methyl 5-ethenyl-6-hydroxy-nicotinate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 5-ethenyl-6-hydroxy-nicotinate
• 英文别名: methyl 5-ethenyl-6-oxo-1H-pyridine-3-carboxylate
• 化学式: C₉H₉NO₃
• 分子量: 179.175
• InChiKey: FGFXRLQMPUMXBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 5-ethenyl-6-hydroxy-nicotinate 在 三氯氧磷 作用下， 反应 1.0h， 以1.45 g的产率得到methyl 6-chloro-5-ethenyl-nicotinate
  参考文献：
  名称：

  1,4-DISUBSTITUTED IMIDAZOLE DERIVATIVE

  摘要：

  本发明提供了一种公式（1'）的1,4-二取代咪唑衍生物，其中环Q1是可选取代的C6-10芳基等；R1和R2分别是氢原子等；W1是可选取代的C1-4烷基烯基；W2是—NR3aC(O)—，其中R3a是氢原子或C1-6烷基等；环Q2是5-到10-成员杂芳基等；W3是可选取代的C1-4烷基烯基等；n为1, 2, 3, 4或5；R4是独立的卤原子、可选取代的C1-6烷基等；R5是羟基等；以及其药理学上可接受的盐，对癌细胞的球形形成能力具有强大的抑制作用，并且作为口服抗肿瘤药剂是有用的。

  公开号：

  US20170166552A1
• 作为产物：
  描述：

  乙烯基硼酸二丁酯 、 5-碘-6-氧代-1H-吡啶-3-羧酸甲酯 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 以42%的产率得到methyl 5-ethenyl-6-hydroxy-nicotinate
  参考文献：
  名称：

  Enantio- and Regioselective Epoxidation of Olefinic Double Bonds in Quinolones, Pyridones, and Amides Catalyzed by a Ruthenium Porphyrin Catalyst with a Hydrogen Bonding Site

  摘要：

  An array of differently substituted 3-alkenylquinolones was synthesized, and the enantio- and regioselectivity of their Ru-catalyzed epoxidation were studied. A precursor ruthenium(II) complex with a chiral tricyclic gamma-lactam skeleton (octahydro-1H-4,7-methanoisoindol-1-one) was available by Sonogashira cross-coupling with a monobromo-substituted ruthenium(II) porphyrin. Enantioselective epoxidation reactions (60-83% yield, 85-98% ee) were achieved with this catalyst, and it was shown that the enantioselectivity depends critically on the presence of a two-point hydrogen bond interaction between the gamma-lactam site of the catalyst and the delta-lactam (quinolone) site of the substrate. DFT calculations support the hypothesis that the reaction occurs via a hydrogen-bound transition state, in which the 3-alkenylquinolone adopts an s-trans conformation. The calculations further revealed that this transition state is preferred over a competing s-cis transition state because it exerts less strain in the rigid backbone and because the hydrogen bond interaction is more stable. The catalyst loading required for complete conversion was low (<0.2 mol %), and turnover numbers exceeding 4000 were recorded. It was shown that there is little, if any, inhibition of the catalytic process by other quinolones, which could potentially compete with the binding site. A mechanistic model for the catalytic reaction is presented. In accordance with this model 3-alkenylpyridones reacted with similar enantioselectivities as the respective quinolones. The epoxidation products were unstable, however, and the enantiomeric purity (77-87% ee) of the products could be established only after derivatization. Primary alkenoic acid amides also underwent the epoxidation but gave the respective products in lower enantioselectivities (70% and 45% ee), presumably because the enantioface differentiation is hampered by the increased flexibility of the substrates, which exhibit two or three rotatable single bonds between the binding site and the reactive olefinic double bond.

  DOI：

  10.1021/ja305890c

文献信息

• 1,4-DI-SUBSTITUTED IMIDAZOLE DERIVATIVE
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：EP3312170A1

  公开（公告）日：2018-04-25

  The present invention provides a 1,4-disubstituted imidazole derivative of formula (1') wherein ring Q1 is optionally-substituted C6-10 aryl group, etc.; R1 and R2 are independently hydrogen atom, etc.; W1 is optionally-substituted C1-4 alkylene group; W2 is -NR3aC(O)- wherein R3a is hydrogen atom or C1-6 alkyl group, etc.; ring Q2 is 5- to 10-membered heteroaryl group, etc.; W3 is optionally-substituted C1-4 alkylene group, etc.; n is 1, 2, 3, 4, or 5; R4 is independently halogen atom, optionally-substituted C1-6 alkyl group, etc.; R5 is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.

  本发明提供了式(1')的1,4-二取代咪唑衍生物，其中环Q1为任选取代的C6-10芳基等；R1和R2独立地为氢原子等；W1为任选取代的C1-4亚烷基；W2为-NR3aC(O)-，其中R3a为氢原子或C1-6烷基等；环Q2为5至10元杂芳基等；W3为任选取代的C1-4亚烷基等；n为1、2、3、4或5；R4独立地为卤素原子、任选取代的C1-6烷基等。W3 是任选取代的 C1-4 亚烷基等；n 是 1、2、3、4 或 5；R4 独立地是卤素原子、任选取代的 C1-6 烷基等；R5 是羟基等；及其药理学上可接受的盐，它们对癌细胞的球形成能力具有强效抑制作用，可作为口服抗肿瘤药使用。
• 1,4-disubstituted imidazole derivative
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：US10807945B2

  公开（公告）日：2020-10-20

  The present invention provides a 1,4-disubstituted imidazole derivative of formula (1′) wherein ring Q1 is optionally-substituted C6-10 aryl group, etc.; R1 and R2 are independently hydrogen atom, etc.; W1 is optionally-substituted C1-4 alkylene group; W2 is —NR3aC(O)— wherein R3a is hydrogen atom or C1-6alkyl group, etc.; ring Q2 is 5- to 10-membered heteroaryl group, etc.; W3 is optionally-substituted C1-4 alkylene group, etc.; n is 1, 2, 3, 4, or 5; R4 is independently halogen atom, optionally-substituted C1-6 alkyl group, etc.; R5 is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.

  本发明提供了式(1′)的1，4-二取代咪唑衍生物，其中环Q1是任选取代的C6-10芳基等；R1和R2独立地是氢原子等；W1是任选取代的C1-4亚烷基等；W2是-NR3aC(O)-，其中R3a是氢原子或C1-6烷基等；环Q2是5-至10元杂芳基等；W3是任选取代的C1-4亚烷基等；n是1，2，3，4或5；R4独立地是卤素原子，任选取代的C1-6烷基等。W3 是任选取代的 C1-4 烯基等；n 是 1、2、3、4 或 5；R4 独立地是卤素原子、任选取代的 C1-6 烷基等；R5 是羟基等；及其药理上可接受的盐，它们对癌细胞的球形成能力具有强效抑制作用，可作为口服抗肿瘤药使用。
• US9828362B2
  申请人：——

  公开号：US9828362B2

  公开（公告）日：2017-11-28