4-chloro-1,3-dihydro-1-methyl-2H-indol-2-one | 158719-40-5

• 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: 4-chloro-1,3-dihydro-1-methyl-2H-indol-2-one
• 英文别名: 4-chloro-1-methyl-1,3-dihydro-indol-2-one；4-Chloro-1-methylindolin-2-one；4-chloro-1-methyl-3H-indol-2-one
• CAS: 158719-40-5
• 化学式: C₉H₈ClNO
• 分子量: 181.622
• InChiKey: YBOFOUDWAVEWHL-UHFFFAOYSA-N

物化性质

• 沸点：
  400.1±45.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-chloro-1,3-dihydro-1-methyl-2H-indol-2-one 在 tetraphosphorus decasulfide 、 air 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 dithiobis(1H-indole-3-carboxamide) deriv. 10b
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016
• 作为产物：
  描述：

  4-氯靛红 在 sodium hydride 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.25h， 生成 4-chloro-1,3-dihydro-1-methyl-2H-indol-2-one
  参考文献：
  名称：

  3-Carboxamide oxindoles 作为 1,3-C,N-双亲核试剂，用于高度非对映选择性合成含有 CF3 的螺-δ-内酰胺 oxindoles，在螺碳原子的邻位具有酰基

  摘要：

  通过3-羧酰胺羟吲哚和α,β-不饱和三氟甲基酮的Michael/ N-半缩酮化级联反应，建立了一种简单有效的合成δ-内酰胺稠合羟吲哚的策略。在温和的条件下，以中等至良好的收率和优异的非对映选择性获得了多种结构新颖的含有CF 3的螺-δ-内酰胺羟吲哚，其特征是在螺碳原子的邻位具有酰基。这项工作代表了系统研究 3-羧酰胺羟吲哚作为 1,3-C,N 双亲核试剂的第一个例子。

  DOI：

  10.1016/j.tetlet.2021.153426

文献信息

• [EN] 5-PYRIDIN-3-YL-1,3-DIHYDRO-INDOL-2-ON DERIVATIVES AND THEIR USE AS MODULATORS OF ALDOSTERONE SYNTHASE AND/OR CYP11B1<br/>[FR] DÉRIVÉS DE 5-PYRIDIN-3-YL-1,3-DIHYDRO-INDOL-2-ON ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'ALDOSTÉRONE SYNTHASE ET/OU DE LA CYP11B1
  申请人：NOVARTIS AG

  公开号：WO2010130794A1

  公开（公告）日：2010-11-18

  The present invention provides a compound a formula (I); or a pharmaceutically acceptable salt thereof, wherein: X is CH2, O, S or-NR1; each R1 are independently C1-7alkyl or C3-8cycloalkyl; each of R2 and R6 are independently hydrogen, halogen, cyano, C1-7alkyl, hydroxy-C1-7alkyl, -OR7, C3-8cycloalkyl, halo-C1-7alkyl or -CH2-NR8-SO2-R10; R3 and R4 are independently hydrogen, halogen or cyano; R5 is hydrogen, C1-2alkyl, halogen, cyano, hydroxy, hydroxy-C1-7alkyl, hydroxy-C3-8 cycloalkylalkyl, C1-7alkoxy-C3-3alkyl, -OR7, C6-10aryl, heteroaryl, heterocyclyl, C3-8 cycloalkyl, halo- C1-7alkyl, -NR8R9, -CH2NR8-C(O)NR8R9, -CH2-NR6-SO2-R10, -C(O)- R10, -SO2R10, -C(O)-NR5R9 -SO2-NR8R9, -NR3C(O)-R10 -CH2CN, or -NR8-SO2-R10. Compounds of the invention may be useful in the treatment of a disorder or disease mediated by aldosterone synthase and/or 11-beta hydroxylase (CYP1 181).

  本发明提供了一种化合物的结构式(I);或其药用可接受的盐，其中：X为CH2、O、S或-NR1；每个R1独立地为C1-7烷基或C3-8环烷基；每个R2和R6独立地为氢、卤素、氰基、C1-7烷基、羟基-C1-7烷基、-OR7、C3-8环烷基、卤基-C1-7烷基或-CH2-NR8-SO2-R10；R3和R4独立地为氢、卤素或氰基；R5为氢、C1-2烷基、卤素、氰基、羟基、羟基-C1-7环烷基、羟基-C3-8环烷基、C1-7烷氧基-C3-3烷基、-OR7、C6-10芳基、杂环芳基、杂环基、C3-8环烷基、卤基-C1-7烷基、-NR8R9、-CH2NR8-C(O)NR8R9、-CH2-NR6-SO2-R10、-C(O)-R10、-SO2R10、-C(O)-NR5R9-SO2-NR8R9、-NR3C(O)-R10-CH2CN或-NR8-SO2-R10。本发明的化合物可能在治疗由醛固酮合酶和/或11-β羟化酶（CYP1 181）介导的疾病或紊乱中有用。
• Hydrogen-Bond-Directed Formal [5 + 1] Annulations of Oxindoles with Ester-Linked Bisenones: Facile Access to Chiral Spirooxindole δ-Lactones
  作者：Shuai Zhao、Jun-Bing Lin、Yuan-Yuan Zhao、Yong-Min Liang、Peng-Fei Xu

