(R)-3-[(1-甲基-2-吡咯烷基)甲基]-1H-吲哚 | 143322-55-8

• 物质功能分类: 有机原料 - 杂环化合物
• 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
• 中文名称: (R)-3-[(1-甲基-2-吡咯烷基)甲基]-1H-吲哚
• 英文名称: (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole
• 英文别名: (R)-3-(1-methylpyrrolidin-3-ylmethyl)-1H-indole；(R)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole；3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole；(R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole；3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indole
• CAS: 143322-55-8
• 化学式: C₁₄H₁₈N₂
• 分子量: 214.31
• InChiKey: HCTCDEAMCNSARD-GFCCVEGCSA-N

物化性质

• 熔点：
  140-142°C
• 沸点：
  365.0±15.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）和甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-3-[(1-甲基-2-吡咯烷基)甲基]-1H-吲哚 、 5-溴噻吩-2-磺酰氯 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 生成 1-(5-Bromo-thiophene-2-sulfonyl)-3-((R)-1-methyl-pyrrolidin-2-ylmethyl)-1H-indole
  参考文献：
  名称：

  Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists

  摘要：

  Several series of conformationally constrained N-1-arylsulfonyltryptamine derivatives were prepared and tested for 5-HT6 receptor binding affinity and ability to modulate cAMP production in a cyclase assay. The 3-piperidin-3-yl-, 3-(1-methylpyrrolidin-2-ylmethyl)-, and 3-pyrrolidin-3-yl-1H-indole arrays (8-13) appear to be able to adopt a conformation that allows high affinity 5-HT6 receptor binding, while the beta-carboline array 14 binds with a significantly weaker (10- to 100-fold) affinity. N-1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole 9a is a high affinity full agonist with EC50 = 24 nM. Several of the N-1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)- 11r, (S)- 11t; IC50 = 0.8, 1.0 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.028
• 作为产物：
  描述：

  (R)-3-[(N-benzyloxycarbonylpyrrolidin-2-yl)carbonyl]-1H-indole 生成 (R)-3-[(1-甲基-2-吡咯烷基)甲基]-1H-吲哚
  参考文献：
  名称：

  Pyrrolidine-indole compounds having 5-HT.sub.6 affinity

  摘要：

  本文描述了与5-HT.sub.6受体亲和力的化合物，其具有以下一般公式：##STR1##其中：R.sup.1选自由H和C.sub.1-4烷基组成的群体；R.sup.2选自由H、C.sub.1-4烷基和苄基组成的群体；R.sup.3选自由COR.sup.5、SO.sub.2R.sup.5、CONHC.sub.1-4烷基和C(S)SR.sup.6组成的群体；R.sup.4a选自由H、OH、卤素、C.sub.1-4烷基和C.sub.1-4烷氧基组成的群体；R.sup.4b选自由H、羟基、卤素、C.sub.3-7环烷氧基、C.sub.1-4烷氧基、C.sub.1-4烷基、苄氧基、苯氧基、三氟甲基、三氟甲氧基和乙烯基组成的群体；R.sup.4c选自由H、OH、卤素、C.sub.1-4烷基和C.sub.1-4烷氧基组成的群体；R.sup.4d选自由H、OH、卤素、C.sub.1-4烷基和C.sub.1-4烷氧基组成的群体；R.sup.5选自由苯基、吡啶基、噻吩基、喹啉基和萘基，这些基团可以选择性地用1-4个来自C.sub.1-4烷氧基、C.sub.1-4烷基、卤素、硝基、三氟甲基、三氟甲氧基、1,2-亚甲二氧基、C.sub.1-4烷基羰基、C.sub.1-4烷氧羰基和C.sub.1-4烷基硫代基的取代基取代；R.sup.6选自由C.sub.1-4烷基、烯丙基、丙炔基和可以选择性取代的苄基，其中苄基可以选择性地用1-4个来自氰基、C.sub.1-4烷基和卤素的取代基取代。还描述了将这些化合物用作药物治疗5-HT.sub.6受体受到影响的精神分裂症等疾病的适应症。

  公开号：

  US06100291A1

文献信息

• Salts of (R)-5-(2phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole, 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole and of eletriptan
  申请人：KANSAL Vinod Kumar

  公开号：US20090299077A1

  公开（公告）日：2009-12-03

  The present invention relates to salts of (R)-5-(2-phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole of the formula: wherein HX is an acid selected from para-toluene sulfonic acid, benzene sulphonic acid, trifluoroacetic acid, methane sulphonic acid, formic acid and succinic acid; and to processes of preparing and using such salts.

