2-amino-5-methyl-phenylphosphonic acid diethylester | 42822-58-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-5-methyl-phenylphosphonic acid diethylester
• 英文别名: 2-amino-5-methylphenylphosphonic acid diethylester；diethyl (2-amino-5-methylphenyl)phosphonate；diethyl 2-amino-5-methylphenylphosphonate；Diethyl-2-amino-5-methylphenylphosphonat；2-Diethoxyphosphoryl-4-methylaniline
• CAS: 42822-58-2
• 化学式: C₁₁H₁₈NO₃P
• 分子量: 243.243
• InChiKey: VBZDSGNZIWOBAL-UHFFFAOYSA-N

物化性质

• 沸点：
  357.0±35.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-5-methyl-phenylphosphonic acid diethylester 在 lithium aluminium tetrahydride 、 水 、 对甲苯磺酸 作用下， 以 乙醚 、 水 、 甲苯 为溶剂， 反应 96.0h， 生成 1,5-dimethyl-1H-1,3-benzazaphosphole
  参考文献：
  名称：

  σ2-P Ligands: convenient syntheses of N-methyl-1,3-benzazaphospholes

  摘要：

  A convenient three-step route to 1,5-dimethyl-1,3-benzazaphosphole via Cu- or Pd-catalyzed phosphonylation of 2-iodo-4-methylaniline, reduction to 2-phosphino-4-methylaniline, and disproportionative cyclization with excess formaldehyde is reported. N-Methylbenzazaphospholes can be functionalized in the 2-position via alpha-CH-lithiation with tBuLi and are pi-acidic sigma P-2-ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.07.037
• 作为产物：
  描述：

  2-溴-4-甲基-1-硝基苯 在 palladium on activated charcoal 、 氢气 、 palladium diacetate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 0.5h， 生成 2-amino-5-methyl-phenylphosphonic acid diethylester
  参考文献：
  名称：

  发现苯并磷二嗪候选药物 IDX375：一种新型丙型肝炎变构 NS5B RdRp 抑制剂。

  摘要：

  丙型肝炎病毒 (HCV) NS5B RNA 依赖性 RNA 聚合酶 (RdRp) 在病毒复制中起核心作用。NS5B 在哺乳动物细胞中没有功能等效物，因此是一个有吸引力的选择性抑制靶标。本文描述了一种新的 HCV NS5B 非核苷抑制剂家族的发现，其灵感来自磺胺和膦酰胺之间的生物等排性。这个新系列的系统结构优化导致了 IDX375 的鉴定，这是一种对基因型 1a 和 1b 具有选择性的强效非核苷抑制剂。IDX375的结构和结合域通过X射线共结晶研究得到证实。

  DOI：

  10.1016/j.bmcl.2017.01.017

文献信息

• [EN] METHODS AND COMPOSITIONS FOR THE REMOVAL OF ALDEHYDE ADDUCTS AND CROSSLINKS FROM BIOMOLECULES<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR L'ÉLIMINATION DE PRODUITS D'ADDITION ET DE RÉTICULATION D'ALDÉHYDE DE MOLÉCULES BIOLOGIQUES
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2016044313A1

  公开（公告）日：2016-03-24

  Methods are provided for reducing the number of aldehyde adducts and/or crosslinks from fixed biomolecules. In some cases, subject methods include contacting a sample having aldehyde fixed biomolecules (e.g., a biological sample such as a formalin fixed paraffin embedded (FFPE) tissue sample) with an adduct reversal agent in an amount and for a period of time sufficient to reduce the number of aldehyde fixation related adducts and/or crosslinks in the sample. In some cases, the adduct reversal agent is a compound that includes an aromatic ring and at least one of: an amine group and a proton-donating group. In some cases, the adduct reversal agent is a compound selected from the compounds of Table 1. Compositions and kits for practicing the subject methods are also provided.

