂芳基团；A是-(CH2-CH2)-，-(CH=CH)-，-(CH2)3-，-C(CH3)2-，-(CH=CH-CH2)-，或一个-(CHR3)-基团，其中R3是氢，卤素，羟基，氰基，硝基，C1-6烷基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基或C1-6烷基硫基；B是O，S或NR11，其中R11是氢，C1-6烷基，可选择地被C1-6烷氧基取代，或是C1-6烷酰基，可选择地被C1-6烷氧基取代；R1是卤素，氰基，C1-6烷基，C3-7环烷基，C3-7环烷氧基，C1-6烷氧基，C1-6烷基硫基，羟基，氨基，单或双C1-6烷基氨基，N-连接的4到7成员杂环基团，硝基，卤代C1-6烷基，卤代C1-6烷氧基，芳基，芳基C1-6烷基，芳基C1-6烷氧基，芳基C1-6烷硫基，COR4（其中R4是氨基，单或双C1-6烷基氨基或N-连接的4到7成员杂环基团），COOR5或COR6（其中R5和R6独立地是氢或C1-6烷基）；p是0，1，2或3；R2是氢，卤素，羟基，氰基，硝基，C1-6烷基，C1-6烷酰基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基，C1-6烷基硫基，氨基，单或双C1-6烷基氨基或N-连接的4到7成员杂环基团；X是氧，硫，-CH2-或NR8，其中R8是氢或C1-6烷基；Y是单键，-CH2-，-(CH2)2-或-CH=CH-；Z是一个可选择地取代的N-连接杂环基团或含有至少一个氮的C-连接的4到7成员杂环基团，或Z是-NR9R10，其中R9和R10独立地是氢或C1-6烷基。还公开了其制备方法及在治疗中的用途，例如在抑郁症和焦虑症的治疗中。

  公开号：

  WO2004081010A1

文献信息

• [EN] COMPOUNDS HAVING ACTIVITY AT 5HT2C RECEPTOR AND USES THEREOF<br/>[FR] COMPOSES AYANT UNE ACTIVITE AU NIVEAU DU RECEPTEUR 5HT2C ET LEURS UTILISATIONS
  申请人：GLAXO GROUP LTD

  公开号：WO2004081010A1

  公开（公告）日：2004-09-23

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein Q is phenyl or a 6-membered heteroaromatic group containing at least one nitrogen atom; A is -(CH2-CH2)-, -(CH=CH)-, -(CH2)3-, -C(CH3)2-, -(CH=CH-CH2)-, or a group -(CHR3)- wherein R3 is hydrogen, halogen, hydroxy, cyano, nitro, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkyloxy, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy or C1-6alkylthio; B is O, S or NR11, wherein R11 is hydrogen, C1-6alkyl optionally substituted by C1-6alkoxy, or is C1-6alkanoyl optionally substituted by C1-6alkoxy; R1 is halogen, cyano, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkyloxy, C1-6alkoxy, C1-6alkylthio, hydroxy, amino, mono- or di-C1- 6alkylamino, an N-linked 4 to 7 membered heterocyclic group, nitro, haloC1-6alkyl, haloC1-6alkoxy, aryl, arylC1-6alkyl, arylC1-6alkyloxy, arylC1-6alkylthio, COR4 (wherein R4 is amino, mono- or di-C1-6alkylamino or an N-linked 4 to 7 membered heterocyclic group), COOR5 or COR6 (wherein R5 and R6 are independently hydrogen or C1-6alkyl); p is 0, 1 or 2 or 3; R2 is hydrogen, halogen, hydroxy, cyano, nitro, C1-6alkyl, C1-6alkanoyl, C3-7cycloalkyl, C3-7cycloalkyloxy, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio, amino, mono- or di-C1-6alkylamino or an N-linked 4 to 7 membered heterocyclic group; X is oxygen, sulfur, -CH2- or NR8 wherein R8 is hydrogen or C1-6alkyl; Y is a single bond, -CH2-, -(CH2)2- or -CH=CH-; and Z is an optionally substituted N-linked heterocyclic group or a C-linked 4 to 7 membered heterocyclic group containing at least one nitrogen, or Z is -NR9R10 where R9 and R10 are independently hydrogen or C1-6alkyl. Method of preparation and uses thereof in therapy, such as for example in treatment of depression and anxiety, are also disclosed.

  公开了具有式（I）的化合物及其药学上可接受的盐：其中Q是苯或含有至少一个氮原子的6元杂芳基团；A是-(CH2-CH2)-，-(CH=CH)-，-(CH2)3-，-C(CH3)2-，-(CH=CH-CH2)-，或一个-(CHR3)-基团，其中R3是氢，卤素，羟基，氰基，硝基，C1-6烷基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基或C1-6烷基硫基；B是O，S或NR11，其中R11是氢，C1-6烷基，可选择地被C1-6烷氧基取代，或是C1-6烷酰基，可选择地被C1-6烷氧基取代；R1是卤素，氰基，C1-6烷基，C3-7环烷基，C3-7环烷氧基，C1-6烷氧基，C1-6烷基硫基，羟基，氨基，单或双C1-6烷基氨基，N-连接的4到7成员杂环基团，硝基，卤代C1-6烷基，卤代C1-6烷氧基，芳基，芳基C1-6烷基，芳基C1-6烷氧基，芳基C1-6烷硫基，COR4（其中R4是氨基，单或双C1-6烷基氨基或N-连接的4到7成员杂环基团），COOR5或COR6（其中R5和R6独立地是氢或C1-6烷基）；p是0，1，2或3；R2是氢，卤素，羟基，氰基，硝基，C1-6烷基，C1-6烷酰基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基，C1-6烷基硫基，氨基，单或双C1-6烷基氨基或N-连接的4到7成员杂环基团；X是氧，硫，-CH2-或NR8，其中R8是氢或C1-6烷基；Y是单键，-CH2-，-(CH2)2-或-CH=CH-；Z是一个可选择地取代的N-连接杂环基团或含有至少一个氮的C-连接的4到7成员杂环基团，或Z是-NR9R10，其中R9和R10独立地是氢或C1-6烷基。还公开了其制备方法及在治疗中的用途，例如在抑郁症和焦虑症的治疗中。
• Compounds having activity at 5ht2c receptor and uses thereof
  申请人：Hamprecht Dieter

