4-(3,4-dimethoxyphenethyl)-7-(tetrahydro-2H-pyran-2-yl)-2H-pyridazino[4,5-b][1,4]oxazine-3,8(4H,7H)-dione | 645405-25-0

• 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: 4-(3,4-dimethoxyphenethyl)-7-(tetrahydro-2H-pyran-2-yl)-2H-pyridazino[4,5-b][1,4]oxazine-3,8(4H,7H)-dione
• 英文别名: 4-[2-(3,4-Dimethoxyphenyl)ethyl]-7-(oxan-2-yl)pyridazino[4,5-b][1,4]oxazine-3,8-dione
• CAS: 645405-25-0
• 化学式: C₂₁H₂₅N₃O₆
• 分子量: 415.446
• InChiKey: LLHLCVHYRCTSEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3,4-dimethoxyphenethyl)-7-(tetrahydro-2H-pyran-2-yl)-2H-pyridazino[4,5-b][1,4]oxazine-3,8(4H,7H)-dione 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 4-[2-(3,4-Dimethoxyphenyl)ethyl]-3-hydroxy-7-(oxan-2-yl)-2,3-dihydropyridazino[4,5-b][1,4]oxazin-8-one
  参考文献：
  名称：

  Synthetic Studies on Isoquinoline Derivatives with Multidrug Resistance (MDR) Modulating Activity

  摘要：

  Tetrahydropyridazino-1,4-oxazinoisoquinoline derivatives with multidrug resistance (MDR) modulating activity were designed and synthesized. A key step for cyclization of 1,4-oxazine ring was developed using K2CO3 and CH3CN in one-pot. Among prepared compounds, 2-(4-fluorobenzyl)-9,10-dimethoxy-12-methyl-6,7,11b,12-tetrahydropyridazino[4',5',5,6][1,4]oxazine[3,4,-a]isoquinolin-1(2H)-one (If) exhibited significant MDR reversing activity and low toxicity, which might be as potential MDR agent.

  DOI：

  10.3987/com-03-9918
• 作为产物：
  描述：

  4,5-二氯-2-(四氢-吡喃-2-基)-2H-吡嗪-3-酮 在 氢氧化钾 、 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 66.0h， 生成 4-(3,4-dimethoxyphenethyl)-7-(tetrahydro-2H-pyran-2-yl)-2H-pyridazino[4,5-b][1,4]oxazine-3,8(4H,7H)-dione
  参考文献：
  名称：

  Novel formation of 1,3-oxazepine heterocycles via palladium-catalyzed intramolecular coupling reaction

  摘要：

  The oxazepine ring systems containing pyridazinone moiety were constructed via palladium-catalyzed intramolecular coupling reaction. The best conditions for this reaction were Pd(OAc)(2) as a palladium source, 1,1'-bis(diphenylphosphino)-ferrocene (DPPF) as the ligand, and K2CO3 as base at 80 degrees C in toluene. The products have potential applications as biological and medicinal relevant compounds. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.07.009

文献信息

• Novel synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones☆
  作者：Su-Dong Cho、Sang-Yong Song、Yong-Dae Park、Jeum-Jong Kim、Woo-Hong Joo、Motoo Shiro、J.R. Falck、Dong-Soo Shin、Yong-Jin Yoon

  DOI：10.1016/j.tetlet.2003.09.216

  日期：2003.12.8

  A novel and effective synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones via Smiles rearrangement is presented. Treatment of N-substituted 2-chloro(or hydroxy)acetamide, 2-tetrahydropyranyl-4-chloro-5-hydroxy(or chloro)pyridazin-3-one and cesium carbonate in refluxing acetonitrile was afforded the corresponding pyridazino[4,5-b][1,4]oxazin-3,8-diones in excellent yield.

  提出了一种通过Smiles重排合成新颖有效的哒嗪并[4,5- b ] [1,4]恶嗪-3,8-二酮的方法。在回流的乙腈中处理N-取代的2-氯（或羟基）乙酰胺，2-四氢吡喃基-4-氯-5-羟基（或氯）哒嗪-3-酮和碳酸铯，得到相应的哒嗪[4,5-]。b ] [1,4]恶嗪-3,8-二酮，收率高。
• One‐Pot Synthesis of Pyridazino[1,4]oxazin‐3‐ones
  作者：Chen Ma、Su‐Dong Cho、J. R. Falck、Dong‐Soo Shin

  DOI：10.1081/scc-120030689

  日期：2004.12.31

  Pyridazino[1,4] oxazin-3-ones were conveniently prepared in a one-pot condensation of N-substituted 2-chloroacetamides with various 5-chloro-pyridazin-6-ones via rearrangement of a spiro-aminoketal intermediate.
• An efficient synthesis of [1,4]pyridazinooxazine[3,4-a]tetrahydro isoquinolines
  作者：Su-Dong Cho、Yong-Dae Park、Jeum-Jong Kim、Woo-Hong Joo、Motoo Shiro、Lothar Esser、J.R Falck、Chuljin Ahn、Dong-Soo Shin、Yong-Jin Yoon

  DOI：10.1016/j.tet.2004.03.011

  日期：2004.4

  A series of fused isoquinoline-pyridazinooxazine chimera were prepared in good overall yield from phenethylamide I and 4,5-dichloropyridazin-3-one 2 via Smiles rearrangement and Pictet-Spengler cyclization. (C) 2004 Elsevier Ltd. All rights reserved.
• Novel formation of 1,3-oxazepine heterocycles via palladium-catalyzed intramolecular coupling reaction
  作者：Chen Ma、Shao-Jie Liu、Liang Xin、J.R. Falck、Dong-Soo Shin

  DOI：10.1016/j.tet.2006.07.009

  日期：2006.9

  The oxazepine ring systems containing pyridazinone moiety were constructed via palladium-catalyzed intramolecular coupling reaction. The best conditions for this reaction were Pd(OAc)(2) as a palladium source, 1,1'-bis(diphenylphosphino)-ferrocene (DPPF) as the ligand, and K2CO3 as base at 80 degrees C in toluene. The products have potential applications as biological and medicinal relevant compounds. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthetic Studies on Isoquinoline Derivatives with Multidrug Resistance (MDR) Modulating Activity
  作者：Chen Ma、Su-Dong Cho、J. R. Falck、Dong-Soo Shin

  DOI：10.3987/com-03-9918

  日期：——

  Tetrahydropyridazino-1,4-oxazinoisoquinoline derivatives with multidrug resistance (MDR) modulating activity were designed and synthesized. A key step for cyclization of 1,4-oxazine ring was developed using K2CO3 and CH3CN in one-pot. Among prepared compounds, 2-(4-fluorobenzyl)-9,10-dimethoxy-12-methyl-6,7,11b,12-tetrahydropyridazino[4',5',5,6][1,4]oxazine[3,4,-a]isoquinolin-1(2H)-one (If) exhibited significant MDR reversing activity and low toxicity, which might be as potential MDR agent.