methyl (5R)-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-(2-phenylethyl)-5-[(4-phenylphenoxy)methoxy]octanoate | 215317-17-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: methyl (5R)-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-(2-phenylethyl)-5-[(4-phenylphenoxy)methoxy]octanoate
• CAS: 215317-17-2
• 化学式: C₃₉H₄₅NO₇
• 分子量: 639.789
• InChiKey: JTDXSNGBXBTUKS-WPYCUTCCSA-N

物化性质

• 沸点：
  757.0±60.0 °C(Predicted)
• 密度：
  1.159±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  47
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (5R)-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-(2-phenylethyl)-5-[(4-phenylphenoxy)methoxy]octanoate 在 palladium on activated charcoal sodium hydroxide 、 florisil 、 硫酸 、 氢气 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， -30.0~25.0 ℃ 、344.73 kPa 条件下， 反应 132.0h， 生成 替拉那韦
  参考文献：
  名称：

  A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

  摘要：

  PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.

  DOI：

  10.1021/jo9809229
• 作为产物：
  描述：

  (R)-(4-苯基苯氧基)甲基-3-(2-苯基乙基)-3-[(4-苯基苯氧基)甲氧基]己酸酯 在 sodium hypochlorite 、 阻聚剂701 、 sodium hexamethyldisilazane 、 二异丁基氢化铝 、 碳酸氢钠 、 potassium bromide 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 1.0h， 生成 methyl (5R)-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-(2-phenylethyl)-5-[(4-phenylphenoxy)methoxy]octanoate
  参考文献：
  名称：

  A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

  摘要：

  PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.

  DOI：

  10.1021/jo9809229

文献信息

• [EN] PROCESS TO PRODUCE 4-HYDROXY-2-OXO-PYRANE DERIVATES USEFUL AS PROTEASE INHIBITORS<br/>[FR] PROCEDE DE PRODUCTION DE DERIVES DE 4-HYDROXY-2-OXO-PYRANE UTILES EN TANT QU'INHIBITEURS DE PROTEASE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1999012919A1

  公开（公告）日：1999-03-18

  (EN) Disclosed is a novel process and novel intermediates to prepare [R-(R*,R*) ]-N-[3-[1-[5, 6-dihydro-4-hydroxy -2-oxo-6-(2-phenylethyl) -6-propyl-2H-pyran-3- yl]propyl]phenyl]-5- (trifluoromethyl)-2- pyridinesulfonamide (XIX) which is a protease inhibitor useful in treating humans infected with the HIV virus.(FR) L'invention concerne un nouveau procédé de préparation et de nouveaux produits intermédiaires permettant de préparer [R-(R*,R*) ]-N-[3-[1-[5, 6-dihydro-4-hydroxy -2-oxo-6-(2-phényléthyl) -6-propyl-2H-pyran-3- yl]propyl]phényl]-5- (trifluorométhyl)-2- pyridinesulfonamide (XIX), qui est un inhibiteur de protéase utile pour traiter les humains atteints du virus VIH.

  揭示了一种新的工艺和新的中间体，用于制备[R-(R*,R*)]-N-[3-[1-[5,6-二氢-4-羟基-2-氧代-6-(2-苯乙基)-6-丙基-2H-吡喃-3-基]丙基]苯基]-5-(三氟甲基)-2-吡啶磺酰胺(XIX)，该化合物是一种蛋白酶抑制剂，可用于治疗感染HIV病毒的人类。
• J. Org. Chem. 1998, 63, 7348-7356
  作者：

  DOI：——

  日期：——
• PROCESS TO PRODUCE 4-HYDROXY-2-OXO-PYRANE DERIVATIVES USEFUL AS PROTEASE INHIBITORS
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1015441A1

  公开（公告）日：2000-07-05
• DEUTERIUM-ENRICHED TIPRANAVIR
  申请人：Czarnik Anthony W.

  公开号：US20090062346A1

  公开（公告）日：2009-03-05

  The present application describes deuterium-enriched tipranavir, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
• A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690
  作者：Kristina S. Fors、James R. Gage、Richard F. Heier、Robert C. Kelly、William R. Perrault、Nancy Wicnienski

  DOI：10.1021/jo9809229

  日期：1998.10.1

  PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.