(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 | 342602-11-3

• 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)-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
• 英文别名: (2S)-1-[(2S,4R)-5-[(3aS,9bS)-2,2-dimethyl-4,9b-dihydro-3aH-chromeno[4,3-d][1,3]oxazol-1-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-4-[2-[5-(5-methoxypyridin-3-yl)-1,3-oxazol-2-yl]propan-2-yl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
• CAS: 342602-11-3
• 化学式: C₄₃H₅₁F₃N₆O₇
• 分子量: 820.909
• InChiKey: OHZDZGCFOVLLMN-YJRJYRRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  59
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (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 在 盐酸 、 甲醇 、 醋酸异丙酯 作用下， 以 异丙醇 为溶剂， 以79%的产率得到(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：

  3-Methoxy-5-(t-butyloxycarbonylaminomethylcarbonyl)-pyridine 在 盐酸 、 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 甲醇 、 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

文献信息

• 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.