4-methoxymethyl-1-naphthaldehyde | 739333-51-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-methoxymethyl-1-naphthaldehyde
• 英文别名: 4-methoxy-1-naphthaldehyde；4-(Methoxymethyl)naphthalene-1-carbaldehyde
• CAS: 739333-51-8
• 化学式: C₁₃H₁₂O₂
• 分子量: 200.237
• InChiKey: AKWZGCOZRFEOKK-UHFFFAOYSA-N

物化性质

• 沸点：
  345.4±17.0 °C(predicted)
• 密度：
  1.148±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methoxymethyl-1-naphthaldehyde 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 4-methoxymethyl-1-naphthylcarbinol
  参考文献：
  名称：

  钯催化的 3-芳基氧化吲哚的不对称苄基化反应

  摘要：

  在这里，我们报告了钯催化的不对称苄基烷基化，以 3-芳基羟吲哚作为前手性亲核试剂。与不对称烯丙基烷基化类似地进行，使用手性双膦配体对各种未保护的 3-芳基羟吲哚和苄基甲基碳酸酯以高产率和对映选择性发生不对称苄化。该方法代表在苄基和前手性亲核试剂之间形成新的不对称碳-碳键以生成季中心。

  DOI：

  10.1021/ja1079755
• 作为产物：
  描述：

  4-hydroxymethyl-1-naphthaldehyde 在 盐酸 、 硫酸 、 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 21.0h， 生成 4-methoxymethyl-1-naphthaldehyde
  参考文献：
  名称：

  Optimization of Alkylidene Hydrazide Based Human Glucagon Receptor Antagonists. Discovery of the Highly Potent and Orally Available 3-Cyano-4-hydroxybenzoic Acid [1-(2,3,5,6-Tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide

  摘要：

  Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-eyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure-metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylenelhydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, K-B = 760 pM) and of the isolated rat receptor IC50 = 430 pM, K-B = 380 pM). Glucagon-stimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (K-i = 14 nM). This compound was orally available in dogs (F-po = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.

  DOI：

  10.1021/jm0208572

文献信息

• Optimization of Alkylidene Hydrazide Based Human Glucagon Receptor Antagonists. Discovery of the Highly Potent and Orally Available 3-Cyano-4-hydroxybenzoic Acid [1-(2,3,5,6-Tetramethylbenzyl)-1<i>H</i>-indol-4-ylmethylene]hydrazide
  作者：Peter Madsen、Anthony Ling、Michael Plewe、Christian K. Sams、Lotte B. Knudsen、Ulla G. Sidelmann、Lars Ynddal、Christian L. Brand、Birgitte Andersen、Douglas Murphy、Min Teng、Larry Truesdale、Dan Kiel、John May、Atsuo Kuki、Shenghua Shi、Michael D. Johnson、Kimberly Ann Teston、Jun Feng、James Lakis、Kenna Anderes、Vlad Gregor、Jesper Lau

  DOI：10.1021/jm0208572

  日期：2002.12.1

  Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-eyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure-metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylenelhydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, K-B = 760 pM) and of the isolated rat receptor IC50 = 430 pM, K-B = 380 pM). Glucagon-stimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (K-i = 14 nM). This compound was orally available in dogs (F-po = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.
• Palladium-Catalyzed Asymmetric Benzylation of 3-Aryl Oxindoles
  作者：Barry M. Trost、Lara C. Czabaniuk

  DOI：10.1021/ja1079755

  日期：2010.11.10

  we report palladium-catalyzed asymmetric benzylic alkylation with 3-aryl oxindoles as prochiral nucleophiles. Proceeding analogously to asymmetric allylic alkylation, asymmetric benzylation occurs in high yield and enantioselectivity for a variety of unprotected 3-aryl oxindoles and benzylic methyl carbonates using chiral bisphosphine ligands. This methodology represents a novel asymmetric carbon-carbon

  在这里，我们报告了钯催化的不对称苄基烷基化，以 3-芳基羟吲哚作为前手性亲核试剂。与不对称烯丙基烷基化类似地进行，使用手性双膦配体对各种未保护的 3-芳基羟吲哚和苄基甲基碳酸酯以高产率和对映选择性发生不对称苄化。该方法代表在苄基和前手性亲核试剂之间形成新的不对称碳-碳键以生成季中心。