3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester | 348622-94-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester
• 英文别名: 2-diethoxyphosphoryl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid
• CAS: 348622-94-6
• 化学式: C₁₂H₂₃O₇P
• 分子量: 310.284
• InChiKey: QZHKYOPXQSFVRT-UHFFFAOYSA-N

物化性质

• 熔点：
  120-122 °C
• 沸点：
  431.8±40.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester 在 ((-)-(1S)-[1,1'-binaphthalene]-2,2'-diylbis[diphenylphosphine-κP])chloro[(1,2,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]ruthenium(1+) chloride 、 potassium tert-butylate 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 柠檬酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 叔丁醇 为溶剂， -5.0~60.0 ℃ 、413.7 kPa 条件下， 反应 79.0h， 生成 tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoate
  参考文献：
  名称：

  Asymmetric Synthesis of an MMP-3 Inhibitor Incorporating a 2-Alkyl Succinate Motif

  摘要：

  An efficient and practical synthesis is presented of the pharmaceutically active MMP-3 inhibitor UK-370,106 (1) via an olefination/catalytic asymmetric hydrogenation sequence. Commercially available 5-bromo-2-iodotoluene was converted in two steps to the biarylpropanal equivalent (11), which was reacted with the phosphonosuccinate (10) to selectively afford the trans-b-substituted itaconate (12). Catalytic asymmetric hydrogenation of the itaconate (12) was achieved in good conversion and with 86-96% enantiomeric excess with a range of phosphine-modified rhodium and ruthenium cationic complexes. The resulting enantiomerically enriched 2-alkyl succinate (2) was elaborated to the desired drug substance (1) in two steps. The synthesis benefits from several crystalline intermediates, allowing control of process impurities, and can be operated safely within parameters readily achievable on scale. Investigations into the polymorphic forms of (1) have shown that the compound crystallizes in planar sheets, based on a backbone of hydrogen-bonding amide and acid functionalities, with large hydrophobic pockets formed by the biarylpropyl groups. An understanding of this crystal-packing arrangement has aided the development of crystallization processes allowing complete control over solid form.

  DOI：

  10.1021/op034001y
• 作为产物：
  描述：

  1-乙基4-(叔-丁基)2-(二乙基膦酰)琥珀酸盐 在 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 18.0h， 以10 kg的产率得到3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester
  参考文献：
  名称：

  Asymmetric Synthesis of an MMP-3 Inhibitor Incorporating a 2-Alkyl Succinate Motif

  摘要：

  An efficient and practical synthesis is presented of the pharmaceutically active MMP-3 inhibitor UK-370,106 (1) via an olefination/catalytic asymmetric hydrogenation sequence. Commercially available 5-bromo-2-iodotoluene was converted in two steps to the biarylpropanal equivalent (11), which was reacted with the phosphonosuccinate (10) to selectively afford the trans-b-substituted itaconate (12). Catalytic asymmetric hydrogenation of the itaconate (12) was achieved in good conversion and with 86-96% enantiomeric excess with a range of phosphine-modified rhodium and ruthenium cationic complexes. The resulting enantiomerically enriched 2-alkyl succinate (2) was elaborated to the desired drug substance (1) in two steps. The synthesis benefits from several crystalline intermediates, allowing control of process impurities, and can be operated safely within parameters readily achievable on scale. Investigations into the polymorphic forms of (1) have shown that the compound crystallizes in planar sheets, based on a backbone of hydrogen-bonding amide and acid functionalities, with large hydrophobic pockets formed by the biarylpropyl groups. An understanding of this crystal-packing arrangement has aided the development of crystallization processes allowing complete control over solid form.

  DOI：

  10.1021/op034001y

文献信息

• 3-heterocyclylpropanohydroxamic acid PCP inhibitors
  申请人：——

  公开号：US20030069291A1

  公开（公告）日：2003-04-10

  Compounds of formula (I): 1 and their salts, solvates, hydrates and prodrugs are useful PCP inhibitors, processes for making the same, compositions comprising the same, and methods of treating a PCP-mediated condition or disease using the same.

  式(I)的化合物及其盐、溶剂合物、水合物和前药是有用的PCP抑制剂，制备这些化合物的方法，包含这些化合物的组合物，以及使用这些化合物治疗PCP介导的疾病或病症的方法。
• 3-ox(adi) azolylpropanohydroxamic acids useful as procollagen C- Proteinase inhibitors
  申请人：——

  公开号：US20020151535A1

  公开（公告）日：2002-10-17

  Compounds of formula (I): 1 wherein the substituents are as defined herein, and their salt, solvates, and prodrugs are procollagen C-proteinase (PCP) inhibitors useful in treating conditions mediated by PCP.

  式（I）的化合物： 其中取代基如本文所定义，并且它们的盐、溶剂合物和前药是用于治疗由PCP介导的疾病的前胶原C蛋白酶（PCP）抑制剂。
• Novel olefination process to itaconate and succinate derivatives
  申请人：——

  公开号：US20020058832A1

  公开（公告）日：2002-05-16

  An efficient and selective process, capable of scale-up, to make itaconate derivatives of formula (IV), and/or succinate derivatives of formula (V) and/or (VI) by asymmetric hydrogenation of the itaconate derivatives. 1

  一种高效且选择性的工艺，可扩大规模，通过对顺丁烯二酸衍生物进行不对称加氢，制备化学式（IV）的顺丁烯二酸衍生物，以及/或化学式（V）和/或（VI）的琥珀酸衍生物。
• Procollagen C-proteinase inhibitors
  申请人：——

  公开号：US20010021718A1

  公开（公告）日：2001-09-13

  1 and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.

  它们及其盐、溶剂合物、前药等，其中取代基具有此处提及的值，是Procollagen C-蛋白酶（PCP）抑制剂，并在由PCP介导的疾病中具有用途。
• [EN] OX(ADI)AZOLYL-HYDROXAMIC ACIDS USEFUL AS PROCOLLAGEN C-PROTEINASE INHIBITORS<br/>[FR] ACIDES OX(ADI)AZOLYL-HYDROXAMIQUES UTILISES COMME INHIBITEURS DE LA PROCOLLAGENE C-PROTEINASE
  申请人：PFIZER LTD

  公开号：WO2001047901A1

  公开（公告）日：2001-07-05

  Compounds of formula (I) and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.

  式(I)化合物及其盐、溶剂化物、前药等，其中取代基具有此处提及的值，是前胶原C-蛋白酶（PCP）抑制剂，在由PCP介导的疾病中具有应用价值。