benzyl N,N-bis(2-chloroethyl)phosphoramidochloridate | 82576-66-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: benzyl N,N-bis(2-chloroethyl)phosphoramidochloridate
• 英文别名: 2-chloro-N-(2-chloroethyl)-N-[chloro(phenylmethoxy)phosphoryl]ethanamine
• CAS: 82576-66-7
• 化学式: C₁₁H₁₅Cl₃NO₂P
• 分子量: 330.578
• InChiKey: SDDFMJIFRVTWQT-UHFFFAOYSA-N

物化性质

• 沸点：
  410.2±55.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl N,N-bis(2-chloroethyl)phosphoramidochloridate 在 sodium hydroxide 、 sodium tungstate 、 双氧水 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 172.0h， 生成 benzyl N,N-bis(2-chloroethyl)-N'-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)phosphorodiamidate
  参考文献：
  名称：

  Synthesis and study of a spin-labeled cyclophosphamide analog 3-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide

  摘要：

  3-(1-Oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (7) was isolated in 36% yield following H2O2-Na2WO4 oxidation of 3-(2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (6), which was synthesized in three steps (25% yield) starting with 4-amino-2,2,6,6-tetramethylpiperidine. Binding of 7 to mouse liver microsomes was investigated by optical and electron spin resonance spectroscopy. Compared with the mouse liver microsomal metabolism of 1, separate incubations of 6 and an ca. 1:1 mixture of 1 and 6 gave approximately 90 and 60% less acrolein, respectively. A spin-labeled metabolite of 7, viz., N-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)phosphoramide mustard (9), was synthesized and its intramolecular O-alkylation at pH 7.4, 37 degrees C, was studied by 31P NMR spectroscopy. Compounds 7 and 9 were inactive in screening tests against L1210 lymphoid leukemia in mice.

  DOI：

  10.1021/jm00351a021
• 作为产物：
  描述：

  双(2-氯乙基)氨基磷酰二氯 、 苯甲醇钠 以 苯 为溶剂， 反应 2.0h， 生成 benzyl N,N-bis(2-chloroethyl)phosphoramidochloridate
  参考文献：
  名称：

  Synthesis and study of a spin-labeled cyclophosphamide analog 3-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide

  摘要：

  3-(1-Oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (7) was isolated in 36% yield following H2O2-Na2WO4 oxidation of 3-(2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (6), which was synthesized in three steps (25% yield) starting with 4-amino-2,2,6,6-tetramethylpiperidine. Binding of 7 to mouse liver microsomes was investigated by optical and electron spin resonance spectroscopy. Compared with the mouse liver microsomal metabolism of 1, separate incubations of 6 and an ca. 1:1 mixture of 1 and 6 gave approximately 90 and 60% less acrolein, respectively. A spin-labeled metabolite of 7, viz., N-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)phosphoramide mustard (9), was synthesized and its intramolecular O-alkylation at pH 7.4, 37 degrees C, was studied by 31P NMR spectroscopy. Compounds 7 and 9 were inactive in screening tests against L1210 lymphoid leukemia in mice.

  DOI：

  10.1021/jm00351a021

文献信息

• Chemically stable, lipophilic prodrugs of phosphoramide mustard as potential anticancer agents
  作者：Chul Hoon Kwon、Ki Young Moon、Nesrine Baturay、Frances N. Shirota

  DOI：10.1021/jm00106a018

  日期：1991.2

  and methyl phosphoramide mustard (5) were examined as lipophilic, chemically stable prodrugs of phosphoramide mustard (2). These phosphorodiamidic esters are designed to undergo biotransformation by hepatic microsomal enzymes to produce 2. The rate of formation of alkylating species, viz., 2, from these prodrugs and their in vitro cytotoxicity toward mouse embryo Balb/c 3T3 cells were comparable to

  研究了苄基磷酰胺芥末（3），2,4-二氟苄基磷酰胺芥末（4）和甲基磷酰胺芥末（5）作为磷酰胺芥末（2）的亲脂性，化学稳定性的前药。这些磷酸二酰胺酯经设计可通过肝微粒体酶进行生物转化，生成2。从这些前药形成的烷基化物质（即2）的形成速率及其对小鼠胚胎Balb / c 3T3细胞的体外细胞毒性可比或更高比环磷酰胺（1）然而，针对小鼠中的L1210白血病的初步抗肿瘤筛选表明，这些前药在体内没有任何明显的抗肿瘤活性。
• Synthesis of N-Phosphorylated Derivatives of Nitrogen Mustards with Latent Cytotoxicity¹
  作者：Orrie M. Friedman、Eliahu Boger、Vytautas Grubliauskas、Harold Sommer

  DOI：10.1021/jm00337a012

  日期：1963.1
• Phosphorus-31 NMR kinetic studies of the intra- and intermolecular alkylation chemistry of phosphoramide mustard and cognate N-phosphorylated derivatives of N,N-bis(2-chloroethyl)amine
  作者：Thomas W. Engle、Gerald Zon、William Egan

  DOI：10.1021/jm00353a015

  日期：1982.11
• Synthesis and study of a spin-labeled cyclophosphamide analog 3-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide
  作者：Fai Po Tsui、Frank A. Robey、Thomas W. Engle、Susan Marie Ludeman、Gerald Zon

  DOI：10.1021/jm00351a021

  日期：1982.9

  3-(1-Oxy-2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (7) was isolated in 36% yield following H2O2-Na2WO4 oxidation of 3-(2,2,6,6-tetramethyl-4-piperidinyl)cyclophosphamide (6), which was synthesized in three steps (25% yield) starting with 4-amino-2,2,6,6-tetramethylpiperidine. Binding of 7 to mouse liver microsomes was investigated by optical and electron spin resonance spectroscopy. Compared with the mouse liver microsomal metabolism of 1, separate incubations of 6 and an ca. 1:1 mixture of 1 and 6 gave approximately 90 and 60% less acrolein, respectively. A spin-labeled metabolite of 7, viz., N-(1-oxy-2,2,6,6-tetramethyl-4-piperidinyl)phosphoramide mustard (9), was synthesized and its intramolecular O-alkylation at pH 7.4, 37 degrees C, was studied by 31P NMR spectroscopy. Compounds 7 and 9 were inactive in screening tests against L1210 lymphoid leukemia in mice.