  本发明提供了减少固定生物分子中醛基加合物和/或交联物数量的方法。在某些情况下，所述方法包括将含有醛固定生物分子（例如生物样品，如福尔马林固定石蜡嵌入（FFPE）组织样品）的样品与加合物逆转剂接触，所述逆转剂的用量和时间足以减少样品中醛固定相关的加合物和/或交联物的数量。在某些情况下，所述加合物逆转剂是一种化合物，其包括芳香环和至少一个以下物质之一：胺基和质子供体基团。在某些情况下，所述加合物逆转剂是从表1中选择的化合物之一。还提供了用于实施所述方法的组合物和试剂盒。
• [EN] PHOSPHADIAZINE HCV POLYMERASE INHIBITORS IV<br/>[FR] INHIBITEURS IV DE LA PHOSPHADIAZINE POLYMÉRASE VHC
  申请人：IDENIX PHARMACEUTICALS INC

  公开号：WO2009032180A1

  公开（公告）日：2009-03-12

  Provided herein are phosphadiazine polymerase inhibitor, for example, of any of Formulas (IV), (IV), (I'), (II'), or (IVa), pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

  本文提供了磷二氮杂环聚合酶抑制剂，例如任何公式(IV)，(IV)，(I')，(II')或(IVa)中的化合物，以及包含这些化合物的制药组合物和制备方法。还提供了它们用于治疗宿主中需要治疗HCV感染的方法。
• Solvent-controlled lithiation of PC–N-heterocycles: Synthesis of mono- and bis(trimethylsilyl)-tert-butyl-dihydrobenzazaphospholes – A new type of highly bulky and basic phosphine ligands
  作者：Mohammed Ghalib、Peter G. Jones、Joachim W. Heinicke

  DOI：10.1016/j.jorganchem.2014.04.014

  日期：2014.8

  The influence of solvents on the lithiation of N-methyl-1,3-benzazaphospholes is reported; these are accessible via catalytic phosphonylation of 2-bromoanilines, subsequent reduction to 2-phosphinoanilines and acid-catalysed disproportionative ring closure with excess paraformaldehyde. Reactions with tBuLi in polar solvents (THF, Et2O), particularly in the presence of tBuOK, lead to 2-lithiobenzazaphospholes (CH-lithiation) whereas hydrocarbons favour "normal" (hexane) or "inverse" (toluene) addition at the P=C bond. Reactive Li-species were trapped by ClSiMe3, present during the lithiation in hydrocarbons, and give rise to 2- and 3-trimethylsilyl-dihydro-1,3-benzazaphospholes, respectively. In hexane, via preferred lithiation of the primary adduct, the 2,2'-bis(trimethylsilyl)-dihydro-1,3-benzazaphosphole is the main product. 5-Methyl-1,3-benzazaphosphole, with NH function, reacts in toluene in the "normal" mode to 3-tert-butyl-1,2-bis(trimethylsilyl)-5-methyl-dihydrobenzazaphosphole. The sterically demanding tert-butyl and trimethylsilyl groups are arranged in anti-position as shown by crystal structure analyses, the second 2-SiMe3 group in gauche position. The P-tert-butyl-2,2'-bis(trimethylsilyl)-dihydrobenzazaphospholes represent a new type of sterically congested dialkylaryl phosphine ligands with increased basicity by the +I-effect of the silyl groups and +M-effect of the basic nitrogen in o-position. (C) 2014 Elsevier B.V. All rights reserved.
• Coplanar Tetracyclic π‐Excess σ ² P Ligands
  作者：Basit Niaz、Fatima Iftikhar、Markus K. Kindermann、Peter G. Jones、Joachim Heinicke

  DOI：10.1002/ejic.201300342

  日期：2013.8.12

  AbstractThe acid‐catalyzed reactions of 5‐methyl‐2‐phosphanylaniline (1) with dialdehydes were studied. Whereas the reaction with glyoxal provides a mixture of two 1H‐1,3‐benzazaphospholes, 2 and 3, by concomitant reduction of a CHO group and C–C bond cleavage, respectively, the reaction with o‐phthalic dicarbaldehyde provided in excellent yield the tetracyclic planar benzazaphosphole 4, which was characterized by crystal structure analysis. The active hydrogen atoms, delivered by aromatization of a dihydrobenzazaphosphole intermediate, forms an N–CH2 bridge by reductive N‐alkylation. Pyridine‐2,6‐dicarbaldehyde reacts analogously but not chemoselectively and, thus, gives two isomers 5 and 6. Condensation with pyridine‐2,6‐dicarbaldehyde afforded the bis(benzazaphosphole)pyridine pincer ligand 7, but along with 2‐(benzazaphospholyl)‐6‐tolylpyridine (8) by partial P–C bond cleavage. The high upfield 31P NMR chemical shift of 4 compared to those of normal benzazaphospholes indicates it to be a particularly π‐rich σ2P ligand.
• PHOSPHADIAZINE HCV POLYMERASE INHIBITORS IV
  申请人：IDENIX Pharmaceuticals, Inc.

  公开号：EP2183260A1

  公开（公告）日：2010-05-12