1,7-dimethyl-1H-indole-3-carbonitrile | 125818-13-5

• 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: 1,7-dimethyl-1H-indole-3-carbonitrile
• 英文别名: 1,7-Dimethylindole-3-carbonitrile
• CAS: 125818-13-5
• 化学式: C₁₁H₁₀N₂
• 分子量: 170.214
• InChiKey: PZFXFRLDKDWZRR-UHFFFAOYSA-N

物化性质

• 熔点：
  116 °C
• 沸点：
  342.4±22.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  28.7
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,7-dimethyl-1H-indole-3-carbonitrile 在 盐酸羟胺 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以16%的产率得到1,7-二甲基-1H-吲哚-3-甲酰胺肟
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021
• 作为产物：
  描述：

  1,7-二甲基-1H-吲哚-3-羧酸 在 草酰氯 、 氨 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 1,7-dimethyl-1H-indole-3-carbonitrile
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021

文献信息

• The palladium-catalyzed cyanation of indole C–H bonds with the combination of NH4HCO3 and DMSO as a safe cyanide source
  作者：Xinyi Ren、Jianbin Chen、Fan Chen、Jiang Cheng

  DOI：10.1039/c1cc11603g

  日期：——

  A palladium-catalyzed cyanation of the 3-position of indole sp2 C–H bonds by the combination of NH4HCO3 and DMSO as the “CN” source was achieved to provide aromatic nitriles in moderate to good yields with excellent regioselectivity. It represents a practical and safe cyanation method.

  实现了通过NH4HCO3和DMSO组合作为“CN”源，钯催化的吲哚3-位sp2 C–H键的氰化反应，以中等至良好的产率得到了具有优异区域选择性的芳香腈。这代表了一种实用且安全的氰化方法。
• Iron-Mediated Cyanation of Methoxybenzene, Indole, and 2-Arylpyridine C-H Bonds
  作者：Fan Chen、Guangyou Zhang、Guanglei Lv、Changduo Pan、Jiang Cheng

  DOI：10.1055/s-0031-1289883

  日期：2011.12

  An iron-mediated direct cyanation of indole and 2-arylpyridine C-H bonds is described. Notably, trimethoxybenzene reacted smoothly under the procedure, forming a C-CN bond via C-H bond cleavage without chelation assistance.

  本文描述了一种铁介导的吲哚和2-芳基吡啶C-H键的直接氰化反应。值得注意的是，三甲氧基苯在该反应过程中顺利反应，通过C-H键断裂形成C-CN键，而无需配位辅助。
• Copper-mediated C3-cyanation of indoles by the combination of amine and ammonium
  作者：Bin Liu、Jiehui Wang、Bo Zhang、Yang Sun、Lei Wang、Jianbin Chen、Jiang Cheng

  DOI：10.1039/c3cc49339c

  日期：——

  A copper-promoted C3-cyanation of both the free N–H and N-protected indoles by N,N,N′,N′-tetramethyl-ethane-1,2-diamine (TMEDA) and ammonium is achieved. The iminium ion acts as the intermediate in this transformation, which is sequentially electrophilically attacked by indole and H2O followed by hydrolyzation to form the aldehyde. Then the reaction between the aldehyde and ammonium afforded nitriles. The reaction employs O2 as a clean oxidant with good efficiency and functional group tolerance. Thus, it represents a facile and safe procedure leading to 3-cyano indoles.

  通过 N,N,N′,N′-四甲基乙烷-1,2-二胺（TMEDA）和铵的促进，铜催化的 C3-氰化反应成功实现了游离 N–H 和 N-保护吲哚的氰化。亚胺离子作为该转化过程中的中间体，依次受到吲哚和 H2O 的亲电攻击，然后水解形成醛。接着，醛与铵的反应生成腈。这一反应采用 O2 作为清洁氧化剂，具有良好的效率和官能团耐受性。因此，它代表了一种简便且安全的步骤，能够产生 3-氰吲哚。
• Five-membered ring systems with bonded azacyclic ring substituents
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0328200A1

  公开（公告）日：1989-08-16

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: in which: R' represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -s alkoxy or C1 -6 alkylcarbonyl; V represents nitrogen, - CH or - C -; and W represents oxygen, sulphur or - NR8, in which R8 represents hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: . a) a non-aromatic azacyclic or azabicyclic ring system; or b) a group of formula -NRaRb, in which Ra and Rb independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-s alkynyl or aryl(C1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了式 I 的化合物或其盐或原药： 其中圆点代表五元环任意位置上的一个或两个双键； X、Y和Z独立地代表氧、硫、氮或碳，条件是X、Y和Z中至少有一个代表氧、硫或氮； 其中 R'代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 炔基、C1-6 烷氧基、羟基（C1-6）烷基、卤素、氨基、氰基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-s 烷氧基或 C1-6 烷基羰基； V 代表氮、- CH 或 - C -；以及 W 代表氧、硫或- NR8，其中 R8 代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； E 代表键或含有 1 至 5 个碳原子的直链或支链亚烷基链，可选择被羟基或苯基取代； 以及 F 代表 a) 非芳氮杂环或氮杂环环系；或 b) 式-NRaRb 的基团，其中 Ra 和 Rb 独立代表氢、C1-6 烷基、C2-6 烯基、C2-s 烷炔基或芳基（C1-6）烷基。这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑、戒酒或戒毒、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心和呕吐以及先天性和老年性痴呆。
• Spirocyclic compounds incorporating five-membered rings with two heteroatoms
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0337547A1

  公开（公告）日：1989-10-18

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted line represents an optional chemical bond in one of the two possible positions; A represents a group of formula II: in which R1 represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, benzyloxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, nitro, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -6 alkoxy or C1-6 alkylcarbonyl; V represents nitrogen, -CH or -C-; and W represents oxygen, sulphur or -NR8, in which R8 represents hydrogen, C, -6 alkyl, C2-6 alkenyl or C2-6 alkynyl; two of X, Y and Z are the same or different and each represents oxygen, sulphur or nitrogen; and the remaining group X, Y or Z is carbon, or Y is carbonyl (C = 0); and Q is the residue of an azacyclic or azabicyclic ring system; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal or,dependence; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; moyement disorders; and presenile and senile dementia,

  本发明提供一种式 I 的化合物或其盐或原药： 其中虚线代表两个可能位置之一的任选化学键；A 代表式 II 的基团： 其中 R1 代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 烷炔基、C1-6 烷氧基、苄氧基、羟基（C1-6）烷基、卤素、氨基、氰基、硝基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-6 烷氧基或 C1-6 烷基羰基； V 代表氮、-CH 或-C-；以及 W 代表氧、硫或-NR8，其中 R8 代表氢、C, -6 烷基、C2-6 烯基或 C2-6 烷炔基； X、Y 和 Z 中的两个相同或不同，各自代表氧、硫或氮；其余基团 X、Y 或 Z 为碳，或 Y 为羰基（C = 0）；以及 Q 是氮杂环或氮双环环系统的残基；这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑症、酒精或药物戒断或依赖症、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食管炎和胀气）、偏头痛、恶心和呕吐、精神错乱以及先天性和老年性痴呆症、