1-benzyl-4-bromopyridin-2(1H)-one

• 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: 1-benzyl-4-bromopyridin-2(1H)-one
• 英文别名: 1‑benzyl‑4‑bromopyridin‑2(1H)‑one；1-Benzyl-4-bromopyridin-2(1H)-one；1-benzyl-4-bromopyridin-2-one
• 化学式: C₁₂H₁₀BrNO
• 分子量: 264.121
• InChiKey: OOMAPGBVJKYHKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-bromopyridin-2(1H)-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 tert-butyl (2-(((3-(1-benzyl-2-oxo-1,2-dihydropyridin-4-yl)- 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl)(methyl)carbamate
  参考文献：
  名称：

  作为PRMT1抑制剂的化合物及其应用

  摘要：

  本发明属于医药化学领域，涉及一类作为PRMT1抑制剂的化合物及其应用，具体地，本发明提供式(I)、式(II)、式(III)所示的化合物或其药学上可接受的盐、异构体、溶剂化物、结晶或前药，它们的制备方法以及含有这些化合物的药物组合物和这些化合物或组合物用于治疗由通过抑制PRMT1而改善的疾病如癌症的用途。

  公开号：

  CN116640094A
• 作为产物：
  描述：

  2-氨基-4-溴吡啶 在 硫酸 、 sodium hydride 、 sodium nitrite 作用下， 以 四氢呋喃 为溶剂， 反应 16.25h， 生成 1-benzyl-4-bromopyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of 2-aminopyridines bearing a pyridone moiety as potent ALK inhibitors to overcome the crizotinib-resistant mutants

  摘要：

  Despite the initial benefit demonstrated in clinical setting with ALK inhibitors, the challenging resistant mutants (F1174L, L1196M and G1202R) invariably developed. In this work, a series of 2-aminopyridine derivatives were designed and synthesized by C-5 position incorporation of a 2-pyridone moiety and bioisosteric replacement of the C-3 position linkers. Optimization of the 2-aminopyridine derivatives led to the identification of hit 18d displaying a significant growth inhibition against a variety of ALK-addicted cancer cells. Especially in the case of ALK-positive Karpas-299 cell, 18d exhibited excellent anti-proliferative potency with an IC50 value of about 40 nM. Moreover, 18d demonstrated encouraging activities against wild-type ALK (19 nM), ROS1 (2.3 nM) as well as challenging crizotinib-resistant ALK(L1196M) and ALK(G1202R) mutants with IC50 values of 45 nM and 22 nM, respectively. Additionally flow cytometric analysis indicates that 18d inhibited Karpas-299 cell viability via G1 phase arrest. Taken together, this work provided a promising ALK inhibitor to circumvent the clinical crizotinib-resistant mutants. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111734

文献信息

• Iridium-Catalysed C–H Borylation of 2-Pyridones; Bisfunctionalisation of CC4
  作者：Hugo Campello、Timothy Gallagher、Aurélien Honraedt、Worawat Niwetmarin、Cecilia Gotti

  DOI：10.1055/s-0036-1591594

  日期：2018.9

  Abstract The high regioselectivity associated with the iridium-catalysed borylation of pyridones has been exploited to provide a very direct and efficient entry to C(10) doubly substituted CC4 variants of cytisine. Two approaches have been evaluated based on (i) C–H activation of cytisine (or an N-substituted derivative) followed by N-alkylation (to enable dimer formation) and (ii) direct C–H activation and

  摘要 与铱催化的吡啶酮的硼化作用相关的高区域选择性已被利用来提供一个非常直接和有效的进入胱氨酸的C（10）双取代的CC4变体的途径。基于（i）半胱氨酸（或N-取代的衍生物）的C–H活化，随后的N-烷基化（以使二聚体形成）和（ii）CC4的直接C–H活化和硼化，已评估了两种方法。两种方法都提供了对C（10）-官能化CC4衍生物的访问，但是CC4的直接硼酸酯化允许更广泛的官能团互变。 与铱催化的吡啶酮的硼化作用相关的高区域选择性已被利用来提供一个非常直接和有效的进入胱氨酸的C（10）双取代的CC4变体的途径。基于（i）半胱氨酸（或N-取代的衍生物）的C–H活化，随后的N-烷基化（以使二聚体形成）和（ii）CC4的直接C–H活化和硼化，已评估了两种方法。两种方法都提供了对C（10）-官能化CC4衍生物的访问，但是CC4的直接硼酸酯化允许更广泛的官能团互变。
• <scp> PhICl ₂ </scp> / <scp> NH ₄ SCN‐Mediated </scp> Oxidative Regioselective Thiocyanation of Pyridin‐2( <scp> 1 <i>H</i> </scp> )‐ones
  作者：Shanqing Tao、Jiaxi Xiao、Yadong Li、Fengxia Sun、Yunfei Du

