N-methyl-N-phenyl-1H-indole-2-carboxamide | 62048-32-2

• 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: N-methyl-N-phenyl-1H-indole-2-carboxamide
• CAS: 62048-32-2
• 化学式: C₁₆H₁₄N₂O
• 分子量: 250.3
• InChiKey: MIHVSSWKZWMTEP-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C(Solv: ethanol (64-17-5))
• 沸点：
  460.0±27.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-methyl-N-phenyl-1H-indole-2-carboxamide 在 copper diacetate 、 palladium diacetate 、 三甲基乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以91%的产率得到5-methyl-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one
  参考文献：
  名称：

  Palladium-Catalyzed Dual C(sp²)–H Functionalization of Indole-2-carboxamides Involving a 1,2-Acyl Migration: A Synthesis of Indolo[3,2-c]quinolinones

  摘要：

  A novel Pd/Cu catalytic system to construct indolo[3,2-c]quinolinones has been developed starting from indole-2-carboxamides, Substrates were transformed into indolo[3,2-c]quinolinones through dual C(sp(2))-H functionalization of the indole moiety and arene, in which a carbonyl 1,2-migration was involved. The corresponding products were obtained in moderate to excellent yields with a wide substrate scope.

  DOI：

  10.1021/acs.orglett.8b02419
• 作为产物：
  描述：

  N-methyl-N-phenyl-2-(5-ethylthioindole) carboxamide 在 三氯化铝 、 乙硫醇 作用下， 反应 12.0h， 以65%的产率得到N-methyl-N-phenyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  Functionalisation of the alkoxy group of alkyl aryl ethers. Demethylation, alkylthiolation and reduction of 5-methoxyindoles

  摘要：

  In the presence of AlX(3)-RSH three kinds of reactions may take place with 5-methoxy indoles : demethylation, alkylthiolation and reduction. The two latter reactions have never been observed to the present, with such reagents. Considerable improvement in the selective demethylation was found when PhCH(2)SH replaced EtSH previously used in such transformations. Factors leading to selective alkylthiolations or reductions are shown and mechanisms are proposed to explain these new reactions.

  DOI：

  10.1016/s0040-4020(01)89350-9

文献信息

• Synthesis of Indolo[2,3-<i>c</i>]quinolin-6(7<i>H</i>)-ones and Antimalarial Isoneocryptolepine. Computational Study on the Pd-Catalyzed Intramolecular C–H Arylation
  作者：Tímea Szabó、Marcell Papp、Dóra Rita Németh、András Dancsó、Balázs Volk、Mátyás Milen

  DOI：10.1021/acs.joc.0c01832

  日期：2021.1.1

  The synthesis of variously substituted indolo[2,3-c]quinolin-6(7H)-ones was developed via Pd-catalyzed intramolecular C–H arylation. This method highlights a strategy for preparing indoloquinoline precursors bearing versatile functional groups and provides a new approach for the synthesis of antimalarial isoneocryptolepine analogues. The plausible ring closure mechanism was examined with quantum chemical

  通过Pd催化的分子内C–H芳基化反应，开发了各种取代的吲哚[2,3 - c ]喹啉-6（7 H）-ones的合成。该方法突出了制备带有多功能官能团的吲哚喹啉前体的策略，并为合成抗疟异异烯油菜碱类似物提供了新方法。通过量子化学计算研究了可能的闭环机理，推测是三角双锥体协同的金属化-去质子化过渡态。
• Copper-Catalyzed Oxidative Dearomatization/Spirocyclization of Indole-2-Carboxamides: Synthesis of 2-Spiro-pseudoindoxyls
  作者：Lingkai Kong、Mengdan Wang、Fangfang Zhang、Murong Xu、Yanzhong Li

  DOI：10.1021/acs.orglett.6b03131

  日期：2016.12.2

  A copper-catalyzed oxidative dearomatization/spirocyclization of indole-2-carboxamides using tert-butyl hydroperoxide (TBHP) as the oxidant has been developed that provides rapid and efficient access to C2-spiro-pseudoindoxyls. Two of the sp2 C–H bonds are functionalized during the reaction process, and the reaction likely proceeds via the formation of a highly reactive 3H-indol-3-one intermediate

