tert-butyl (3S)-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate | 342600-51-5

• 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)-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate
• 英文别名: (3S)-1-(tert-Butoxycarbonyl)-3beta-(2,2,2-trifluoroethylcarbamoyl)piperazine；tert-butyl (3S)-3-(2,2,2-trifluoroethylcarbamoyl)piperazine-1-carboxylate
• CAS: 342600-51-5
• 化学式: C₁₂H₂₀F₃N₃O₃
• 分子量: 311.304
• InChiKey: BDZVMARPQLXNIY-QMMMGPOBSA-N

物化性质

• 沸点：
  410.7±45.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-3-{[(2,2,2-trifluoroethyl)amino]carbonyl}piperazine-1-carboxylate 在 咪唑 、 盐酸 、 lithium hydroxide 、 水 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 46.6h， 生成 (αR,γS,2S)-4-(2-benzopyranylmethyl)-N-((3S,4S)-3,4-dihydro-3-hydroxy-2H-1-benzopyran-4-yl)-γ-hydroxy-α-(3-pyridinylmethyl)-2-[[(2,2,2-trifluoroethyl)amino]carbonyl]-1-piperazinepentanamide
  参考文献：
  名称：

  HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent

  摘要：

  Transposition of the pyridyl nitrogen from the P-3 substituent to the P-1' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00680-2
• 作为产物：
  描述：

  2-甲酸吡嗪 在 palladium dihydroxide 氢气 、 1-羟基苯并三唑 、 (+)-10-camphorsulfonic acid 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 醋酸异丙酯 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 10.0~73.0 ℃ 、275.79 kPa 条件下， 反应 12.5h， 生成 tert-butyl (3S)-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

• 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors
  申请人：American Home Products Corporation

  公开号：US20020026052A1

  公开（公告）日：2002-02-28

  This invention provides compounds of Formula (I), having the structure 1 where T, Z, X, A, R 1 , R 2a , R 2b , R 2c , R 3 , R 4 , and n are defined herein, or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of osteoporosis and polycystic kidney disease.

  这项发明提供了具有结构的化合物（I）的公式， 其中T、Z、X、A、R 1 、R 2a 、R 2b 、R 2c 、R 3 、R 4 和n在此处定义，或其药学上可接受的盐，这些化合物可用作抗肿瘤药物，并用于骨质疏松症和多囊肾病的治疗。
• 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。
• 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。
• [EN] HIV PROTEASE INHIBITORS SUPPORTED ON CATION EXCHANGE RESINS FOR ORAL ADMINISTRATION<br/>[FR] INHIBITEURS DE LA PROTEASE VIH RETENUS SUR DES SUPPORTS EN RESINES D'ECHANGE DE CATIONS DESTINES A L'ADMINISTRATION PAR VOIE ORALE
  申请人：MERCK & CO INC

  公开号：WO2002067683A1

  公开（公告）日：2002-09-06

  γ-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds useful for inhibiting HIV protease and HIV replication and useful in the prevention or treatment of infection by HIV and the treatment of AIDS are complexed with cation exchange resins for oral administration.

  γ-羟基-2-（氟烷基氨基甲酰基）-1-哌嗪戊酰胺化合物可用于抑制HIV蛋白酶和HIV复制，并用于预防或治疗HIV感染和治疗艾滋病，与阳离子交换树脂形成复合物，以进行口服给药。
• [EN] 3-CYANOQUINOLINES,3-CYANO-1,6-NAPHTHYRIDINES, AND 3-CYANO-1,7-NAPHTHYRIDINES AS PROTEIN KINASE INHIBITORS<br/>[FR] 3-CYANOQUINOLINES,3-CYANO-1,6-NAPHTHYRIDINES ET 3-CYANO-1,7-NAPHTHYRIDINES UTILISEES COMME INHIBITEURS DE PROTEINEKINASE
  申请人：AMERICAN HOME PROD

  公开号：WO2001072711A1

  公开（公告）日：2001-10-04

  Compounds of Formula (I), having the structure or a pharmaceutically salt thereof are useful as antineoplastic agents and in the treatment of osteoporosis and polycystic kidney disease.

  具有结构式（I）或其药物盐的化合物在抗肿瘤药物和治疗骨质疏松症和多囊肾病方面是有用的。