3-乙基-1,5,6,7-四氢-2-甲基-4H-吲哚-4-酮 | 6116-76-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 吲哚类化合物
• 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: 3-乙基-1,5,6,7-四氢-2-甲基-4H-吲哚-4-酮
• 中文别名: 2-甲基-3-乙基-4-氧代-4,5,6,7-四氢吲哚；3-乙基-2-甲基-1,5,6,7-四氢吲哚-4-酮
• 英文名称: 3-ethyl-2-methyl-4,5,6,7-tetrahydroindol-4-one
• 英文别名: 2-methyl-3-ethyl-4-oxo-4,5,6,7-tetrahydroindole；3-ethyl-2-methyl-1,5,6,7-tetrahydroindol-4-one
• CAS: 6116-76-3
• 化学式: C₁₁H₁₅NO
• mdl: MFCD00005605
• 分子量: 177.246
• InChiKey: RZUQNFAPFIHYCR-UHFFFAOYSA-N

物化性质

• 熔点：
  183℃
• 沸点：
  353.8±31.0 °C(Predicted)
• 密度：
  1.106
• 溶解度：
  可溶于氯仿、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  32.9
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090
• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  3-乙基-1,5,6,7-四氢-2-甲基-4H-吲哚-4-酮 在 肼 作用下， 反应 6.5h， 以94%的产率得到bis<3-ethyl-2-methyl-4,5,6,7-tetrahydroindol-4-ylidene>hydrazine
  参考文献：
  名称：

  Hydrazine-mediated one-pot amination-oxidation reaction: facile synthesis of 4-amino-.beta.-carbolines and 4-aminoisoquinolines

  摘要：

  DOI：

  10.1021/jo00228a025
• 作为产物：
  描述：

  2,3-戊二酮 在 氢氧化钾 、 羟胺 、 溶剂黄146 、 锌 作用下， 反应 3.0h， 生成 3-乙基-1,5,6,7-四氢-2-甲基-4H-吲哚-4-酮
  参考文献：
  名称：

  Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers

  摘要：

  A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv 1.5 blockers. in in vitro studies, several compounds exhibited very good potency for blockade of Kv 1.5. Compound 8i showed good selectivity for blockade of Kv1.5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ventricular ERP. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.057

文献信息

• Catalytic Acceptorless Dehydrogenation of Amino Alcohols and 2-Hydroxybenzyl Alcohols for Annulation Reaction under Neutral Conditions
  作者：Akanksha M. Pandey、Naveen Kumar Digrawal、Nirmala Mohanta、Akash Bandu Jamdade、Moreshwar B. Chaudhari、Girish Singh Bisht、Boopathy Gnanaprakasam

  DOI：10.1021/acs.joc.1c00714

  日期：2021.7.2

  base-free and acceptorless Ru-catalyzed dehydrogenative approach has been developed for the synthesis of N-heterocycles by using 1,3-dicarbonyls and amino alcohols through a domino sequential enamine formation and intramolecular oxidative cyclization strategy. This unified approach is also applicable for the synthesis of O-heterocycles involving 2-hydroxybenzyl alcohol as a coupling reactant via consecutive

  开发了一种无碱和无受体的 Ru 催化脱氢方法，通过多米诺顺序烯胺形成和分子内氧化环化策略，使用 1,3-二羰基和氨基醇合成N-杂环。这种统一的方法也适用于通过连续的 C-烷基化和分子内环化步骤合成 2-羟基苯甲醇作为偶联反应物的 O-杂环。本协议适用于各种重要的生物学支架的合成，如四氢-4 H -indol-4-one、3,4-dihydroacridin-1(2 H )-one 和四氢-1 H - xanthen-使用单一催化系统的 1-ones 衍生物，即。RuH 2CO(PPh 3 ) 3。对环境无害的 H 2 O 和 H 2是该多米诺骨牌过程中唯一的副产品。此外，该报告还描述了使用醇作为烷基化伙伴的RuH 2 CO(PPh 3 ) 3 -催化的四氢-4 H-吲哚-4-酮的C3-烷基化。首次证明了无受体脱氢环化的无溶剂克级反应。一些实验研究和光谱证据为 Ru 催化的氨基醇或 2-羟基
• Conformationally Restricted Butyrophenones with Mixed Dopaminergic (D2) and Serotoninergic (5-HT2A) Affinities. Synthesis of 5-Aminoethyl and 6-Aminomethyl-4-oxotetrahydroindoles as Potential Atypical Antipsychotics.
  作者：Chiristian F. MASAGUER、Isabel CASARIEGO、Enrique RAVINA

