(3S,4aS,8aS)-2-[(2R)-2-[(4S)-2-[3-羟基-2-甲基苯基]-4,5-二氢恶唑-4-基]-2-羟乙基]十氢异喹啉-3-甲酸叔丁酰胺 | 188936-07-4

• 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
• 中文名称: (3S,4aS,8aS)-2-[(2R)-2-[(4S)-2-[3-羟基-2-甲基苯基]-4,5-二氢恶唑-4-基]-2-羟乙基]十氢异喹啉-3-甲酸叔丁酰胺
• 中文别名: 奈非那韦恶唑杂质
• 英文名称: (3S,4aS,8aS)-N-tert-butyl-2-((R)-2-hydroxy-2-((S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)ethyl)-decahydroisoquinoline-3-carboxamide
• 英文别名: (3S,4aS,8aS)-2-{(2R)-2-[(4S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl]-2-hydroxyethyl}decahydroisoquinoline-3-carboxylic acid t-butylamide；(3S,4aS,8aS)-2-[(2R)-2-[(4S)-2-[3-Hydroxy-2-methylphenyl]-4,5-dihydrooxazol-4-yl]-2-hydroxyethyl]decahydroisoquinoline-3-carboxylic acid tert-butylamide；(3S,4aS,8aS)-N-tert-butyl-2-[(2R)-2-hydroxy-2-[(4S)-2-(3-hydroxy-2-methylphenyl)-4,5-dihydro-1,3-oxazol-4-yl]ethyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide
• CAS: 188936-07-4
• 化学式: C₂₆H₃₉N₃O₄
• 分子量: 457.613
• InChiKey: ZRYANTNFGRJTJS-ZEVUWQFRSA-N

物化性质

• 沸点：
  684.5±55.0 °C(Predicted)
• 密度：
  1.28

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  94.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4aS,8aS)-2-[(2R)-2-[(4S)-2-[3-羟基-2-甲基苯基]-4,5-二氢恶唑-4-基]-2-羟乙基]十氢异喹啉-3-甲酸叔丁酰胺 以 乙二醇 为溶剂， 反应 20.0h， 生成 [3-[[(2S,3S)-1-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-acetyloxy-4-phenylsulfanylbutan-2-yl]carbamoyl]-2-methylphenyl] acetate
  参考文献：
  名称：

  A Practical Synthesis of Nelfinavir, an HIV-Protease Inhibitor, Using a Novel Chiral C4 Building Block:  (5R,6S)-2,2-Dimethyl-5-hydroxy-1,3-dioxepan-6-ylammonium Acetate

  摘要：

  DOI：

  10.1021/jo981472n
• 作为产物：
  描述：

  3-乙酰氧基-2-甲基苯甲酰氯 在 三氟化硼乙醚 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 (3S,4aS,8aS)-2-[(2R)-2-[(4S)-2-[3-羟基-2-甲基苯基]-4,5-二氢恶唑-4-基]-2-羟乙基]十氢异喹啉-3-甲酸叔丁酰胺
  参考文献：
  名称：

  A Practical Synthesis of Nelfinavir, an HIV-Protease Inhibitor, Using a Novel Chiral C4 Building Block:  (5R,6S)-2,2-Dimethyl-5-hydroxy-1,3-dioxepan-6-ylammonium Acetate

  摘要：

  DOI：

  10.1021/jo981472n

文献信息

• Enantioselective Synthesis of Nelfinavir via Asymmetric Bromocyclization of Bisallylic Amide
  作者：Yoshihiro Nagao、Tatsunari Hisanaga、Takahiro Utsumi、Hiromichi Egami、Yuji Kawato、Yoshitaka Hamashima

  DOI：10.1021/acs.joc.8b00039

  日期：2018.7.6

  We describe a concise enantioselective synthesis of the HIV-protease inhibitor nelfinavir (1) via a new route in which the key step is construction of the central optically active 1,2-amino alcohol framework via asymmetric bromocyclization of bisallylic amide with N-bromosuccinimide in the presence of a catalytic amount of (S)-BINAP or (S)-BINAP monoxide. The remaining alkene and bromo functionalities

  我们通过一个新途径描述了一个简单的HIV蛋白酶抑制剂nelfinavir（1）的对映体选择性合成，其中关键步骤是通过N-溴代琥珀酰亚胺的不对称溴环化双烯丙基酰胺的中心旋光性1,2-氨基醇骨架的构建。催化量的（S）-BINAP或（S）-BINAP一氧化碳的存在。其余的烯烃和溴官能团分别用于安装必要的硫醚和手性过氢异喹啉单元。
• Process for producing amide derivatives and intermediates therefor
  申请人：Japan Tobacco Inc.

