4-fluoro-11H-pyrido[2,1-b]quinazolin-11-one | 1609121-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 4-fluoro-11H-pyrido[2,1-b]quinazolin-11-one
• 英文别名: 4-Fluoropyrido[2,1-b]quinazolin-11-one；4-fluoropyrido[2,1-b]quinazolin-11-one
• CAS: 1609121-10-9
• 化学式: C₁₂H₇FN₂O
• 分子量: 214.199
• InChiKey: HNCDFJGLXRQYGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(2-fluorophenyl)pyridin-2-amine 、 一氧化碳 在 dipotassium peroxodisulfate 、 palladium diacetate 作用下， 以 三氟乙酸 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 以77%的产率得到4-fluoro-11H-pyrido[2,1-b]quinazolin-11-one
  参考文献：
  名称：

  Palladium-Catalyzed C(sp²)–H Pyridocarbonylation of N-Aryl-2-aminopyridines: Dual Function of the Pyridyl Moiety

  摘要：

  An efficient synthesis of 11H-pyrido[2,1-b]-quinazolin-11-one through palladium-catalyzed C(sp(2))-H pyridocarbonylation of N-aryl-2-aminopyridines has been developed. The pyridyl group acts as an intramolecular nucleophile for the first time in C-H carbonylation reactions.

  DOI：

  10.1021/ol501070g

文献信息

• Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction
  作者：Meilin Liu、Miaomiao Shu、Chaochao Yao、Guodong Yin、Dunjia Wang、Jinkun Huang

  DOI：10.1021/acs.orglett.6b00113

  日期：2016.2.19

  simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C–N/C–C bond cleavage and two C–N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms

  通过Cu（OAc）2 ·H 2 O催化易得的取代的靛红与2-溴吡啶衍生物的反应，可以简单，有效地合成11 H-吡啶并[ 2,1 - b ]喹唑啉-11-酮。该反应在一锅操作中涉及C–N / CC键断裂和两个C–N键形成。该方法是对先前报道的合成方法的补充，并讨论了两个合理的反应机理。
• Base-Controlled Selectivity in the Synthesis of Linear and Angular Fused Quinazolinones by a Palladium-Catalyzed Carbonylation/Nucleophilic Aromatic Substitution Sequence
  作者：Jianbin Chen、Kishore Natte、Anke Spannenberg、Helfried Neumann、Peter Langer、Matthias Beller、Xiao-Feng Wu

  DOI：10.1002/anie.201402779

  日期：2014.7.14

  A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium‐catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light‐induced 4+4 reaction of the

  描述了一种新的方法，该方法可通过钯催化的羰基化偶联，然后进行分子内亲核芳族取代，轻松合成稠合的喹唑啉酮骨架。该基团起着关键的调节剂的作用：DBU产生线性异构体，而Et 3 N则促进了优先形成角产物。有趣的是，还观察到了产物的光诱导4 + 4反应。
• Palladium-Catalyzed Carbonylative Synthesis of <i>N</i> -Heterocycles from 1-Chloro-2-fluorobenzenes
  作者：Yang Yuan、Xiao-Feng Wu

  DOI：10.1002/ejoc.201900232

  日期：2019.3.21

  A simple and efficient methodology for the synthesis of pyrido‐fused quinazolinones and dibenzoxazepinones has been developed. By palladium‐catalyzed carbonylation/nucleophilic aromatic substitution reaction sequence, and with 1‐chloro‐2‐fluorobenzenes and 2‐aminopyridines or 2‐aminophenols as the starting materials, good yields of the desired products were be obtained.

  已开发出一种简单有效的方法，用于合成吡啶基稠合的喹唑啉酮和二苯并恶嗪酮。通过钯催化的羰基化/亲核芳族取代反应序列，并以1-氯-2-氟代苯和2-氨基吡啶或2-氨基酚为起始原料，可获得所需产物的良好收率。
• Efflux pump inhibition by 11H-pyrido[2,1-b]quinazolin-11-one analogues in mycobacteria
  作者：Tejosmita Sen、Kashmiri Neog、Sangita Sarma、Prasenjit Manna、Hari Prasanna Deka Boruah、Pranjal Gogoi、Anil Kumar Singh

  DOI：10.1016/j.bmc.2018.08.034

  日期：2018.9

  Mycobacterium tuberculosis infection causes 1.8 million deaths worldwide, of which half a million has been diagnosed with resistant tuberculosis (TB). Emergence of multi drug resistant and extensive drug resistant strains has made all the existing anti-TB therapy futile. The major involvement of efflux pump in drug resistance has made it a direct approach for therapeutic exploration against resistant M. tuberculosis. This study demarcates the role of 11H-pyrido[2,1-b]quinazolin-11-one (quinazolinone) analogues as efflux pump inhibitor in Mycobacterium smegmatis. Sixteen quinazolinone analogues were synthesized by treating 2-aminopyridine and 2fluorobenzonitrile with (KOBu)-O-t. Analogues were tested, and 3a, 3b, 3c, 3g, 3j, 31, 3m, and 3p were found to modulate EtBr MIC by > 4 whereas 3a, 3g, 3i and 3o showed > 4 modulation on norfloxacin MIC. 31 and 3o in addition to their very low toxicity they showed high EtBr and norfloxacin accumulation respectively. Time kill curve showed effective log reduction in colony forming unit in presence of these analogues, thus confirming their role as efflux pump inhibitor. Through docking and alignment studies, we have also shown that the LfrA amino acid residues that the analogues are interacting with are present in Rv2333c and Rv2846c of M. tuberculosis. This study have shown for the first time the possibility of developing the 11H-pyrido[2,1-b]quinazolin-11-one analogues as efflux pump inhibitors for M. smegmatis and hence unbolts the scope to advance this study against resistant M. tuberculosis as well.
• Palladium-Catalyzed C(sp²)–H Pyridocarbonylation of <i>N</i>-Aryl-2-aminopyridines: Dual Function of the Pyridyl Moiety
  作者：Dongdong Liang、Yimiao He、Qiang Zhu

  DOI：10.1021/ol501070g

  日期：2014.5.16

  An efficient synthesis of 11H-pyrido[2,1-b]-quinazolin-11-one through palladium-catalyzed C(sp(2))-H pyridocarbonylation of N-aryl-2-aminopyridines has been developed. The pyridyl group acts as an intramolecular nucleophile for the first time in C-H carbonylation reactions.