  DOI：10.1021/ol500547e

  日期：2014.3.21

  A novel bifunctional thiourea catalyzed formal [5 + 1] cycloaddition of oxindoles and ester-linked bisenones was successfully developed. This strategy involves two sequential Michael additions, leading to spirooxindole δ-lactones with three contiguous stereocenters including an all-carbon quaternary center with high diastereo- and enantioselectivites. In addition, a remarkable N-substituent effect

  一种新型的双功能硫脲催化了羟吲哚和酯连接的双硒酮的正式[5 +1]环加成反应。该策略涉及两个连续的迈克尔加成，从而产生具有三个连续立体中心的螺环吲哚δ-内酯，包括具有高非对映体和对映体选择性的全碳四元中心。另外，在反应性和选择性上观察到了显着的N-取代作用。
• Cinchona-alkaloid-catalyzed enantioselective hydroxymethylation of 3-fluorooxindoles with paraformaldehyde
  作者：Jian-bo Zhao、Xinfeng Ren、Bu-quan Zheng、Jian Ji、Zi-bin Qiu、Ya Li

  DOI：10.1016/j.jfluchem.2018.09.004

  日期：2018.11

  Cinchona-alkaloid-catalyzed hydroxymethylation of 3-fluorooxindoles using paraformaldehyde as the C1 unit was achieved. A wide range of 3-fluorooxindoles was successfully reacted to give the corresponding 3-fluoro-3-hydroxymethyloxindoles with high efficiency and moderate to good enantioselectivity.

  使用多聚甲醛作为C1单元，实现了金鸡纳生物碱催化的3-氟代吲哚的羟甲基化反应。各种各样的3-氟代羟吲哚成功地反应生成了相应的3-氟-3-羟甲基羟甲基吲哚，具有高效率和中等至良好的对映选择性。
• Detrifluoroacetylative in Situ Generation of Free 3-Fluoroindolin-2-one-Derived Tertiary Enolates: Design, Synthesis, and Assessment of Reactivity toward Asymmetric Mannich Reactions
  作者：Chen Xie、Lijun Zhang、Wanxing Sha、Vadim A. Soloshonok、Jianlin Han、Yi Pan

  DOI：10.1021/acs.orglett.6b01516

  日期：2016.7.1

  situ generation of a new type of fluorinated amide enolates derived from 3-fluoroindolin-2-one and their asymmetric Mannich additions with sulfinylaldimines bearing fluoroalkyl groups is reported, which afforded α-fluoro-β-(fluoroalkyl)-β-aminoindolin-2-ones containing C–F quaternary stereogenic centers with excellent yields and high diastereoselectivities.

  据报道，发现了由三氟吲哚-2-酮衍生的新型氟化酰胺烯酸酯的三氟乙酰化原位生成及其与带有氟代烷基的亚磺酰基亚胺的不对称曼尼希加成反应，从而制得α-氟代-β-（氟代烷基）-β。 -aminoindolin-2-ones包含CF四元立体构象中心，产率高，非对映选择性高。
• Copper powder-catalyzed chelation-assisted cascade reaction of o-chloroarylacetic acids with amines under solvent- and ligand-free conditions: synthesis of oxindoles
  作者：Jiang-Sheng Li、Guo-Qin Chen、Qian Yang、Zhi-Wei Li、Ci-Zhi Liu、Peng-Mian Huang

  DOI：10.1039/c7ra08123e

  日期：——

  An efficient method to construct oxindole scaffolds from o-chloroarylacetic acids/esters with amines has been explored. This cascade protocol involves the in situ generation of o-aminoarylacetic acid derivatives by the copper powder catalyzed and weak O-chelation assisted Ullmann amination of unactivated C–Cl bonds under air, and solvent-/ligand-free conditions followed by annulative N-acylation.

  已经探索了由邻氯代乙酸/酯与胺一起构建羟吲哚骨架的有效方法。该级联方案涉及在空气中，在无溶剂/无配体的条件下，通过铜粉催化的铜粉催化和弱O-螯合辅助未激活的C-Cl键的Ullmann胺化原位生成邻氨基芳酸衍生物，然后进行环化N-酰化。