tert-butyl (3S)-4-{(2S,4R)-4-benzyl-5-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-hydroxy-5-oxopentyl}-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate | 342600-52-6

• 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: tert-butyl (3S)-4-{(2S,4R)-4-benzyl-5-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-hydroxy-5-oxopentyl}-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate
• 英文别名: tert-butyl (3S)-4-[(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]-3-(2,2,2-trifluoroethylcarbamoyl)piperazine-1-carboxylate
• CAS: 342600-52-6
• 化学式: C₃₆H₄₇F₃N₄O₇
• 分子量: 704.787
• InChiKey: DLFJSEUSCUBMOD-HGBJMPHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  50
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-4-{(2S,4R)-4-benzyl-5-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-hydroxy-5-oxopentyl}-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate 在 盐酸 、 溶剂黄146 作用下， 以 醋酸异丙酯 、 N,N-二甲基甲酰胺-d7 为溶剂， 反应 52.0h， 生成 (2R,4S)-2-benzyl-5-[(5S)-2-[5-(5-chloropyridin-2-yl)-2-furyl]-4-oxo-3-(2,2,2-trifluoroethyl)-1,3,6-triazabicyclo[3.3.1]non-6-yl]-N-[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]-4-hydroxypentanamide
  参考文献：
  名称：

  Total synthesis of a second generation HIV protease inhibitor

  摘要：

  An efficient stereoselective preparation of HIV protease inhibitor (+)-1 was synthesized on multi-kilogram scale in 16 steps without the use of chromatography. The key steps include the diastereoselective alkylation of acetal 3, a diastereoselective iodo-hydroxylation to generate epoxide 6, and a reductive amination in the final coupling step that averts a non-productive Cyclic aminal intermediate. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.09.023
• 作为产物：
  描述：

  cis-4-amino-3-chromanol 在 甲烷磺酸 、 sodium methylate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 醋酸异丙酯 为溶剂， 反应 67.0h， 生成 tert-butyl (3S)-4-{(2S,4R)-4-benzyl-5-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-hydroxy-5-oxopentyl}-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate
  参考文献：
  名称：

  Total synthesis of a second generation HIV protease inhibitor

  摘要：

  An efficient stereoselective preparation of HIV protease inhibitor (+)-1 was synthesized on multi-kilogram scale in 16 steps without the use of chromatography. The key steps include the diastereoselective alkylation of acetal 3, a diastereoselective iodo-hydroxylation to generate epoxide 6, and a reductive amination in the final coupling step that averts a non-productive Cyclic aminal intermediate. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.09.023

文献信息

• Gamma-hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides and uses thereof
  申请人：Merck & Co., Inc.

  公开号：US06642237B1

  公开（公告）日：2003-11-04

  &ggr;-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds are inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.

  -Hydroxy-2-(氟烷基氨基甲酰)-1-哌嗪戊二酰胺化合物是HIV蛋白酶的抑制剂，也是HIV复制的抑制剂。这些化合物在预防或治疗HV感染以及治疗艾滋病方面非常有用，无论是作为化合物、药学上可接受的盐、药物组成成分，还是与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。这些化合物对目前用于治疗艾滋病和HIV感染的HIV蛋白酶抑制剂产生耐药性的HIV病毒突变体具有有效作用。
• 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
• Total synthesis of a second generation HIV protease inhibitor
  作者：Donald R. Gauthier、Norihiro Ikemoto、Fred J. Fleitz、Ronald H. Szumigala、Dan Petrillo、Jinchu Liu、Robert A. Reamer、Joseph D. Armstrong、Peter M. Yehl、Naijun Wu、R.P. Volante

  DOI：10.1016/j.tetasy.2003.09.023

  日期：2003.11

  An efficient stereoselective preparation of HIV protease inhibitor (+)-1 was synthesized on multi-kilogram scale in 16 steps without the use of chromatography. The key steps include the diastereoselective alkylation of acetal 3, a diastereoselective iodo-hydroxylation to generate epoxide 6, and a reductive amination in the final coupling step that averts a non-productive Cyclic aminal intermediate. (C) 2003 Elsevier Ltd. All rights reserved.