  这项发明涉及以下化学式的(R)-5-(2-苯磺酰乙烯基)-3-(N-甲基吡咯烷-2-基甲基)-1H-吲哚的盐： 其中HX是从对甲苯磺酸、苯磺酸、三氟乙酸、甲磺酸、甲酸和琥珀酸中选择的酸；以及制备和使用这种盐的方法。
• PROCESS FOR PREPARATION OF ELETRIPTAN AND SALT THEREOF
  申请人：Sathe Dhananjay Govind

  公开号：US20120071669A1

  公开（公告）日：2012-03-22

  The present invention relates to an improved process for the preparation of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole or pharmaceutically acceptable salts thereof, particularly 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole hydrobromide (Eletriptan hydrobromide). The present invention further relates to novel polymorphs of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethenyl]-1H-indole hydrobromide and process for preparation thereof.

  本发明涉及一种改进的制备3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙基]-1H-吲哚或其药学上可接受的盐，特别是3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙基]-1H-吲哚溴化氢盐（依那曲坦溴化氢盐）。本发明还涉及3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙烯基]-1H-吲哚溴化氢盐的新晶型及其制备方法。
• Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide
  作者：Suri Babu Madasu、Nagaji Ambabhai Vekariya、M N V D Hari Kiran、Badarinadh Gupta、Aminul Islam、Paul S Douglas、Korupolu Raghu Babu

  DOI：10.3762/bjoc.8.162

  日期：——

  Eletriptan hydrobromide (1) is a selective serotonin (5-HT(1)) agonist, used for the acute treatment of the headache phase of migraine attacks. During the manufacture of eletriptan hydrobromide the formation of various impurities were observed and identified by LC-MS. To control the formation of these impurities during the preparation of active pharmaceutical ingredients, the structure of the impurities

  Eletriptan hydrobromide (1) 是一种选择性血清素 (5-HT(1)) 激动剂，用于偏头痛发作的头痛阶段的急性治疗。在氢溴酸依曲普坦的生产过程中，通过 LC-MS 观察并鉴定了各种杂质的形成。为了在活性药物成分的制备过程中控制这些杂质的形成，必须了解杂质的结构。通过使用各种光谱技术，即质谱、FTIR、(1)H NMR、(13)C NMR/DEPT，制备和表征了依曲普坦氢溴酸盐合成的主要杂质，并通过共注射在HPLC中进一步确认。本研究将对高纯度依曲普坦氢溴酸盐相关化合物的合成有很大帮助。
• Indole derivatives
  申请人：Pfizer Inc

  公开号：US05559129A1

  公开（公告）日：1996-09-24

  Compounds of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.

  该公式化合物 ##STR1## 中，其中R.sub.1、R.sub.2、R.sub.3、X和n如权利要求中所定义，以及其药用可接受盐是新的。这些化合物是有用的精神治疗药物，是有效的血清素(5-HT.sub.1)激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集簇头痛、偏头痛、疼痛、慢性阵发性半头痛和与血管疾病相关的头痛，以及其他由血清素神经递质缺乏引起的疾病。这些化合物还可用作中枢作用降压药和扩血管剂。还公开了通过过渡金属催化的二卤代中间体环化形成吲哚的方法。
• Process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole
  申请人：Bednar Roman

  公开号：US20080319205A1

  公开（公告）日：2008-12-25

  The invention encompasses a process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole comprising reacting (R)-2-(5-bromo-1H-indole-3-carbonyl)-pyrrolidine-1-carboxylic acid benzyl ester with a reducing agent selected from the group consisting of sodium dihydro-bis(2-methoxyethoxy)aluminate, lithium tris[(3-ethyl-3-pentyl)oxy]aluminohydride, lithium tri-tert-butoxyaluminum hydride and diisobutylaluminium hydride. 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole is a key intermediate for preparing eletriptan and its salts thereof.

  本发明涵盖了一种制备5-溴-3-[(R)-1-甲基吡咯烷-2-基甲基]-1H-吲哚的过程，包括将(R)-2-(5-溴-1H-吲哚-3-羧酰基)-吡咯烷-1-羧酸苄酯与从钠双(2-甲氧基乙氧基)铝酸盐、三乙基-三戊基氧基铝氢化物、三叔丁氧基铝氢化铝和叔丁基铝氢化铝中选择的还原剂反应。5-溴-3-[(R)-1-甲基吡咯烷-2-基甲基]-1H-吲哚是制备依曲普坦及其盐的关键中间体。