  DOI：10.1002/cjoc.202100278

  日期：2021.9

  The reaction of pyridin-2(1H)-ones with PhICl2 and NH4SCN enables an efficient regioselective thiocyanation, leading to the synthesis of the biologically interesting C5 thiocyanated 2-pyridones in good to high yields. The mechanistic pathway of this metal-free approach is postulated to involve the formation of the reactive thiocyanogen chloride from the reaction of PhICl2 and NH4SCN followed with the

  吡啶-2(1 H )-酮与PhICl 2和NH 4 SCN 的反应可实现有效的区域选择性硫氰化，从而以良好或高产率合成具有生物学意义的C5 硫氰化2-吡啶酮。这种无金属方法的机械途径被假定为涉及从 PhICl 2和 NH 4 SCN的反应形成反应性氯化硫氰，然后是吡啶-2(1 H )-一个环的区域选择性亲电硫氰化。
• 3-(1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
  申请人：Novartis AG

  公开号：US20190062309A1

  公开（公告）日：2019-02-28

  The present disclosure provides a compound of Formula (I′): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein R 1 , R 2 , R x , X 1 , n, n1, and q are as defined herein, and methods of making and using same.

  本公开提供化合物的化学式(I′)：或其药用可接受的盐、水合物、溶剂合物、前药、立体异构体或互变异构体，其中R1、R2、Rx、X1、n、n1和q如本文所定义，并提供制备和使用该化合物的方法。
• Electrolyte-free electrochemical C–H trifluoromethylation of 2-pyridones under batch and flow conditions
  作者：Elise Leclercq、Aurélien Moncomble、Céline Debavelaere、Mathieu Beaucamp、Maël Penhoat、Laëtitia Chausset-Boissarie

  DOI：10.1039/d2gc02326a

  日期：——

  direct C3 trifluoromethylation of 2-pyridones including unprotected derivatives by an electrochemical approach using the readily available Langlois reagent as the CF3 source in the absence of electrolytes. The trifluoromethylation under transition metal- and oxidant-free conditions occurred site-selectively to give the desired products in moderate to good yields under ambient conditions. Interestingly

  在此，我们报告了通过电化学方法在没有电解质的情况下使用现成的 Langlois 试剂作为 CF 3源对 2-吡啶酮（包括未保护的衍生物）进行直接 C3 三氟甲基化。在无过渡金属和无氧化剂的条件下，三氟甲基化发生位点选择性，从而在环境条件下以中等至良好的产率产生所需的产物。有趣的是，在微流体条件下实现了显着的加速率、提高的产量和选择性以及降低的能耗。
• Mild and Regioselective <i>N</i>-Alkylation of 2-Pyridones in Water
  作者：Xin Hao、Zhongmiao Xu、Hongfu Lu、Xuedong Dai、Ting Yang、Xichen Lin、Feng Ren

  DOI：10.1021/acs.orglett.5b01628

  日期：2015.7.17

  A mild and regioselective N-alkylation reaction of 2-pyridones in water has been developed. Tween 20 (2% w/w) was added to create a micellar system for improved solubility of starting materials, which leads to enhanced reaction rates. The protocol demonstrated a wide substrate scope with good isolated yield's (40-94%) for all of the 24 examples evaluated. High regioselectivity favoring N-alkylation over O-alkylation was observed for benzyl halides (>5:1), primary alkyl halides (>6:1), and bulky and less reactive secondary alkyl halides (>2.4:1).