7-Methoxy-N-methyl-oxindol | 7699-23-2

• 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: 7-Methoxy-N-methyl-oxindol
• 英文别名: 7-Methoxy-1-methylindolin-2-one；7-methoxy-1-methyl-3H-indol-2-one
• CAS: 7699-23-2
• 化学式: C₁₀H₁₁NO₂
• 分子量: 177.203
• InChiKey: QDBHDDVJPQBXBZ-UHFFFAOYSA-N

物化性质

• 熔点：
  101-102 °C
• 沸点：
  393.4±42.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-Methoxy-N-methyl-oxindol 以78%的产率得到1-methyl-7-methoxy-2-indolinethione
  参考文献：
  名称：

  Novel tricyclic indole compound

  摘要：

  本发明涉及一般式为：##STR1## 的化合物，其中A、B、G、D可以相同或不同，分别表示氢原子或卤素原子、低级烷氧基或者选择性地带有一个或多个卤素原子的低级烷基；X表示氢原子、线性或支链低级烷基或者SO.sub.2 E基团，其中E表示线性或支链低级烷基或者选择性地带有一个线性或支链低级烷基取代的芳基基团；T表示氢原子或低级烷基；R.sub.3表示氢原子或线性或支链低级烷基或者选择性地带有一个或多个线性或支链低级烷基取代的芳基基团；n和m可以相同或不同，分别表示0或1；R.sub.1和R.sub.2可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sup.1和R.sup.2与它们连接的氮原子一起形成饱和或不饱和的、单环或双环的含氮杂环系统，每个环都是5或6元环，可以选择性地包含来自氮、氧或硫的其他杂原子，并且可以选择性地带有一个或多个线性或支链低级烷基或烷氧基取代的芳基基团，或者带有一个或多个本身可以选择性地带有一个或多个低级烷基、低级烷氧基或三氟甲基基团或者选择性地带有一个或多个卤素原子的芳基基团，或者选择性地，R.sup.1表示一个基团##STR2## 其中R.sub.4、R.sub.5和R.sub.6可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sub.4和R.sub.5一起形成(CH.sub.2).sub.p的桥，p在2到4之间，或选择性地，R.sub.1表示一个二苯并[a,d]环庚-5-基团，R.sub.2表示氢原子，必要时，它们的异构体以及它们与药学上可接受的酸形成的加合物。药物制品。

  公开号：

  US05030646A1
• 作为产物：
  描述：

  2-甲氧基-N-甲基苯胺 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 7-Methoxy-N-methyl-oxindol
  参考文献：
  名称：

  Photochemical synthesis of 1,2,3,4-tetrahydroisoquinolin-3-ones and oxindoles from N-chloroacetyl derivatives of benzylamines and anilines. Role of intramolecular exciplex formation and cis conformation of amide bonds.

  摘要：

  虽然苄胺（2、8）和苯胺（21、25、29）的 N-氯乙酰基衍生物在高压汞灯照射下会迅速消失，但并没有发生六元和五元内酰胺的光环化反应。对不同烷基链长度的 N-氯乙酰基-(3, 4-二甲氧基苯基)-烷基胺的荧光淬灭和消失量子产率的测量表明，烷基链越短，形成复合物的效率越高。因此，光环化失败似乎是由于苄胺和苯胺衍生物中酰胺键的反式构象造成的。因此，N-烷基-N-氯乙酰基苄胺（11、13、15、17、19）在辐照下很容易生成相应的 1、2、3、4-四氢异喹啉-3-酮（12、14、16、18、20）。通过 N-烷基-N-氯乙酰苯胺（35、37、39、42、45）的光环化反应，也同样合成了氧化吲哚（36、38、40、41、43、46）。

  DOI：

  10.1248/cpb.29.128

文献信息

• Synthesis of Oxindole Derivatives via Intramolecular C–H Insertion of Diazoamides Using Ru(II)-Pheox Catalyst
  作者：Nga Phan Thi Thanh、Huong Dang Thi Thu、Masaya Tone、Hayato Inoue、Seiji Iwasa

