methyl 5-hydroxyquinoline-6-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 5-hydroxyquinoline-6-carboxylate
• 英文别名: Methyl 5-hydroxyquinoline-6-carboxylate
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: MXMXNUCGQSHTNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯烟酸甲酯 、 3-丁烯酸甲酯 在 二(三叔丁基膦)钯 、 N-甲基二环己基胺 、 potassium tert-butylate 作用下， 以 1,4-二氧六环 、 四氢呋喃 为溶剂， 反应 4.0h， 以16%的产率得到methyl 5-hydroxyquinoline-6-carboxylate
  参考文献：
  名称：

  Efficient Access to Methyl-1-hydroxy-2-naphthoates and Heterocyclic Analogues

  摘要：

  We report the synthesis of methyl-1-hydroxy-2-naphthoate derivatives and heterocyclic analogues using a two-step approach. This short route employs a Heck coupling of a 2-halo-benzoate with methyl 3-butenoate followed by a Dieckmann cyclization, yielding the 1-hydroxynaphthalene-2-carboxylic acid derivatives in the multigram scale.

  DOI：

  10.1021/acs.oprd.5b00280

文献信息

• Synthesis and Structure-Activity Relationship of 3-Substituted Benzamide, Benzo(b)furan-7-carboxamide, 2,3-Dihydrobenzo(b)furan-7-carboxamide, and Indole-5-carboxamide Derivatives as Selective Serotonin 5-HT4 Receptor Agonits.
  作者：Takuji KAKIGAMI、Toshinao USUI、Katsura TSUKAMOTO、Tadashi KATAOKA

  DOI：10.1248/cpb.46.42

  日期：——

  The title compounds (6-9) were prepared and evaluated for serotonin 5-HT4 agonistic activity in in vitro tests. Introducing a propyl or allyl group at the 3-position of benzamide caused only a slight enhancement of agonistic activity. Construction of the benzo[b]furan skeleton and 2, 3-dihydrobenzo[b]furan skeleton caused a significant enhancement of the activity. 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2-methylbenzo[b]furan-7-carboxamide (7b) hemifumarate was as potent as cisapride. 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2, 3-dihydro-2-methylbenzo[b]furan-7-carboxamide (8a) hemifumarate, 4-amino-N-[2-(1-azabicyclo-[3.3.0]octan-5-yl)ethyl]-5-chloro-2, 3-dihydro-2-ethylbenzo[b]furan-7-carboxamide (8c) hemifumarate, and 4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2, 3-dihydro-2, 3-dimethylbenzo[b]furan-7-carboxamide (8d) hemifumarate were potent than cisapride. Furthermore, 8a hemifumarate was free from dopamine D1, D2, serotonin 5-HT1, 5-HT2 and muscarine M1, M2 receptor binding activity in the in vitro tests. On the other hand, construction of the indole skeleton caused a remarkable decrease in activity.

  标题化合物（6-9）已被合成并在体外测试中评估其对血清素5-HT4的激动活性。在苯酰胺的3位引入丙基或烯丙基仅导致激动活性的轻微增强。而构建苯并[b]呱骨架和2,3-二氢苯并[b]呱骨架则显著增强了活性。4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2-甲基苯并[b]呱-7-羧酰胺（7b）半富马酸盐的效力与西沙必利相当。4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2-甲基苯并[b]呱-7-羧酰胺（8a）半富马酸盐，4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2-乙基苯并[b]呱-7-羧酰胺（8c）半富马酸盐，以及4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2,3-二甲基苯并[b]呱-7-羧酰胺（8d）半富马酸盐的效力均优于西沙必利。此外，8a半富马酸盐在体外测试中未表现出对多巴胺D1、D2、血清素5-HT1、5-HT2及毒蕈碱M1、M2受体的结合活性。另一方面，构建吲哚骨架则导致活性显著降低。
• Efficient Access to Methyl-1-hydroxy-2-naphthoates and Heterocyclic Analogues
  作者：Michael A. L. Podeschwa、Kai Rossen

  DOI：10.1021/acs.oprd.5b00280

  日期：2015.12.18

  We report the synthesis of methyl-1-hydroxy-2-naphthoate derivatives and heterocyclic analogues using a two-step approach. This short route employs a Heck coupling of a 2-halo-benzoate with methyl 3-butenoate followed by a Dieckmann cyclization, yielding the 1-hydroxynaphthalene-2-carboxylic acid derivatives in the multigram scale.