[6-fluoro-1-(4-toluenesulfonyl)indol-3-yl]carboxaldehyde | 863407-41-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [6-fluoro-1-(4-toluenesulfonyl)indol-3-yl]carboxaldehyde
• 英文别名: 6-Fluoro-1-(4-methylphenyl)sulfonylindole-3-carbaldehyde
• CAS: 863407-41-4
• 化学式: C₁₆H₁₂FNO₃S
• 分子量: 317.341
• InChiKey: FTDFAAGCUGVNPN-UHFFFAOYSA-N

物化性质

• 沸点：
  519.9±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [6-fluoro-1-(4-toluenesulfonyl)indol-3-yl]carboxaldehyde 在 lithium aluminium tetrahydride 、 palladium diacetate 、 三乙酰氧基硼氢化钠 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 生成 {(1R,2R)-2-[6-Fluoro-1-(toluene-4-sulfonyl)-1H-indol-3-yl]-cyclopropylmethyl}-dimethyl-amine
  参考文献：
  名称：

  Conformationally Restricted Homotryptamines. 2. Indole Cyclopropylmethylamines as Selective Serotonin Reuptake Inhibitors

  摘要：

  A series of indole cyclopropylmethylamines were found to be potent serotonin reuptake inhibitors. Nitrile substituents at the 5 and 7 positions of the indole ring gave high affinity for hSERT, and the preferred cyclopropane stereochemistry was determined to be (1S,2S)-trans. The cis-cyclopropanes had 20- to 30-fold less affinity than the trans, and the preferred cis stereochemistry was (1R,2S)-cis. Substitution of the indole N-1 position with methyl or ethyl groups gave a 10- to 30-fold decrease in affinity for hSERT, suggesting either a hydrogen-bonding interaction or limited steric tolerance in the region of the indole nitrogen. Compound (+)-12a demonstrated potent hSERT binding (K-i = 0.18 nM) in vitro and was more than 1000-fold less potent at hDAT, hNET, 5-HT1A, and 5-HT6. In vivo, (+)-12a produced robust, dose-dependent increases in extracellular serotonin in rat frontal cortex typical of a selective serotonin reuptake inhibitor. The maximal response produced by (+)-12a was similar to that of fluoxetine but at an approximately 10-fold lower dose.

  DOI：

  10.1021/jm0503291
• 作为产物：
  描述：

  6-氟吲哚 在 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.83h， 生成 [6-fluoro-1-(4-toluenesulfonyl)indol-3-yl]carboxaldehyde
  参考文献：
  名称：

  通过瞬态导向基团策略钯催化羧酸对吲哚进行区域选择性 C4-H 酰氧基化

  摘要：

  开发一种有效的 C4 氧基取代吲哚合成方法是一项有吸引力但具有挑战性的任务。在此，我们报告了一种用于吲哚直接 C4-H 酰氧基化的通用钯催化 TDG 方法。该协议具有原子和步骤经济性、优异的区域选择性和良好的官能团耐受性。此外，该反应可以适应一系列羧酸，包括苯甲酸、苯乙酸和脂肪酸。

  DOI：

  10.1021/acs.orglett.3c03568

文献信息

• A highly efficient method for the construction of cyclopropane-containing dihydroindole derivatives from indolemethylenecyclopropanes with DIAD and DEAD
  作者：Mintao Chen、Wenqing Zang、Yin Wei、Min Shi

  DOI：10.1039/c9ob02520k

  日期：——

  A highly efficient method for the construction of cyclopropane-containing dihydroindole derivatives from indolemethylenecyclopropanes with DIAD and DEAD has been disclosed. The transformation could occur under catalyst-free conditions at ambient temperature to afford dihyroindole derivatives in good yields. It has been proved that the strained moiety of methylenecyclopropane in the substrate of in

  已经公开了一种利用DIAD和DEAD由吲哚亚甲基环丙烷构造含环丙烷的二氢吲哚衍生物的高效方法。该转化可以在室温下在无催化剂的条件下发生，以良好的产率提供二氢吲哚衍生物。已经证明吲哚亚甲基环丙烷底物中亚甲基环丙烷的应变部分是关键的，并且DFT计算显示该反应通过两步途径进行。
• Rhodium(I)‐Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles
  作者：Xiaoxun Li、Haibo Xie、Xiaoning Fu、Ji‐tian Liu、Hao‐yuan Wang、Bao‐min Xi、Peng Liu、Xiufang Xu、Weiping Tang

  DOI：10.1002/chem.201602088

  日期：2016.7.18

  A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4–C7 positions of indoles and related heterocycles.