  公开号：US20060281786A1

  公开（公告）日：2006-12-14

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein Q is phenyl or a 6-membered heteroaromatic group containing at least one nitrogen atom; A is —(CH 2 —CH 2 )—, —(CH═CH)—, —(CH 2 ) 3 —, —C(CH 3 ) 2 —, —(CH═CH—CH 2 )—, or a group —(CHR 3 )— wherein R 3 is hydrogen, halogen, hydroxy, cyano, nitro, C 16 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, haloC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy or C 1-6 alkylthio; B is O, S or NR 11 , wherein R 11 is hydrogen, C 1-6 alkyl optionally substituted by C 1-6 alkoxy, or is C 1-6 alkanoyl optionally substituted by C 1-6 alkoxy; R 1 is halogen, cyano, C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, C 1-6 alkoxy, C 1 - 6 alkylthio, hydroxy, amino, mono- or di-C 1-6 alkylamino, an N-linked 4 to 7 membered heterocyclic group, nitro, haloC 1 6 alkyl, haloC 1-6 alkoxy, aryl, arylC 1-6 alkyl, arylC 1-6 alkyloxy, arylC 1-6 alkylthio, COR 4 (wherein R 4 is amino, mono- or di-C 1-6 alkylamino or an N-linked 4 to 7 membered heterocyclic group), COOR 5 or COR 6 (wherein R 5 and R 6 are independently hydrogen or C 1-6 alkyl); p is 0, 1 or 2 or 3; R 2 is hydrogen, halogen, hydroxy, cyano, nitro, C 1-6 alkyl, C 1-6 alkanoyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, haloC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, C 1-6 alkylthio, amino, mono- or di-C 1-6 alkylamino or an N-linked 4 to 7 membered heterocyclic group; X is oxygen, sulfur, —CH 2 — or NR 8 wherein R 8 is hydrogen or C 1-6 alkyl; Y is a single bond, —CH 2 —, —(CH 2 ) 2 13 or —CH═CH—; and Z is an optionally substituted N-linked heterocyclic group or a C-linked 4 to 7 membered heterocyclic group containing at least one nitrogen, or Z is —NR 9 R 10 where R 9 and R 10 are independently hydrogen or C 1-6 alkyl. Method of preparation and uses thereof in therapy, such as for example in treatment of depression and anxiety, are also disclosed.

  公开了化合物式（I）及其药学上可接受的盐：其中Q是苯基或含有至少一个氮原子的6元杂环芳基基团；A是—（CH2—CH2）—，—（CH═CH）—，—（CH2）3—，—C（CH3）2—，—（CH═CH—CH2）—或—（CHR3）—基团，其中R3是氢，卤素，羟基，氰基，硝基，C16烷基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基或C1-6烷基硫基；B是O，S或NR11，其中R11是氢，C1-6烷基（可选地被C1-6烷氧基取代），或者是C1-6烷酰基（可选地被C1-6烷氧基取代）；R1是卤素，氰基，C1-6烷基，C3-7环烷基，C3-7环烷氧基，C1-6烷氧基，C1-6烷基硫基，羟基，氨基，单或双C1-6烷基氨基，N-连接的4至7元杂环基团，硝基，卤代C1-6烷基，卤代C1-6烷氧基，芳基，芳基C1-6烷基，芳基C1-6烷氧基，芳基C1-6烷基硫基，COR4（其中R4是氨基，单或双C1-6烷基氨基或N-连接的4至7元杂环基团），COOR5或COR6（其中R5和R6分别是氢或C1-6烷基）；p是0，1，2或3；R2是氢，卤素，羟基，氰基，硝基，C1-6烷基，C1-6烷酰基，C3-7环烷基，C3-7环烷氧基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基，C1-6烷基硫基，氨基，单或双C1-6烷基氨基或N-连接的4至7元杂环基团；X是氧，硫，—CH2—或NR8，其中R8是氢或C1-6烷基；Y是单键，—CH2—，—（CH2）2—或—CH═CH—；Z是可选取代的N-连接杂环基团或含有至少一个氮原子的C-连接4至7元杂环基团，或Z是—NR9R10，其中R9和R10分别是氢或C1-6烷基。公开了制备方法及其在治疗中的用途，例如治疗抑郁症和焦虑症。
• COMPOUNDS HAVING ACTIVITY AT 5HT2C RECEPTOR AND USES THEREOF
  申请人：GLAXO GROUP LIMITED

  公开号：EP1603914A1

  公开（公告）日：2005-12-14
• 5-HT2C antagonists based on fused heterotricyclic templates: Design, synthesis and biological evaluation
  作者：Dieter Hamprecht、Fabrizio Micheli、Giovanna Tedesco、Daniele Donati、Marcella Petrone、Silvia Terreni、Martyn Wood

  DOI：10.1016/j.bmcl.2006.10.034

  日期：2007.1

  Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level. (c) 2006 Elsevier Ltd. All rights reserved.