1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine | 817160-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
• 英文别名: 3-methoxy-1-(2-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine；3-methoxy-1-(2-nitrophenyl)sulfonyl-3,5-dihydro-2H-4,1-benzoxazepine
• CAS: 817160-16-0
• 化学式: C₁₆H₁₆N₂O₆S
• 分子量: 364.379
• InChiKey: CFZBQZSMQIWQRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine 在 三甲基氯硅烷 、 氘代二甲亚砜 、 水 、 四氯化锡 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 重水 、 乙腈 为溶剂， 反应 168000.0h， 生成 7-[1-(2-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-1,7-dihydropurin-6-one
  参考文献：
  名称：

  带有硝基苯磺酰基的（RS）-6-氯-7-或9-（1,2,3,5-四氢-4,1-苯并恶唑啉-3-基）-7 H-或9 H-嘌呤的合成与反应性氮原子上的基团

  摘要：

  的Ô，Ô -acetalic化合物（RS）-3-甲氧基-1 - [（2） -或（4）-nitrobenzenesulfonyl）] - 1,2,3,5-四氢-4,1-苯并氧氮杂已经研究了在路易斯酸介导的与6-氯嘌呤的缩合反应。6-氯嘌呤在环状产物中导致N -7“氨基键，而在非环状产物中主要导致N -9”氨基键。在6的氯原子的取代“当环被烷基化的嘌呤部分的位置是更可行Ñ比-7” Ñ-9”。在室温下，在溶剂介导的过程中，在氘代二甲基亚砜中与痕量水进行羟基交换。与强亲核试剂（例如，苯硫酚）的交换不需要进一步激活。

  DOI：

  10.1016/j.tet.2007.03.155
• 作为产物：
  描述：

  N-[2-(tert-butyldimethylsilanyloxymethyl)phenyl]-2-nitrobenzenesulfonamide 在 偶氮二甲酸二异丙酯 、 三氟化硼乙醚 、 四丁基氟化铵 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 22.0h， 生成 1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
  参考文献：
  名称：

  Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells

  摘要：

  Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5-tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new 0,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.09.072

文献信息

• Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine <i>O</i>,<i>O</i>-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom
  作者：Mónica Díaz-Gavilán、José A. Gómez-Vidal、Antonio Entrena、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1021/jo052167m

  日期：2006.2.1

  derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 °C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1‘ ‘ position, while the attachment of the uracil fragment is through N-3‘ ‘

  （RS）-1-（2-硝基苯磺酰基）-和（RS）-1-（4-硝基苯磺酰基）-3-甲氧基-1,2,3,5-四氢-4,1-苯并x庚因是比1-更好的底物酰基-3-甲氧基-1,2,3,5-四氢-4,1-苯并x并庚因衍生物，在路易斯酸介导的与嘧啶碱的缩合反应中生成O，N-乙缩醛。乙腈，氯化锡，50°C和高于48小时的反应时间是此类缩合反应的最佳条件。在这些条件下，5-氟尿嘧啶优选通过其N -1''位置连接至氨基碳，而尿嘧啶片段的连接通过N -3''或N-1''分别为环状或非环状产物。分析和讨论了影响反应过程的原因。所述的检查1核磁共振光谱揭示了单一形式的存在下，仲胺11和两种构象异构体的叔磺酰胺7a中，b，图9a，b，和图10b以及用于酰胺7D和13，具有以下的分布：7a，59/41; 7b，53/47；9a，52/48；9b，59/41; 10b，56/44；7d，50/50; 13，80/20。随着温度的升高，7b的1
• New (RS)-benzoxazepin-purines with antitumour activity: The chiral switch from (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine
  作者：Luisa C. López-Cara、Ana Conejo-García、Juan A. Marchal、Giuseppe Macchione、Olga Cruz-López、Houria Boulaiz、María A. García、Fernando Rodríguez-Serrano、Alberto Ramírez、Carlos Cativiela、Ana I. Jiménez、Juan M. García-Ruiz、Duane Choquesillo-Lazarte、Antonia Aránega、Joaquín M. Campos

  DOI：10.1016/j.ejmech.2010.11.011

  日期：2011.1

  Completing an SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines has been prepared under microwave-assisted conditions. Their antiproliferative activities on MCF-7 and MDA-MB-231 cancerous cell lines are presented, being the majority of the IC50 values below 1 mu M. The most active compound (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1- benzoxazepin-3-yl]-9H-purine (14) presents an IC50 of 0.166 mu M against the human cancerous cell line MDA-MB-231. Compound 14 was the most selective against the human breast adenocarcinoma MCF-7 and MDA-MB-231 cancer cell lines (Therapeutic Indexes, TIs = 5.1 and 11.0, respectively) in relation to the normal one MCF-10A. (RS)-14 was resolved into its enantiomers. Both enantiomers are equally potent, but more potent than the corresponding racemic mixture. (R)-14 induces apoptosis against MCF-7 up to 52.50% of cell population after 48 h, being more potent than the clinical-used drug paclitaxel (43%). (RS)-14 induces no acute toxicity in mice after two weeks of treatment. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells
  作者：Mónica Díaz-Gavilán、Fernando Rodríguez-Serrano、José A. Gómez-Vidal、Juan A. Marchal、Antonia Aránega、Miguel Á. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.tet.2004.09.072

  日期：2004.12

  Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5-tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new 0,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and reactivity of (RS)-6-chloro-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)-7H- or 9H-purines bearing a nitrobenzenesulfonyl group on the nitrogen atom
  作者：Mónica Díaz-Gavilán、Duane Choquesillo-Lazarte、Josefa M. González-Pérez、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.tet.2007.03.155

  日期：2007.6

  acid-mediated condensation with 6-chloropurine. 6-Chloropurine leads to the N-7″ aminalic bond in the cyclic products and mainly to the N-9″ aminalic bond in the acyclic ones. Substitution of the chlorine atom at the 6″ position of the purine moiety is more feasible when the ring is alkylated at N-7″ than at N-9″. Exchange with a hydroxyl group is performed with water traces in deuterated dimethylsulfoxide

  的Ô，Ô -acetalic化合物（RS）-3-甲氧基-1 - [（2） -或（4）-nitrobenzenesulfonyl）] - 1,2,3,5-四氢-4,1-苯并氧氮杂已经研究了在路易斯酸介导的与6-氯嘌呤的缩合反应。6-氯嘌呤在环状产物中导致N -7“氨基键，而在非环状产物中主要导致N -9”氨基键。在6的氯原子的取代“当环被烷基化的嘌呤部分的位置是更可行Ñ比-7” Ñ-9”。在室温下，在溶剂介导的过程中，在氘代二甲基亚砜中与痕量水进行羟基交换。与强亲核试剂（例如，苯硫酚）的交换不需要进一步激活。