4-dimethylaminomethyl-3-ethoxycarbonyl-5-hydroxy-1,2-dimethylindole | 25913-94-4

• 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-dimethylaminomethyl-3-ethoxycarbonyl-5-hydroxy-1,2-dimethylindole
• 英文别名: 4-dimethylaminomethyl-5-hydroxy-1,2-dimethyl-indole-3-carboxylic acid ethyl ester；1,2-Dimethyl-3-ethoxycarbonyl-4-dimethylaminomethyl-5-hydroxy-indol；ethyl 4-[(dimethylamino)methyl]-5-hydroxy-1,2-dimethyl-1H-indole-3-carboxylate；ethyl 4-[(dimethylamino)methyl]-5-hydroxy-1,2-dimethylindole-3-carboxylate
• CAS: 25913-94-4
• 化学式: C₁₆H₂₂N₂O₃
• mdl: MFCD01552855
• 分子量: 290.362
• InChiKey: CXCWEVZTMHDHDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  54.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  三硝基甲烷钾 、 4-dimethylaminomethyl-3-ethoxycarbonyl-5-hydroxy-1,2-dimethylindole 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.67h， 以41%的产率得到ethyl 6,7-dimethyl-2-nitro-6H-furo[3,2-e]indole-8-carboxylate
  参考文献：
  名称：

  Potassium Trinitromethanide as a 1,1-Ambiphilic Synthon Equivalent: Access to 2-Nitroarenofurans

  摘要：

  The first example of the use of potassium trinitromethanide as a 1,1-ambiphilic synthon equivalent for the construction of a benzofuran moiety mediated by triethylamine has been developed. The method tolerates a variety of functional groups on the starting quaternary ammonium salt and has been successfully extended to polysubstituted benzofurans. Formation of an o-quinone methide intermediate is postulated as a key to the mechanism of this cascade process.

  DOI：

  10.1021/jo402543s
• 作为产物：
  描述：

  聚合甲醛 、 美卡比酯 、 二甲胺 在 盐酸 、 乙醇 作用下， 以 乙醇 、 水 为溶剂， 生成 4-dimethylaminomethyl-3-ethoxycarbonyl-5-hydroxy-1,2-dimethylindole
  参考文献：
  名称：

  苯并恶嗪作为M（4）毒蕈碱受体的高度选择性拮抗剂的合成与药理作用。

  摘要：

  以前，我们在PD 102807（41）上报道其为迄今为止鉴定出的最具选择性的合成M（4）毒蕈碱拮抗剂。当时合成的41类似物没有显示亲和力和选择性的改善。但是，几种新合成的化合物在M（4）受体上显示出7倍更高的亲和力，并且比所有其他毒蕈碱受体亚型表现出至少100倍的选择性。例如，化合物28对M（4）受体显示pK（i）= 9.00的亲和力，对M（1）/ M（4）= 13183-fold，M（2）/ M（4）= 339倍，M（3）/ M（4）= 151倍和M（5）/ M（4）= 11220倍。尚未针对任何合成毒蕈碱拮抗剂或天然M（4）拮抗剂如M（4）选择性东部绿曼巴蛇毒MT3（M（4）pK（b）= 8.7）报道过这种高选择性和高亲和力。 ，M（1）/ M（4）= 40倍，M（2）/ M（4）>或= 500倍，M（3）/ M（4）>或= 500倍，以及M（5）/ M（4）>或= 500倍）。衍生物

  DOI：

  10.1021/jm011116o

文献信息

• Synthesis and some pharmacological properties of derivatives of indole and benzofuran containing the imidazole pharmacophore
  作者：S. A. Zotova、V. I. Shvedov

  DOI：10.1007/bf02220018

  日期：1994.2

  bisaminomethyl derivative is formed on heating a monomethylamino derivative with bisdimethylaminomethane in acetic acid. We attempted to use this procedure for the synthesis of benzofuran derivatives containing other aminomethyl groups in addition to the imidazolylmethyl group. However on heating compound (IX) with bisdimethylaminomethane in acetic acid the corresponding 4,6-bisdimethylamino derivative (XVII)

  鉴于有关含有咪唑药效团的化合物具有高度多样的生物活性的报道的出现[7-12]，我们合成并研究了吲哚和苯并呋喃的一些咪唑衍生物的生物特性。我们使用两种方法来获得这些化合物，即咪唑与曼尼希碱的烷基化以及咪唑与溴代烷基衍生物的反应。作为最初的曼尼希碱，我们使用 4-二甲基氨基甲基-3-乙氧基羰基-5-羟基-l,2-二甲基吲哚 (I) [5], 6br•m•-4-dimethy•amin•methy•-3-eth•xycarb• ny•-5-hydr•xy-•-methy•-2-pheny•thi•methy•ind••e (II) [1], 2-甲基(III) [4], 2苯基(IV) [2] , 2-phenoxymethyl(V), and 2-phenylthiomethyl-4-dimethylaminomethyl-3-ethoxy-carbonyl-5-hydroxybenzofuran
• One-Pot Synthesis of B-Ring <i>Ortho</i>-Hydroxylated Sappanin-Type Homoisoflavonoids
  作者：Galyna P. Mrug、Nataliia V. Myshko、Svitlana P. Bondarenko、Vitaliy M. Sviripa、Mykhaylo S. Frasinyuk