  DOI：10.1248/cpb.47.621

  日期：——

  We describe the synthesis of 5-aminoethyl- and 6-aminomethyl-4-oxotetrahydroindoles as butyrophenone derivatives in the indole series, as potential atypical antipsychotics. The affinities of these compounds for serotonin (5-HT2A) and dopamine (D2) receptors were evaluated in vitro. The ratios of pKi's for 5-HT2A/D2 receptors may be useful for rapid screening of new compounds and assessing potential induction of extrapyramidal symptoms; ratio values ≥1.12 (Meltzer's ratio) are predictive of an atypical antipsychotic profile. Compounds 26e (QF 0408B) and 26f (QF 0409B) showed high affinity for both D2 and 5-HT2A receptors, and their MEltzer's ratios were 1.32 and 1.17 respectively, while haloperidol showed a ratio of 0.93.

  我们介绍了作为吲哚系列丁酮衍生物的 5-氨基乙基和 6-氨基甲基-4-氧代四氢吲哚的合成，它们是潜在的非典型抗精神病药物。这些化合物与血清素（5-HT2A）和多巴胺（D2）受体的亲和力在体外进行了评估。5-HT2A/D2受体的pKi比值可用于快速筛选新化合物和评估诱发锥体外系症状的可能性；比值≥1.12（Meltzer比值）可预测非典型抗精神病药的特征。化合物 26e（QF 0408B）和 26f（QF 0409B）显示出对 D2 和 5-HT2A 受体的高亲和力，它们的梅尔策尔比值分别为 1.32 和 1.17，而氟哌啶醇的比值为 0.93。
• Levorotatory molindone and the use as an antidepressant
  申请人：Endo Laboratories, Inc.

  公开号：US04065453A1

  公开（公告）日：1977-12-27

  The levorotatory enantiomer of molindone [3-ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)-indol-4(5H)-one] has been isolated and found to have significantly greater antidepressant activity than the corresponding racemate.

  摩林酮的左旋异构体[3-乙基-6,7-二氢-2-甲基-5-(吗啡啶甲基)-吲哚-4(5H)-酮]已被分离并发现其抗抑郁活性显著优于相应的混合物。
• METHODS OF PRODUCING MOLINDONE AND ITS SALTS
  申请人：SUPERNUS PHARMACEUTICALS INC.

  公开号：US20140081020A1

  公开（公告）日：2014-03-20

  The present invention is directed towards novel methods of synthesis of molindone, synthesis of the intermediates of molindone, and high-purity compositions of molindone. In particular, the invention relates to the methods of synthesis of molindone through the Mannich reaction.

  本发明涉及一种合成莫林酮的新方法，合成莫林酮的中间体以及高纯度的莫林酮组合物。特别是，本发明涉及通过曼尼希反应合成莫林酮的方法。
• PROCESS FOR PREPARATION OF MOLINDONE
  申请人：LUPIN LIMITED

  公开号：US20200262788A1

  公开（公告）日：2020-08-20

  The present invention provides process for preparation of molindone (I) comprising: a) reacting compound with cyclohexane-1,3-dione to form 2-(2-oxopentan-3-yl)cyclohexane-1,3-dione wherein X is Cl, Br or I, b) cyclizing 2-(2-oxopentan-3-yl)cyclohexane-1,3-dione to 2-methyl-3-ethyl-4-oxo-4,5,6,7-tetrahydroindole, c) reacting 2-methyl-3-ethyl-4-oxo-4,5,6,7-tetrahydroindole with morpholine and formaldehyde to give molindone (I), and d) optionally converting molindone (I) to its salt. The present invention further provides process for preparation of compound comprising: a) reacting compound with ethyl halide and another halide source to form compound wherein R is alkyl and X is Cl, Br or I; b)converting compound to compound.

  本发明提供了制备莫林酮（I）的方法，包括：a）将化合物与环己烷-1,3-二酮反应，形成2-(2-氧代戊酰基)环己烷-1,3-二酮，其中X为Cl、Br或I；b）将2-(2-氧代戊酰基)环己烷-1,3-二酮环化为2-甲基-3-乙基-4-氧代-4,5,6,7-四氢吲哚；c）将2-甲基-3-乙基-4-氧代-4,5,6,7-四氢吲哚与吗啉和甲醛反应，得到莫林酮（I）；d）可选择将莫林酮（I）转化为其盐。本发明还提供了制备化合物的方法，包括：a）将化合物与乙基卤代烃和另一卤代源反应，形成化合物，其中R为烷基，X为Cl、Br或I；b）将化合物转化为化合物。

表征谱图