(S)-4-{1-[5-(5-Methoxy-pyridin-3-yl)-oxazol-2-yl]-1-methyl-ethyl}-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide | 552887-85-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-4-{1-[5-(5-Methoxy-pyridin-3-yl)-oxazol-2-yl]-1-methyl-ethyl}-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
• 英文别名: (2S)-4-[2-[5-(5-methoxypyridin-3-yl)-1,3-oxazol-2-yl]propan-2-yl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
• CAS: 552887-85-1
• 化学式: C₁₉H₂₄F₃N₅O₃
• 分子量: 427.426
• InChiKey: ROPVTWOBDHIKON-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-4-{1-[5-(5-Methoxy-pyridin-3-yl)-oxazol-2-yl]-1-methyl-ethyl}-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide 在 盐酸 、 甲醇 、 2-甲基-2-丁醇 作用下， 反应 96.0h， 生成 (αR,γS,2S)-N-[(3S,4S)-3,4-dihydro-3-hydroxy-2H-1-benzopyran-4-yl]-γ-hydroxy-4-[1-[5-(5-methoxy-3-pyridinyl)-2-oxazolyl]-1-methylethyl]-α-(phenylmethyl)-2-[[(2,2,2-trifluoroethyl)amino]carbonyl]-1-piperazinepentanamide
  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
• 作为产物：
  描述：

  (2S)-4-[2-[5-(5-methoxypyridin-3-yl)-1,3-oxazol-2-yl]propan-2-yl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide;naphthalene-2-sulfonic acid 在 甲醇 、 氢氧化钾 作用下， 生成 (S)-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：

  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。
• Hydrohalide salts of an HIV protease inhibitor
  申请人：——

  公开号：US20030125336A1

  公开（公告）日：2003-07-03

  Pharmaceutically acceptable hydrochloride and hydrobromide salts of Compound A are disclosed, wherein Compound A is of formula: 1 Compound A and its hydrobromide and hydrochloride salts are HIV protease inhibitors useful for preventing or treating HIV infection, for delaying the onset of AIDS, and for treating AIDS. Pharmaceutical compositions employing the crystalline salts, and processes for making and using the crystalline salts are also disclosed.

  本文披露了化合物A的药用可接受的盐酸盐和溴化盐，其中化合物A的化学式为：1。化合物A及其溴化盐和盐酸盐是HIV蛋白酶抑制剂，可用于预防或治疗HIV感染，延缓艾滋病的发作，并用于治疗艾滋病。本文还披露了使用晶体盐的制药组合物以及制备和使用晶体盐的方法。
• P1′ oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1
  作者：Ronald M. Kim、Elizabeth A. Rouse、Kevin T. Chapman、William A. Schleif、David B. Olsen、Mark Stahlhut、Carrie A. Rutkowski、Emilio A. Emini、James R. Tata

  DOI：10.1016/j.bmcl.2004.06.092

  日期：2004.9

  HIV-1 protease inhibitors (PI's) bearing 1,3,4-oxadiazoles at the P1' position were prepared by a novel method involving the diastereoselective installation of a carboxylic acid and conversion to the P1' heterocycle. The compounds are picomolar inhibitors of native HIV-1 protease, with most of the compounds maintaining excellent antiviral activity against a panel of PI-resistant strains. (C) 2004 Elsevier Ltd. All rights reserved.
• GAMMA-HYDROXY-2-(FLUOROALKYLAMINOCARBONYL)-1-PIPERAZINEPENTANAMIDES AS HIV PROTEASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1242426B1

  公开（公告）日：2007-10-31
• US6649761B2
  申请人：——

  公开号：US6649761B2

  公开（公告）日：2003-11-18