  苯环的从头合成可以使用统一的羰基苯环化策略，从简单的杂芳基炔丙酸酯制备各种范围的杂环，包括吲哚，苯并呋喃，苯并噻吩，咔唑和二苯并呋喃。可以将多个取代基轻松引入吲哚和相关杂环的C4-C7位。
• [EN] ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS CALCIUM OR SODIUM CHANNEL BLOCKERS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE SUBSTITUÉS PAR ARYLE COMME INHIBITEURS DES CANAUX CALCIQUES OU SODIQUES
  申请人：RAQUALIA PHARMA INC

  公开号：WO2010137351A1

  公开（公告）日：2010-12-02

  The present invention relates to aryl substituted carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, which have blocking activities of T-type calcium channels or voltage gated sodium channels as the tetrodotoxin-sensitive (TTX-S)blockers such as NaV1.3 and NaV1.7, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels or voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels or voltage gated sodium channels are involved.

  本发明涉及式(I)或其药物可接受的盐的芳基取代羧酰胺衍生物，其具有T型钙通道或电压门控钠通道的阻断活性，如NaV1.3和NaV1.7等Tetrodotoxin敏感（TTX-S）阻断剂，适用于治疗或预防涉及T型钙通道或电压门控钠通道的疾病和紊乱。本发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及T型钙通道或电压门控钠通道的疾病中使用这些化合物和组合物的用途。
• Pd(II)-Catalyzed Transient Directing Group-Assisted Regioselective Diverse C4–H Functionalizations of Indoles
  作者：Anurag Singh、Arnab Dey、Kuntal Pal、Om Prakash Dash、Chandra M. R. Volla

  DOI：10.1021/acs.orglett.2c00320

  日期：2022.3.18

  (TDG)-assisted methodology for realizing C4 chlorination/bromination of indoles employing glycine as the TDG and NFSI as a bystanding oxidant. The use of inexpensive and commercially available CuX2 as the halide source is the key highlight of this protocol. Furthermore, the TDG methodology was also extended to accessing C4 acetoxylated indoles employing acetic acid as the acetate source and 1-fluoro-2,4

  开发一种合理的策略来实现吲哚的位点选择性 C4-H 卤化是一项有吸引力但具有挑战性的任务。在此，我们公开了一种 Pd(II) 催化的瞬态导向基团 (TDG) 辅助方法，用于实现吲哚的 C4 氯化/溴化，采用甘氨酸作为 TDG，NFSI 作为备用氧化剂。使用廉价且市售的 CuX 2作为卤化物源是该协议的主要亮点。此外，TDG 方法还扩展到使用乙酸作为乙酸盐源和 1-fluoro-2,4,6-trimethylpyridinium triflate 作为氧化剂的 C4 乙酰氧基化吲哚。
• ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS CALCIUM OR SODIUM CHANNEL BLOCKERS
  申请人：Inoue Tadashi

  公开号：US20120101105A1

  公开（公告）日：2012-04-26

  The present invention relates to aryl substituted carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, which have blocking activities of T-type calcium channels or voltage gated sodium channels as the tetrodotoxin-sensitive (TTX-S) blockers such as Na v1.3 and Na v1.7 , and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels or voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels or voltage gated sodium channels are involved.

  本发明涉及公式(I)或其药学上可接受的盐的芳基取代羧酰胺衍生物，其具有T型钙通道或电压门控钠通道的阻滞活性，如Nav1.3和Nav1.7等Tetrodotoxin敏感(TTX-S)阻滞剂，并且在涉及T型钙通道或电压门控钠通道的疾病或疾病的治疗或预防中有用。本发明还涉及包含这些化合物的制药组合物以及在涉及T型钙通道或电压门控钠通道的疾病或疾病的预防或治疗中使用这些化合物和组合物的用途。