Methyl 8-hydroxy-2-oxo-2H-cycloheptafuran-3-carboxylate | 134919-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环七呋喃
• 英文名称: Methyl 8-hydroxy-2-oxo-2H-cycloheptafuran-3-carboxylate
• 英文别名: methyl 8-hydroxy-2-oxocyclohepta[b]furan-3-carboxylate
• CAS: 134919-69-0
• 化学式: C₁₁H₈O₅
• 分子量: 220.182
• InChiKey: ZRHKBOUHOWRKDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.74
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Methyl 8-hydroxy-2-oxo-2H-cycloheptafuran-3-carboxylate 在 sodium hydroxide 、 硫酸 、 sodium methylate 、 silver nitrate 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 3.5h， 生成 3-Cyano-2-diazo-4-oxo-2,4-dihydro-azulene-1-carboxylic acid methyl ester
  参考文献：
  名称：

  Formation and structure of 2-diazo-2,4-azulenequinone derivatives

  摘要：

  The diazotization of methyl (and ethyl) 2-amino-3-cyano-4-methoxy(and ethoxy)azulene-1-carboxylate (1-4) was examined to determine whether the products are 2-diazo-2,4-azulenequinone derivatives (B) or azulene-2-diazonium-1-carboxylate derivatives (C). Since diazotization of 1 and 2 gave the same diazo compound 5 and diazotization of both 3 and 4-gave diazo compound 6, the diazo compounds are deduced to not be azulene-2-diazonium-1-carboxylate derivatives (7 and 8), but rather to be 2-diazo-2,4-azulenequinone derivatives (5 and 6). The diazo carbons of both 5 and 6 show C-13 NMR signals at delta 66.3, and their carbonyl carbons resonate at 6 181.1, in good agreement with a 2-diazo-2,4-azulenequinone structure. The structures of diazo compounds 24 and 25, which we have previously reported,(1) are reexamined on the basis of the analysis of their C-13 NMR spectra. The contribution of a quinoid structure and a diazoazulenolate structure to 5, 6, 24, and 25 is discussed by comparison of their C-13 NMR spectral data with those of 4-diazo-2,5-cyclohexadien-1-one derivatives. It is concluded that the contribution of the quinoid structure is larger than that of the diazoazulenolate structure.

  DOI：

  10.1021/jo00123a031
• 作为产物：
  描述：

  3-(甲氧羰基)-2H-环庚[b]呋喃-2-酮 在 盐酸 作用下， 以97%的产率得到Methyl 8-hydroxy-2-oxo-2H-cycloheptafuran-3-carboxylate
  参考文献：
  名称：

  Formation and structure of 2-diazo-2,4-azulenequinone derivatives

  摘要：

  The diazotization of methyl (and ethyl) 2-amino-3-cyano-4-methoxy(and ethoxy)azulene-1-carboxylate (1-4) was examined to determine whether the products are 2-diazo-2,4-azulenequinone derivatives (B) or azulene-2-diazonium-1-carboxylate derivatives (C). Since diazotization of 1 and 2 gave the same diazo compound 5 and diazotization of both 3 and 4-gave diazo compound 6, the diazo compounds are deduced to not be azulene-2-diazonium-1-carboxylate derivatives (7 and 8), but rather to be 2-diazo-2,4-azulenequinone derivatives (5 and 6). The diazo carbons of both 5 and 6 show C-13 NMR signals at delta 66.3, and their carbonyl carbons resonate at 6 181.1, in good agreement with a 2-diazo-2,4-azulenequinone structure. The structures of diazo compounds 24 and 25, which we have previously reported,(1) are reexamined on the basis of the analysis of their C-13 NMR spectra. The contribution of a quinoid structure and a diazoazulenolate structure to 5, 6, 24, and 25 is discussed by comparison of their C-13 NMR spectral data with those of 4-diazo-2,5-cyclohexadien-1-one derivatives. It is concluded that the contribution of the quinoid structure is larger than that of the diazoazulenolate structure.

  DOI：

  10.1021/jo00123a031

文献信息

• Synthesis and Analysis of Positive Inotropic Effects of 3-Substituted-2H-cyclohepta(b)furan-2-one Derivatives.
  作者：Masayuki YOKOTA、Takashi YANAGISAWA、Kazuhiro KOSAKAI、Shuichi WAKABAYASHI、Tsuyoshi TOMIYAMA、Masafumi YASUNAMI

  DOI：10.1248/cpb.42.865

  日期：——

  Several 3-substituted-2H-cyclohepta[b]furan-2-one derivatives were prepared and tested in vitro for positive inotropic character. Introduction of an isopropyl group at the 5-position of compound 8a caused an increase of PIC50 (negative logarithm of the dosage which increases the contractile force by 50%) from 4.48 to 5.10. Among the 5-isopropyl-8-alkoxy compounds, the isopropoxy compound 12f had the most potent activity with a PIC50 value of 5.99. Conversion of the ester group at the 3-position to a methylene group and of the alkoxy group at the 8-position to a substituted amino group caused a decrease in activity. The most active compound, 12f, was also found to have a weaker heart rate (HR)-increasing effect compared to milrinone and amrinone.

