(S)-1,2,3,4-四氢喹啉-2-羧酸甲酯 | 63492-82-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-1,2,3,4-四氢喹啉-2-羧酸甲酯
• 英文名称: (S)-methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate
• 英文别名: methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate；methyl (S)-1,2,3,4-tetrahydroquinoline-2-carboxylate；(S)-1,2,3,4-Tetrahydroquinoline-2-carboxylic acid methyl ester；methyl (2S)-1,2,3,4-tetrahydroquinoline-2-carboxylate
• CAS: 63492-82-0
• 化学式: C₁₁H₁₃NO₂
• mdl: MFCD02684012
• 分子量: 191.23
• InChiKey: ACEPYLDNGYGKDY-JTQLQIEISA-N

物化性质

• 沸点：
  315.0±31.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  (S)-1,2,3,4-四氢喹啉-2-羧酸甲酯 在 咪唑 、 盐酸 、 lithium aluminium tetrahydride 、 氯化亚砜 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 24.17h， 生成 methyl (S)-1,2,3,4-tetrahydroquinoline-2-acetate
  参考文献：
  名称：

  Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor

  摘要：

  A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [H-3]- 5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (K-i = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (K-i = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (K-i = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (K-i = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (K-i = 2.3 nM) and 24g (K-i = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.

  DOI：

  10.1021/jm00049a015
• 作为产物：
  描述：

  2-喹啉甲酸甲酯 在 platinum(IV) oxide 、 α-chymotrypsine 、 氢气 作用下， 以 甲醇 为溶剂， 30.0 ℃ 、7.0 MPa 条件下， 反应 72.0h， 生成 (S)-1,2,3,4-四氢喹啉-2-羧酸甲酯
  参考文献：
  名称：

  对映选择性钌催化烯烃复分解的新型配体

  摘要：

  桥连接并有效地将手性从N杂环卡宾（NHC）的骨架传递到金属中心。结果是降冰片烯与烯丙基三甲基硅烷在钌催化的不对称开环交叉复分解中具有出色的对映选择性（参见方案）。

  DOI：

  10.1002/anie.201007673

文献信息

• Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-x_L Antagonist. 1. Manufacture of the Acid Moiety and Development of Some Key Reactions
  作者：Christophe Hardouin、Sandrine Baillard、François Barière、Chloé Copin、Anthony Craquelin、Solenn Janvier、Sylvain Lemaitre、Stéphane Le Roux、Olivier Russo、Sébastien Samson

  DOI：10.1021/acs.oprd.9b00364

  日期：2020.5.15

  Our efforts toward the process development of drug candidate 1 are described in a series of two papers. This manuscript focuses on the synthesis of kilogram quantities of acid precursor 2 to provide batches of material for preclinical studies and first-in-human clinical trials. Our approach relies on a chiral resolution to furnish the desired stereocenter, a cryogenic carboxylation, and N-alkylation

  我们在两篇论文中描述了我们对候选药物1的开发过程。该手稿侧重于千克量的酸前体2的合成，以提供批次的材料用于临床前研究和首次人体临床试验。我们的方法依赖于手性拆分以提供所需的立体中心，低温羧化和通过Suzuki偶联制备的氯化物衍生物26的N-烷基化。还讨论了进一步的努力，以改进那些可能成为更大规模问题的关键步骤。
• Novel Aryl Piperazine Derivatives With Medical Utility
  申请人：Campiani Giuseppe

  公开号：US20090238761A1

  公开（公告）日：2009-09-24

  This invention provides novel aryl piperazine derivatives having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D 3 , D 2 -like and 5-HT 2 receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders incl. schizophrenia.

  这项发明提供了具有医疗效用的新型芳基哌嗪衍生物，特别是作为多巴胺和5-羟色胺受体的调节剂，优选为D3、D2样和5-HT2受体亚型，特别适用于治疗包括精神分裂症在内的神经精神障碍。
• Enantioselective Copper-Catalyzed Intramolecular N−H Bond Insertion: Synthesis of Chiral 2-Carboxytetrahydroquinolines
  作者：Xiao-Guang Song、Yuan-Yuan Ren、Shou-Fei Zhu、Qi-Lin Zhou

  DOI：10.1002/adsc.201600390

  日期：2016.7.28

  realized by using copper catalysts modified with chiral spirobisoxazoline ligands, which provides a novel strategy for the synthesis of chiral 2‐carboxytetrahydroquinolines. This reaction features fast reaction rate, high yield, high enantioselectivity, and mild reaction conditions.

  通过使用经手性螺双二恶唑啉配体改性的铜催化剂，实现了第一个高度对映选择性的分子内NH键插入，这为手性2-羧基四氢喹啉的合成提供了新的策略。该反应具有反应速度快，产率高，对映选择性高和反应条件温和的特点。
• Enzymatic resolution of 2-substituted tetrahydroquinolines. Convenient approaches to tricyclic quinoxalinediones as potent NMDA-glycine antagonists
  作者：Seiji Katayama、Nobuyuki Ae、Ryu Nagata

  DOI：10.1016/s0957-4166(98)00484-4

  日期：1998.12

  class of NMDA-glycine antagonists using enzymatic resolutions are described. An intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate 3, was resolved to (S)-3 in 97% ee and 47% yield (E=67) using α-chymotrypsin. In an improved method, hydrolysis of another intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-acetate 4, with Novozym® 435 provided the desired (S)-4 in high enantioselectivity

  描述了使用酶促拆分导致对映体纯的三环喹喔啉二酮类NMDA-甘氨酸拮抗剂的两种方法。使用α-胰凝乳蛋白酶将中间体1,2,3,4-四氢喹啉-2-羧酸外消旋甲基1,2,3,4-四氢喹啉-2-羧酸酯3拆分为（S）-3，收率为97％ee，收率为47％（E = 67）。在一个改进的方法中，另一种中间体，外消旋甲基-1,2,3,4-四氢喹啉-2-乙酸乙酯水解4，用的Novozym ® 435提供所需的（小号） - 4在高对映选择性和产率（93％ee的，50 ％，E = 94）。
• B(C 6 F 5 ) 3 -catalyzed metal-free hydrogenations of 2-quinolinecarboxylates
  作者：Caifang Han、E. Zhang、Xiangqing Feng、Shoufeng Wang、Haifeng Du

  DOI：10.1016/j.tetlet.2018.02.057

  日期：2018.4

  A metal-free hydrogenation of 2-quinolinecarboxylates has been realized by using 5 mol% of B(C6F5)3 as catalyst. A variety of tetrahydroquinolines were obtained in 57–99% yields. An attempt for the asymmetric hydrogenation with chiral boron Lewis acids generated from chiral dienes afforded very low ee’s.

  通过使用5mol％的B（C 6 F 5）3作为催化剂，已经实现了2-喹啉羧酸酯的无金属氢化。以57–99％的收率获得了各种四氢喹啉。尝试用手性二烯生成的手性硼不对称氢化路易斯酸可提供非常低的ee。