  DOI：10.1016/j.tet.2020.131481

  日期：2020.10

  This work presented the efficient intramolecular aromatic C–H insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products

  这项工作提出了重氮乙酰胺分子内芳香族C–H的有效插入。在Ru催化剂的存在下，通过分子内C–H插入反应，将1a – 1o重氮化合物（1k除外）转化为相应的羟吲哚。在区域选择性方面，Ru-Pheox催化剂在这种转化中表现出很高的效率，以极佳的收率（99％）生产出所需的产物。Ru催化剂的效率达到580（TON）和156min -1（TOF）。
• Synthesis of Substituted Oxindoles from α-Chloroacetanilides via Palladium-Catalyzed C−H Functionalization
  作者：Edward J. Hennessy、Stephen L. Buchwald

  DOI：10.1021/ja037546g

  日期：2003.10.1

  A novel method for the synthesis of oxindoles is described. In the presence of catalytic palladium acetate and 2-(di-tert-butylphosphino)biphenyl, α-chloroacetanilides are converted to oxindoles in good to excellent yields with high functional group compatibility using triethylamine as a stoichiometric base. The cyclization is highly regioselective, obviating the need for prefunctionalized arenes.

  描述了一种合成羟吲哚的新方法。在催化乙酸钯和 2-（二叔丁基膦）联苯的存在下，使用三乙胺作为化学计量碱，α-氯乙酰苯胺以良好至极好的收率转化为羟吲哚，并具有高官能团相容性。环化具有高度区域选择性，无需预官能化芳烃。讨论了可能的反应机理途径。
• ISATIN DERIVATIVES, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE THEREOF
  申请人：Horne David A.

  公开号：US20130225637A1

  公开（公告）日：2013-08-29

  One aspect of the invention relates to novel isatin derivative compounds and the pharmaceutical composition thereof. Another aspect of the invention relates to methods of using the isatin derivative compounds disclosed herein and the pharmaceutical compositions thereof. In certain embodiments, the method is used to treat a cancer or a tumor in a subject including, without limitation, prostate cancer, melanoma, pancreatic cancer, ovarian cancer, and lymphoma. In certain embodiment, the method is used to treat a condition in a subject that can be regulated by the activation of one or more proteins such as EGFR, Erk1/2, Her2/Neu, Jak2, Src, Stat3, Akt, Cyclin B1, and Cdc25C. In certain embodiment, the method is used to treat a condition in a subject that can be regulated by the disruption of microtubule formations.

  该发明的一个方面涉及新型异喹啉衍生物化合物及其药物组合物。该发明的另一个方面涉及使用本文披露的异喹啉衍生物化合物和其药物组合物的方法。在某些实施例中，该方法用于治疗受试者中的癌症或肿瘤，包括但不限于前列腺癌、黑色素瘤、胰腺癌、卵巢癌和淋巴瘤。在某些实施例中，该方法用于治疗受试者中可以通过激活EGFR、Erk1/2、Her2/Neu、Jak2、Src、Stat3、Akt、Cyclin B1和Cdc25C等一个或多个蛋白质来调节的疾病。在某些实施例中，该方法用于治疗受试者中可以通过破坏微管形成来调节的疾病。
• Palladium-Catalyzed Amidation by Chemoselective C(sp3)H Activation: Concise Route to Oxindoles Using a Carbamoyl Chloride Precursor
  作者：Chihiro Tsukano、Masataka Okuno、Yoshiji Takemoto

  DOI：10.1002/anie.201108889

  日期：2012.3.12

  synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad2PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp3)H activation proceeded in the presence of a C(sp2)H bond. Ad=adamantyl.

  颇为选择：一个新的战略是为各种羟吲哚从氨基甲酰氯综合方法。在最佳反应条件下，以Ad 2 PBu为配体，t BuCONHOH为添加剂，并在CO气氛下，在C（sp 2）H键的存在下进行选择性C（sp 3）H活化。Ad =金刚烷基。
• 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)
  作者：Gordon W. Rewcastle、Brian D. Palmer、Ellen M. Dobrusin、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm00039a016

  日期：1994.6

  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.