  合成了几种3-取代的-2H-环庚[b]呋喃-2-酮衍生物，并在体外测试了它们的正性肌力特性。在化合物8a的5-位引入异丙基，使得PIC50值（增加收缩力50%的剂量的负对数）从4.48增加到5.10。在5-异丙基-8-烷氧基化合物中，异丙氧基化合物12f具有最强的活性，PIC50值为5.99。将3-位的酯基转换为亚甲基，将8-位的烷氧基转换为取代氨基，会导致活性降低。最活跃的化合物12f，与米力农和氨力农相比，对心率（HR）增加的影响较弱。
• Nozoe, Tetsuo; Wakabayashi, Hidetsugu; Shindo, Kimio, Heterocycles, 1991, vol. 32, # 2, p. 213 - 220
  作者：Nozoe, Tetsuo、Wakabayashi, Hidetsugu、Shindo, Kimio、Ishikawa, Sumio、Wu, Chi-Phi、Yang, Paw-Wang

  DOI：——

  日期：——
• Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors
  作者：Chih-Hung Chen、On Lee、Chung-Niang Yao、Meng-Yun Chuang、Yow-Lone Chang、May-Hua Chang、Yen-Fang Wen、Wan-Hsu Yang、Ching-Huai Ko、Nien-Tzu Chou、Mai-Wei Lin、Chin-Pen Lai、Chung-Yuan Sun、Ling-mei Wang、Yen-Chun Chen、Tzong-Hsiung Hseu、Chia-Ni Chang、Hui-Chun Hsu、Hui-Chi Lin、Yu-Li Chang、Ying-Chu Shih、Shuen-Hsiang Chou、Yi-Ling Hsu、Hsiang-Wen Tseng、Chih-Peng Liu、Chia-Mu Tu、Tsan-Lin Hu、Yuan-Jang Tsai、Ting-Shou Chen、Chih-Lung Lin、Shu-Jiau Chiou、Chung-Cheng Liu、Chrong-Shiong Hwang

  DOI：10.1016/j.bmcl.2010.08.025

  日期：2010.10

  A series of azulene-based derivatives were synthesized as potent inhibitors for receptor tyrosine kinases such as FMS-like tyrosine kinase 3 (FLT-3). Systematic side chain modification of prototype 1a was carried out through SAR studies. Analogue 22 was identified from this series and found to be one of the most potent FLT-3 inhibitors, with good pharmaceutical properties, superior efficacy, and tolerability in a tumor xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.
• Yokota Masayuki, Yanagisawa Takashi, Kosakai Kazuhiro, Wakabayashi Shuich+, Chem. and Pharm. Bull, 42 (1994) N 4, S 865-871
  作者：Yokota Masayuki, Yanagisawa Takashi, Kosakai Kazuhiro, Wakabayashi Shuich+

  DOI：——

  日期：——
• Formation and structure of 2-diazo-2,4-azulenequinone derivatives
  作者：Tetsuo Nozoe、Toyonobu Asao、Masafumi Yasunami、Hisamitu Wakui、Toshio Suzuki、Masayoshi Ando

  DOI：10.1021/jo00123a031

  日期：1995.9

  The diazotization of methyl (and ethyl) 2-amino-3-cyano-4-methoxy(and ethoxy)azulene-1-carboxylate (1-4) was examined to determine whether the products are 2-diazo-2,4-azulenequinone derivatives (B) or azulene-2-diazonium-1-carboxylate derivatives (C). Since diazotization of 1 and 2 gave the same diazo compound 5 and diazotization of both 3 and 4-gave diazo compound 6, the diazo compounds are deduced to not be azulene-2-diazonium-1-carboxylate derivatives (7 and 8), but rather to be 2-diazo-2,4-azulenequinone derivatives (5 and 6). The diazo carbons of both 5 and 6 show C-13 NMR signals at delta 66.3, and their carbonyl carbons resonate at 6 181.1, in good agreement with a 2-diazo-2,4-azulenequinone structure. The structures of diazo compounds 24 and 25, which we have previously reported,(1) are reexamined on the basis of the analysis of their C-13 NMR spectra. The contribution of a quinoid structure and a diazoazulenolate structure to 5, 6, 24, and 25 is discussed by comparison of their C-13 NMR spectral data with those of 4-diazo-2,5-cyclohexadien-1-one derivatives. It is concluded that the contribution of the quinoid structure is larger than that of the diazoazulenolate structure.

表征谱图