  公开号：US06133461A1

  公开（公告）日：2000-10-17

  A method for producing an amide derivative of the formula [XV] ##STR1## wherein each symbol is as defined in the specification, and an enantiomer thereof, a novel intermediate useful for producing said compound and a production method thereof. The production method of the present invention is extremely easy and simple as compared to the conventional methods, and enables effective production of compound [XV] at high yields, which includes compound [XVI] having an HIV protease inhibitory action. In addition, the novel intermediates of the present invention are extremely useful as intermediates for producing not only the aforementioned compound [XVI] but also compounds useful as X-ray contrast media.

  一种用于生产化合物[XV]的酰胺衍生物的方法，其中每个符号如规范中定义的，并且其对映体，一种有用于生产该化合物的新型中间体及其生产方法。本发明的生产方法与传统方法相比极为简单易行，并能够以高产率有效地生产化合物[XV]，其中包括具有HIV蛋白酶抑制作用的化合物[XVI]。此外，本发明的新型中间体对于生产不仅是前述化合物[XVI]，还有用作X射线对比介质的化合物而言极为有用。
• Production of amide derivatives and intermediates therefor
  申请人：——

  公开号：US20010021782A1

  公开（公告）日：2001-09-13

  A method for producing an amide derivative of the formula [XV] 1 wherein each symbol is as defined in the specification, and an enantiomer thereof, a novel intermediate useful for producing said compound and a production method thereof. The production method of the present invention is extremely easy and simple as compared to the conventional methods, and enables effective production of compound [XV] at high yields, which includes compound [XVI] having an HIV protease inhibitory action. In addition, the novel intermediates of the present invention are extremely useful as intermediates for producing not only the aforementioned compound [XVI] but also compounds useful as X-ray contrast media.

  一种生产式子[XV]1的酰胺衍生物及其对映体的方法，其中每个符号如规范中所定义，以及用于生产所述化合物的新型中间体及其生产方法。与传统方法相比，本发明的生产方法非常简单易行，并能够高产地有效地生产化合物[XV]，其中包括具有HIV蛋白酶抑制作用的化合物[XVI]。此外，本发明的新型中间体极为有用，不仅可用于生产上述化合物[XVI]，还可用于生产作为X射线造影剂的化合物。
• Methods for the preparation of intermediates in the synthesis of HIV-protease inhibitors
  申请人：——

  公开号：US20030023092A1

  公开（公告）日：2003-01-30

  Methods for the preparation of chemical intermediates in the synthesis of HIV-protease inhibitors related to and including nelfinavir mesylate are disclosed. The method of this invention comprises converting tetrohydran derivatives into oxazolines to provide key reaction intermediates for the preparation of nelfinavir. Also disclosed is a method for the preparation of a chiral amino alcohol from an epoxy-tetrahydrofuran.

  本发明揭示了在制备与包括奈非那韦甲磺酸盐相关的HIV蛋白酶抑制剂的化学中间体的方法。本发明的方法包括将四氢噻唑衍生物转化为噁唑啉，以提供制备奈非那韦的关键反应中间体。还揭示了一种从环氧四氢呋喃制备手性氨基醇的方法。
• Methods for producing amide derivative
  申请人：——

  公开号：US20030040633A1

  公开（公告）日：2003-02-27

  A method for producing an amide derivative of the formula [XV] 1 wherein each symbol is as defined in the specification, and an enantiomer thereof, a novel intermediate useful for producing said compound and a production method thereof. The production method of the present invention is extremely easy and simple as compared to the conventional methods, and enables effective production of compound [XV] at high yields, which includes compound [XVI] having an HIV protease inhibitory action. In addition, the novel intermediates of the present invention are extremely useful as intermediates for producing not only the aforementioned compound [XVI] but also compounds useful as X-ray contrast media.

  一种生产化合物[XV]1的酰胺衍生物及其对映异构体的方法，其中每个符号如规范中所定义，以及用于生产该化合物的一种新型中间体及其生产方法。与传统方法相比，本发明的生产方法非常简单易行，并能够高产地有效生产包括具有HIV蛋白酶抑制作用的化合物[XVI]在内的化合物[XV]。此外，本发明的新型中间体不仅极其有用，可用于生产上述化合物[XVI]，还可用于生产作为X射线造影剂的化合物。