2-甲基-7-硝基-1,2-二氢异喹啉-3(4H)-酮 | 1199813-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 2-甲基-7-硝基-1,2-二氢异喹啉-3(4H)-酮
• 英文名称: 2-methyl-7-nitro-1,2-dihydroisoquinolin-3(4H)-one
• 英文别名: 7-nitro-2-methyl-1,4-dihydro-2H-isoquinolin-3-one；2-Methyl-7-nitro-1,2-dihydroisoquinolin-3(4H)-one；2-methyl-7-nitro-1,4-dihydroisoquinolin-3-one
• CAS: 1199813-82-5
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: OAZNUWVXHRYGEN-UHFFFAOYSA-N

物化性质

• 沸点：
  406.8±45.0 °C(Predicted)
• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933790090

反应信息

• 作为反应物：
  描述：

  2-甲基-7-硝基-1,2-二氢异喹啉-3(4H)-酮 在 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 氢气 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 乙酸乙酯 、 丙酮 为溶剂， 35.0~80.0 ℃ 、137.9 kPa 条件下， 反应 10.17h， 生成 4-(4-(benzothiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)morpholine maleate
  参考文献：
  名称：

  Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780

  摘要：

  Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton's reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.

  DOI：

  10.1021/op3000064
• 作为产物：
  描述：

  2-(4-硝基苯基)乙酰氯 在 Eaton’s reagent 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-甲基-7-硝基-1,2-二氢异喹啉-3(4H)-酮
  参考文献：
  名称：

  Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780

  摘要：

  Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton's reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.

  DOI：

  10.1021/op3000064

文献信息

• 2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase
  作者：Christopher J. Matheson、Christopher R. Coxon、Richard Bayliss、Kathy Boxall、Benoit Carbain、Andrew M. Fry、Ian R. Hardcastle、Suzannah J. Harnor、Corine Mas-Droux、David R. Newell、Mark W. Richards、Mangaleswaran Sivaprakasam、David Turner、Roger J. Griffin、Bernard T. Golding、Céline Cano

  DOI：10.1039/d0md00074d

  日期：——

  Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal

  人们对与疾病状态有关的酶的共价抑制剂重新产生了兴趣，从而提供了几种针对与癌症相关的蛋白激酶的药物。我们现在报告了 6-乙炔基嘌呤的设计、合成和生物学评价，6-乙炔基嘌呤通过捕获靠近该蛋白激酶催化结构域的半胱氨酸残基 (Cys22) 来充当 Nek2 的共价抑制剂。对与 Nek2 复合的非共价抑制剂 3-((6-环己基甲氧基-7 H-嘌呤-2-基)氨基)苯甲酰胺的晶体结构的检查表明，用乙炔基取代烷氧基放置了炔烃的末端接近Cys22并且处于与迈克尔加成的立体电子学要求兼容的位置。制备了一系列 6-乙炔基嘌呤并建立了抑制 Nek2 的结构活性关系 (SAR)。 6-乙炔基-N-苯基-7 H-嘌呤-2-胺 [IC 50 0.15 μM (Nek2)] 和 4-((6-乙炔基-7 H-嘌呤-2-基)氨基)苯磺酰胺 (IC 50 0.14)选择 Nek2 的抑制模式来确定 Nek2 的抑制模式，该抑制模式具有时间依赖性，不能通过添加
• Process Development and Pilot-Scale Synthesis of New Cyclization Conditions of Substituted Phenylacetamides to Tetrahydroisoquinoline-2-ones Using Eaton’s Reagent
  作者：Luckner G. Ulysse、Qiang Yang、Mark D. McLaws、Daniel K. Keefe、Peter R. Guzzo、Brian P. Haney

  DOI：10.1021/op9002533

  日期：2010.1.15

  Tetra hydroisoquinoline is a ubiquitous structural framework presented in numerous pharmacologically relevant molecules. Although accessible by the Pictet-Spengler cyclization, conditions commonly used for such cyclizations are often difficult to implement on scale. Herein, we report the development of a scaleable approach utilizing Eaton's reagent for the cyclization of substituted phenylacetamide analogues to tetrahydroisoquinoline-2-one. The development, optimization, and safety hazard evaluations, which outline the benefits and ease of workup of this new process, are discussed.
• Preparation of Tetrahydroisoquinoline-3-ones via Cyclization of Phenyl Acetamides Using Eaton's Reagent
  作者：Yang, Qiang、Ulysse Jr., Luckner G.、McLaws, Mark、Keefe, Daniel K.、Guzzo, Peter、Haney, Brian P.

  DOI：10.15227/orgsyn.089.0044

  日期：——
• Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780
  作者：Qiang Yang、Luckner G. Ulysse、Mark D. McLaws、Daniel K. Keefe、Brian P. Haney、Congxiang Zha、Peter R. Guzzo、Shuang Liu

  DOI：10.1021/op3000064

  日期：2012.3.16

  Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton's reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.