(S)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline | 1190876-63-1

• 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: (S)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline
• 英文别名: (2S)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline
• CAS: 1190876-63-1
• 化学式: C₁₀H₁₂BrN
• 分子量: 226.116
• InChiKey: QWGAZLNZSGHSGE-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline 在 tris-(dibenzylideneacetone)dipalladium(0) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 氨 、 potassium acetate 、 potassium carbonate 、 三乙胺 、 三环己基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.17h， 生成 4-[(2S)-6-(2-chloro-5-methylpyrimidin-4-yl)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carbonyl]benzene-1,3-diol
  参考文献：
  名称：

  Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase

  摘要：

  Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, k(d)) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1 alpha subunit in the PC3 cancer cell line in vitro.

  DOI：

  10.1021/acs.jmedchem.6b01478
• 作为产物：
  描述：

  1,2,3,4-四氢喹哪啶 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 水 、 异丙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 (S)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase

  摘要：

  Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, k(d)) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1 alpha subunit in the PC3 cancer cell line in vitro.

  DOI：

  10.1021/acs.jmedchem.6b01478

文献信息

• A one-pot process for the enantioselective synthesis of tetrahydroquinolines and tetrahydroisoquinolines <i>via</i> asymmetric reductive amination (ARA)
  作者：Tao Yang、Qin Yin、Guoxian Gu、Xumu Zhang

  DOI：10.1039/c8cc03586e

  日期：——

  Asymmetric reductive amination for the synthesis of both chiral tetrahydroquinolines (THQs) and tetrahydroisoquinolines (THIQs) has been realized with an Ir/ZhaoPhos catalytic system via a one-pot N-Boc deprotection/intramolecular asymmetric reductive amination (ARA) sequence. Control experiments reveal that HCl plays a vital role to the success of this transformation. The HCl acid assists the removal

  Ir / ZhaoPhos催化体系通过一锅N - Boc脱保护/分子内不对称还原胺化（ARA）序列实现了用于合成手性四氢喹啉（THQs）和四氢异喹啉（THIQs）的不对称还原胺化。对照实验表明，HCl对这种转化的成功起着至关重要的作用。HCl酸有助于除去N- Boc保护基，还提供氯离子与ZhaoPhos中的硫脲部分相互作用，从而实现出色的反应对映控制。
• pH-Regulated Asymmetric Transfer Hydrogenation of Quinolines in Water
  作者：Chao Wang、Chaoqun Li、Xiaofeng Wu、Alan Pettman、Jianliang Xiao

  DOI：10.1002/anie.200902570

  日期：2009.8.17

  In buffered water, a broad range of quinoline derivatives underwent asymmetric transfer hydrogenation in air with the rhodium catalyst 1 and sodium formate as the hydrogen source to furnish synthetically important 1,2,3,4‐tetrahydroquinolines with excellent enantioselectivities (see scheme; R=H, Me, F, Cl, Br, OMe; R′=alkyl, aryl).

  在缓冲水中，各种各样的喹啉衍生物在空气中以铑催化剂1和甲酸钠作为氢源进行不对称转移加氢，以提供具有重要对映选择性的重要合成1,2,3,4-四氢喹啉（参见方案； R = H，Me，F，Cl，Br，OMe； R'＝烷基，芳基）。
• Manganese‐Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π–π Interaction**
  作者：Chenguang Liu、Mingyang Wang、Shihan Liu、Yujie Wang、Yong Peng、Yu Lan、Qiang Liu

  DOI：10.1002/anie.202013540

  日期：2021.3

  The non‐noble metal‐catalyzed asymmetric hydrogenation of N‐heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity

  报道了非贵金属催化的N-杂芳族化合物喹啉的不对称氢化。一种新型手性钳式锰催化剂在喹啉的不对称氢化中表现出出色的催化活性，提供了高收率和对映选择性（高达97％ee）。在低催化剂负载量（S / C = 4000）下，达到了3840的周转率，与该反应中最有效的贵金属催化剂的活性相竞争。对映选择性的精确调节通过π-π相互作用来保证。
• Brønsted acid differentiated metal catalysis by kinetic discrimination
  作者：Magnus Rueping、René M. Koenigs

  DOI：10.1039/c0cc02167a

  日期：——

  A Brønsted acid differentiated metal catalyzed hydrogenation has been developed. A combinatorial variation of chiral triflylamides with achiral metal complexes results in a highly active catalyst for the asymmetric reduction.

  一种布朗斯特酸催化的金属催化氢化反应已被开发。手性三氟甲基酰胺与非手性金属复合物的组合变体产生了一种高活性的催化剂，用于不对称还原反应。
• Strong Brønsted acid promoted asymmetric hydrogenation of isoquinolines and quinolines catalyzed by a Rh–thiourea chiral phosphine complex via anion binding
  作者：Jialin Wen、Renchang Tan、Shaodong Liu、Qingyang Zhao、Xumu Zhang

  DOI：10.1039/c5sc04712a

  日期：——

  Rhodium catalyzed asymmetric hydrogenation of both isoquinolines and quinolines provides a new method to synthesize chiral tetrahydroisoquinolines and tetrahydroquinolines. By introducing strong Brønsted acid HCl, anion binding between the substrate and the ligand was established to achieve high reactivity and high enantioselectivity (up to 99% conversion and 99% ee). An NMR study suggests an anion

  铑催化异喹啉和喹啉的不对称加氢提供了一种合成手性四氢异喹啉和四氢喹啉的新方法。通过引入强布朗斯台德酸HCl，在底物和配体之间建立了阴离子结合，以实现高反应性和高对映选择性（高达99％的转化率和99％的ee）。NMR研究表明催化剂与底物之间存在阴离子结合。氘标记实验揭示了可能的反应途径。