3-Methoxy-5-(aminomethylcarbonyl)pyridine HCl salt

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-Methoxy-5-(aminomethylcarbonyl)pyridine HCl salt
• 英文别名: 2-amino-1-(5-methoxypyridin-3-yl)ethanone;hydrochloride
• 化学式: C₈H₁₀N₂O₂*ClH
• 分子量: 202.641
• InChiKey: BSHPEZGLOPWMEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Methoxy-5-(aminomethylcarbonyl)pyridine HCl salt 在 N-羟基-7-氮杂苯并三氮唑 、 硫酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-1-[(2S,4R)-4-Benzyl-5-((3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-4H-chromeno[4,3-d]oxazol-1-yl)-2-hydroxy-5-oxo-pentyl]-4-{1-[5-(5-methoxy-pyridin-3-yl)-oxazol-2-yl]-1-methyl-ethyl}-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
  参考文献：
  名称：

  The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resistant viral strains

  摘要：

  Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains. A meta-methoxy group on the pyridyl ring and a gem-dimethyl methyl linkage afforded compound 10 with notable in vitro antiviral activity against HIV-1 viral strains with reduced susceptibility to the clinically available PIs. Compound 10 also demonstrated favorable in vivo pharmacokinetics in animal models. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00474-8
• 作为产物：
  描述：

  3,5-二溴吡啶 在 盐酸 、 异丙基氯化镁 、 sodium methylate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Methoxy-5-(aminomethylcarbonyl)pyridine HCl salt
  参考文献：
  名称：

  Approaches to installing a N-gem-dimethylmethylene-2-oxazolyl group and application to the synthesis of a second generation HIV protease inhibitor

  摘要：

  Two syntheses of the title compound I were developed based on different approaches for installing the oxazole ring moiety. Formation and dehydration of ketoamide was initially used and scaled up to afford I on several kilogram scale, then oxazolyl anion/iminium coupling reaction was developed for a more convergent approach. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.01.103

文献信息

• Process for preparing piperazinepentaneamide HIV protease inhibitors
  申请人：——

  公开号：US20030144512A1

  公开（公告）日：2003-07-31

  A process for preparing &ggr;-hydroxy-4-[[2-oxazolyl]alkyl]-&agr;-[(cyclo)alkyl- or aryl- or heteroaryl-substituted methyl]-2-[[(un)substituted alkyl]aminocarbonyl]-1-piperazinepentanamides is disclosed. The piperazinepentanamides are useful as HIV protease inhibitors. A process for making a 4-[[2-oxazolyl]alkyl]-2-[[(un)substituted alkyl]aminocarbonyl]piperazine by treating a ketoamide precursor with fuming sulfuric acid in the presence of polyphosphoric acid is also disclosed. In addition, a process for enhancing the optical purity of 4-[[2-oxazolyl]alkyl]-2-[[(un)substituted alkyl]aminocarbonyl]-piperazines via the formation 2-naphthalenesulfonic acid crystal salts thereof is disclosed, as well as a method for purifying 2-naphthalenesulfonic acid.

  本发明公开了一种制备&ggr;-羟基-4-[[2-噁唑基]烷基]-&agr;-[(环)烷基-或芳基-或杂环芳基取代的甲基]-2-[[(非)取代的烷基]氨基甲酰-1-哌嗪戊酰胺的方法。哌嗪戊酰胺可用作HIV蛋白酶抑制剂。本发明还公开了一种通过在聚磷酸存在下用浓硫酸处理酮酰前体制备4-[[2-噁唑基]烷基]-2-[[(非)取代的烷基]氨基甲酰哌嗪的方法。此外，本发明还公开了一种通过形成2-萘磺酸晶体盐来增强4-[[2-噁唑基]烷基]-2-[[(非)取代的烷基]氨基甲酰哌嗪的光学纯度的方法，以及一种纯化2-萘磺酸的方法。
• US6649761B2
  申请人：——

  公开号：US6649761B2

  公开（公告）日：2003-11-18
• Approaches to installing a N-gem-dimethylmethylene-2-oxazolyl group and application to the synthesis of a second generation HIV protease inhibitor
  作者：Norihiro Ikemoto、Ross A. Miller、Fred J. Fleitz、Jinchu Liu、Daniel E. Petrillo、Joseph F. Leone、Joseph Laquidara、Benjamin Marcune、Sandor Karady、Joseph D. Armstrong、Ralph P. Volante

  DOI：10.1016/j.tetlet.2005.01.103

  日期：2005.3

  Two syntheses of the title compound I were developed based on different approaches for installing the oxazole ring moiety. Formation and dehydration of ketoamide was initially used and scaled up to afford I on several kilogram scale, then oxazolyl anion/iminium coupling reaction was developed for a more convergent approach. (C) 2005 Elsevier Ltd. All rights reserved.
• The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resistant viral strains
  作者：Fengqi Zhang、Kevin T. Chapman、William A. Schleif、David B. Olsen、Mark Stahlhut、Carrie A. Rutkowski、Lawrence C. Kuo、Lixia Jin、Jiunn H. Lin、Emilio A. Emini、James R. Tata

  DOI：10.1016/s0960-894x(03)00474-8

  日期：2003.8

  Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains. A meta-methoxy group on the pyridyl ring and a gem-dimethyl methyl linkage afforded compound 10 with notable in vitro antiviral activity against HIV-1 viral strains with reduced susceptibility to the clinically available PIs. Compound 10 also demonstrated favorable in vivo pharmacokinetics in animal models. (C) 2003 Elsevier Ltd. All rights reserved.