tert-butyl 3-(4-methylquinolin-2-yl)azetidine-1-carboxylate | 1180653-80-8

• 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: tert-butyl 3-(4-methylquinolin-2-yl)azetidine-1-carboxylate
• CAS: 1180653-80-8
• 化学式: C₁₈H₂₂N₂O₂
• 分子量: 298.385
• InChiKey: NWUNNTKVXJCNMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(4-methylquinolin-2-yl)azetidine-1-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (E)-6-(3-(3-(4-methylquinolin-2-yl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors

  摘要：

  A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.

  DOI：

  10.1016/j.ejmech.2014.07.036
• 作为产物：
  描述：

  1-Boc-3-碘氮杂环丁烷 在 dipotassium peroxodisulfate 、 copper(l) iodide 、 lithium methanolate 、 silver nitrate 、 三氟乙酸 作用下， 以 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 tert-butyl 3-(4-methylquinolin-2-yl)azetidine-1-carboxylate
  参考文献：
  名称：

  有机三氟硼酸基砌块的合成及微反应

  摘要：

  铜催化的各种有机卤化物与双（频哪醇）二硼的硼化反应可以制备多种有机三氟硼酸钾。这些反应温和且通用，可提供各种有趣的含硼结构单元，包括那些含有哌啶、吡咯、氮杂环丁烷、四氢吡喃和氧杂环丁烷亚结构的结构单元。报告了选定实例的代表性 Minisci 反应。

  DOI：

  10.1021/jo4005519

文献信息

• Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via <i>N</i>-(Acyloxy)phthalimides
  作者：Trevor C. Sherwood、Ning Li、Aliza N. Yazdani、T. G. Murali Dhar

  DOI：10.1021/acs.joc.8b00205

  日期：2018.3.2

  one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to

  已经开发了一种改进的一锅式Minisci反应，该反应使用可见光，有机光催化剂和羧酸作为自由基前体，通过原位生成的N-（酰氧基）邻苯二甲酰亚胺进行中介。所采用的条件是温和的，表现出高度的官能团耐受性，并且不需要大量过量的羧酸反应物。结果，该反应可以应用于具有敏感官能团的药物样支架和分子，从而可以进行后期功能化，这在药物化学中引起了极大的兴趣。
• Visible-Light-Initiated Manganese Catalysis for C−H Alkylation of Heteroarenes: Applications and Mechanistic Studies
  作者：Philippe Nuhant、Martins S. Oderinde、Julien Genovino、Antoine Juneau、Yohann Gagné、Christophe Allais、Gary M. Chinigo、Chulho Choi、Neal W. Sach、Louise Bernier、Yvette M. Fobian、Mark W. Bundesmann、Bhagyashree Khunte、Mathieu Frenette、Olugbeminiyi O. Fadeyi

  DOI：10.1002/anie.201707958

  日期：2017.11.27

  A visible‐light‐driven Minisci protocol that employs an inexpensive earth‐abundant metal catalyst, decacarbonyldimanganese Mn2(CO)10, to generate alkyl radicals from alkyl iodides has been developed. This Minisci protocol is compatible with a wide array of sensitive functional groups, including oxetanes, sugar moieties, azetidines, tert‐butyl carbamates (Boc‐group), cyclobutanes, and spirocycles. The

  已经开发了一种可见光驱动的Minisci协议，该协议采用了廉价的地球上富足的金属催化剂十羰基二锰Mn 2（CO）10从烷基碘生成烷基。该Minisci方案与各种敏感的官能团兼容，包括氧杂环丁烷，糖部分，氮杂环丁烷，氨基甲酸叔丁酯（Boc组），环丁烷和螺环。复杂的含氮药物的后期功能化证明了该方案的鲁棒性。光物理和DFT研究表明，光传播的链反应机制由传播。Mn（CO）5。限速步骤是通过碘从烷基碘中提取碘。Mn（CO）5。
• Visible-light-mediated Minisci C–H alkylation of heteroarenes with unactivated alkyl halides using O₂ as an oxidant
  作者：Jianyang Dong、Xueli Lyu、Zhen Wang、Xiaochen Wang、Hongjian Song、Yuxiu Liu、Qingmin Wang

  DOI：10.1039/c8sc04892d

  日期：——

  visible-light-mediated Minisci C–H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive functional groups and has a broad substrate scope. Notably, functionalization of (iso)quinolines, pyridines, phenanthrolines, quinazoline, and other heterocyclic compounds with unactivated primary, secondary

  在此，我们报告了一种在室温下使用分子氧作为氧化剂，用未活化的卤代烷对杂芳烃进行直接可见光介导的 Minisci C-H 烷基化的方案。这种温和的方案与多种敏感官能团兼容，并且具有广泛的底物范围。值得注意的是，（异）喹啉、吡啶、菲咯啉、喹唑啉和其他杂环化合物与未活化的伯、仲和叔烷基卤化物的官能化在标准条件下顺利进行。复杂的含氮天然产物和药物的后期功能化进一步证明了该协议的稳健性。
• Preparation of Heteroaryloxetanes and Heteroarylazetidines by Use of a Minisci Reaction
  作者：Matthew A. J. Duncton、M. Angels Estiarte、Russell J. Johnson、Matthew Cox、Donogh J. R. O’Mahony、William T. Edwards、Michael G. Kelly

  DOI：10.1021/jo9010624

  日期：2009.8.21

  Introduction of oxetan-3-yl and azetidin-3-yl groups into heteroaromatic bases was achieved by using a radical addition method (Minisci reaction). To demonstrate utility. the process was used to introduce an oxetane Or azetidine into heteroaromatic systems that have found important uses in the drug discovery industry, such as the marketed EGFR inhibitor geftinib, a quinolinecarbonitrile Src tyrosine kinase inhibitor, and the antimalarial hydroquinine.
• Synthesis and Minisci Reactions of Organotrifluoroborato Building Blocks
  作者：Marc Presset、Nicolas Fleury-Brégeot、Daniel Oehlrich、Frederik Rombouts、Gary A. Molander

  DOI：10.1021/jo4005519

  日期：2013.5.3

  bis(pinacolato)diboron allows the preparation of diverse potassium organotrifluoroborates. The reactions are mild and general, providing access to a variety of interesting, boron-containing building blocks, including those containing piperidine, pyrrole, azetidine, tetrahydropyran, and oxetane substructures. Representative Minisci reactions are reported for select examples.

  铜催化的各种有机卤化物与双（频哪醇）二硼的硼化反应可以制备多种有机三氟硼酸钾。这些反应温和且通用，可提供各种有趣的含硼结构单元，包括那些含有哌啶、吡咯、氮杂环丁烷、四氢吡喃和氧杂环丁烷亚结构的结构单元。报告了选定实例的代表性 Minisci 反应。