  DOI：10.1021/acs.joc.9b00814

  日期：2019.6.7

  A reliable method for the synthesis of B-ring hydroxylated homoisoflavonoids and 3-hetarylmethyl chromones has been developed. The method involves an initial oxa-Diels–Alder reaction of ortho-quinone methides generated from aryl/hetaryl-substituted ortho-(N,N-dimethylaminomethyl)phenols with (2E)-3-(N,N-dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-ones and the subsequent cascade of reactions. This

  已开发出一种可靠的合成B环羟基化的异黄酮和3-杂芳基甲基色酮的方法。该方法涉及由芳基/杂芳基取代的邻-（N，N-二甲基氨基甲基）苯酚与（2 E）-3-（N，N-二甲基氨基）-1生成的邻醌醌的初始oxa-Diels-Alder反应-（2-羟基苯基）丙-2-烯-1-酮和随后的级联反应。该合成策略避免了常规的多步骤方案，并且不需要保护羟基，因此可以容易地合成天然存在的同异类黄酮的各种芳族和杂环类似物的文库。
• An Inverse Electron Demand Azo-Diels–Alder Reaction of <i>o</i>-Quinone Methides and Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines
  作者：Dmitry V. Osipov、Vitaly A. Osyanin、Guzel’ D. Khaysanova、Elvira R. Masterova、Pavel E. Krasnikov、Yuri N. Klimochkin

  DOI：10.1021/acs.joc.8b00692

  日期：2018.4.20

  the reactions of o-quinone methide precursors with imino ethers. The reaction provides a versatile route to substituted 1,3-benzoxazines. The proposed reaction mechanism involves the generation of the o-quinone methide intermediates, imino-Diels–Alder reaction, and elimination. This cascade process is a rare example of the participation of imino ethers as dienophiles.

  我们已经研究了邻醌甲基化物前体与亚氨基醚的反应。该反应提供了取代的1，3-苯并恶嗪的通用途径。拟议的反应机制涉及邻醌甲基化物中间体的产生，亚氨基-狄尔斯-阿尔德反应和消除。这种级联过程是亚氨基醚作为亲双烯体参与的罕见例子。
• [4+2]-Cycloaddition of 1,1,3,3-tetramethylguanidine and o-quinone methides: synthesis of arene-fused 2-dimethylamino-4H-1,3-oxazines
  作者：V. A. Osyanin、D. V. Osipov、P. E. Krasnikov、V. A. Shiryaev

  DOI：10.1007/s11172-022-3673-1

  日期：2022.11

  A method for producing substituted 4H-1,3-benzoxazines and their fused derivatives bearing N,N-dimethylamino moiety in the position 2 of 4H-1,3-oxazine ring from phenolic and naphtholic Mannich bases, their iodomethylates or salicylic alcohols, and 1,1,3,3-tetramethylguanidine has been developed. This reaction is supposed to proceed via the generation of o-quinone methides followed by [4+2]-cycloaddition and elimination of dimethylamine.

  本研究开发了一种方法，用于从酚类和萘类曼尼希碱、其碘甲酸酯或水杨醇以及 1,1,3,3-四甲基胍中生产取代的 4H-1,3-苯并噁嗪及其在 4H-1,3-噁嗪环的第 2 位含有 N,N-二甲基氨基的融合衍生物。该反应应该是通过生成邻醌甲酰胺，然后进行[4+2]-环加成反应并消除二甲胺。
• Reactions of <i>o</i>-Quinone Methides with Pyridinium Methylides: A Diastereoselective Synthesis of 1,2-Dihydronaphtho[2,1-<i>b</i>]furans and 2,3-Dihydrobenzofurans
  作者：Vitaly A. Osyanin、Dmitry V. Osipov、Yuri N. Klimochkin

  DOI：10.1021/jo400621r

  日期：2013.6.7

  A simple, general route to the 1,2-dihydronaphtho[2,1-b]furans and 2,3-dihydrobenzofurans substituted at C-2 by an acyl or aryl group, starting from phenolic Mannich bases and pyridinium ylides, has been developed. The mechanism of the reaction is believed to involve the formation of the o-quinone methide intermediate, Michael-type addition of the ylide to the o-quinone methide, followed by intramolecular nucleophilic substitution.