  已经开发出使用叔丁基氢过氧化物（TBHP）作为氧化剂的铜催化的吲哚-2-羧酰胺的氧化脱芳香化/螺环化，其提供了快速和有效地获得C 2-螺-伪吲哚酚的途径。sp 2 C–H键中的两个在反应过程中被官能化，反应可能通过形成高反应性的3 H-吲哚-3-一个中间体进行，然后通过芳基的N-芳基环进行亲电取代。酰胺部分。
• Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B
  作者：Giuseppe La Regina、Romano Silvestri、Valerio Gatti、Antonio Lavecchia、Ettore Novellino、Olivia Befani、Paola Turini、Enzo Agostinelli

  DOI：10.1016/j.bmc.2008.09.072

  日期：2008.11

  New monoamine oxidase inhibitors were synthesized as indole analogues of a previously reported pyrrole series. Several compounds were potent MAO-A (12, 17, 19-22, 31, 36, and 37) or MAO-B (14, 20, 24, 38, 44, and 46) inhibitors, and had K(i) values in the nanomolar concentration range. In particular, 22 (K(i)=0.00092 microM, and SI=68,478) was exceptionally potent and selective as MAO-A inhibitor.

  合成了新的单胺氧化酶抑制剂，作为先前报道的吡咯系列的吲哚类似物。几种化合物是有效的MAO-A（12、17、19-22、31、36和37）或MAO-B（14、20、24、38、44和46）抑制剂，具有K（i）值在纳摩尔浓度范围内。特别地，22（K（i）= 0.00092 microM，SI = 68,478）作为MAO-A抑制剂异常有效且具有选择性。在分子建模研究中，化合物22、24、44和46将吲哚环置于MAO-A的芳香腔中，并与Tyr407，Tyr444和FAD辅因子建立了pi-pi堆积相互作用。但是，只有化合物22能够与FAD形成氢键，这一发现与其有效的抗MAO-A活性相符。相反，在MD模拟过程中22 / MAOB复合物高度不稳定。
• Preparation of indole-2-carboxamides by palladium-catalysed carbonylation
  作者：John M. Herbert、Alan H. McNeill

  DOI：10.1016/s0040-4039(98)00215-9

  日期：1998.4

  Palladium-mediated carbonylation of a 2-iodoindole in the presence of an amine provides an efficient method for the preparation of indole-2-carboxamides. The process is clean and rapid, and appears to be general where the amine component is sufficiently non-volatile.

  在胺存在下钯介导的2-碘吲哚的羰基化为制备吲哚-2-羧酰胺提供了一种有效的方法。该方法干净，快速，并且在胺组分足够不挥发的情况下似乎很普遍。
• Chemoselective N–H or C-2 Arylation of Indole-2-carboxamides: Controllable Synthesis of Indolo[1,2-<i>a</i>]quinoxalin-6-ones and 2,3′-Spirobi[indolin]-2′-ones
  作者：Lingkai Kong、Yue Sun、Zhong Zheng、Rong Tang、Mengdan Wang、Yanzhong Li

  DOI：10.1021/acs.orglett.8b02197

  日期：2018.9.7

  chemoselective N–H or C-2 arylation for the synthesis of indolo[1,2-a]quinoxalin-6-ones and 2,3′-spirobi[indolin]-2′-ones starting from indole-2-carboxamides were developed. When reactions were carried out using ZnI2 as catalyst and Ag2CO3 as oxidant, indolo[1,2-a]quinoxalin-6-ones were synthesized in up to 86% yields via intramolecular N–H/C–H coupling, whereas the dearomative cyclization reactions were realized

  涉及化学选择性NH或C-2芳基化反应的新方法，从吲哚2开始合成吲哚并[1,2 - a ]喹喔啉-6-和2,3'-螺双[吲哚啉] -2'-。 -羧酰胺被开发出来。当使用ZnI 2作为催化剂和Ag 2 CO 3作为氧化剂进行反应时，通过分子内N–H / C–H偶联，吲哚[1,2 - a ]喹喔啉-6-一的合成产率高达86％，而脱芳香环化反应是在TfOH存在下实现的，通过C–H官能化或Fridel–Crafts烷基化反应导致吲哚的C-2芳基化，得到2,3'-spirbibi [indolin] -2'-ones。中等至极好的产量。