O,O-dimethyl-N,N-bis(2-chloroethyl)phosphoramidate | 82475-49-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: O,O-dimethyl-N,N-bis(2-chloroethyl)phosphoramidate
• 英文别名: Dimethyl N,N-bis(2-chloroethyl)phosphoramidate；Dimethyl bis(2-chloroethyl)phosphoramidate；2-chloro-N-(2-chloroethyl)-N-dimethoxyphosphorylethanamine
• CAS: 82475-49-8
• 化学式: C₆H₁₄Cl₂NO₃P
• 分子量: 250.062
• InChiKey: BRRKKAHIRNMUTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O,O-dimethyl-N,N-bis(2-chloroethyl)phosphoramidate 在 吡啶 作用下， 以80%的产率得到2-Methoxy-2-oxo-3-(2-chloroethyl)-1,3,2-oxazaphospholidine
  参考文献：
  名称：

  Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation

  摘要：

  Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy. The decomposition of those substrates in D2O and in D2O-pyridine-d(5) was studied to elucidate the mechanism of their alkylating reactivity. The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions. Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles. The first pathway deactivates the substrate with respect to the alkylating reactivity. Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.

  DOI：

  10.1021/jo00117a039
• 作为产物：
  描述：

  双(2-氯乙基)氨基磷酰二氯 、 lithium methanolate 在 二苯并-18-冠醚-6 作用下， 以 苯 为溶剂， 以75%的产率得到O,O-dimethyl-N,N-bis(2-chloroethyl)phosphoramidate
  参考文献：
  名称：

  N-和O-三有机硅烷化化合物作为新型潜在前药的合成，水解反应和抗癌性评估

  摘要：

  合成了与各种抗癌药有关的N-和O-三有机硅烷化化合物，作为潜在的抗癌前药进行评估。水解甲硅烷基化反应的1 H-NMR和UV动力学测量用于关联结构解掩蔽的相对速率与围绕硅反应中心的空间体积。苯丁酸氮芥的叔丁基二甲基甲硅烷基酯和诺氮芥子的许多O-三有机硅烷化的氨基甲酸酯衍生物对小鼠的P-388淋巴细胞白血病表现出显着的活性。

  DOI：

  10.1002/jps.2600710517

文献信息

• Teulade, Marie-Paule; Savignac, Philippe, Phosphorus and Sulfur and the Related Elements, 1984, vol. 21, p. 23 - 30
  作者：Teulade, Marie-Paule、Savignac, Philippe

  DOI：——

  日期：——
• Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation
  作者：Charlotte le Roux、Agnes M. Modro、Tomasz A. Modro

  DOI：10.1021/jo00117a039

  日期：1995.6

  Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy. The decomposition of those substrates in D2O and in D2O-pyridine-d(5) was studied to elucidate the mechanism of their alkylating reactivity. The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions. Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles. The first pathway deactivates the substrate with respect to the alkylating reactivity. Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.
• Synthesis, Hydrolytic Reactivity, and Anticancer Evaluation of N- and O-Triorganosilylated Compounds as New Types of Potential Prodrugs
  作者：Fang-Ting Chiu、Young Hwan Chang、Günay Ӧzkan、Gerald Zon、Kenneth C. Fichter、Lawrence R. Phillips

  DOI：10.1002/jps.2600710517

  日期：1982.5

  N- and O-Triorganosilylated compounds related to various anticancer agents were synthesized for evaluation as potential anticancer prodrugs. 1H-NMR and UV kinetic measurements of hydrolytic desilylation were used to correlate relative rates of structural unmasking with steric bulk about the silicon reaction center. The tert-butyldimethylsilyl ester of chlorambucil and a number of O- triorganosilylated

  合成了与各种抗癌药有关的N-和O-三有机硅烷化化合物，作为潜在的抗癌前药进行评估。水解甲硅烷基化反应的1 H-NMR和UV动力学测量用于关联结构解掩蔽的相对速率与围绕硅反应中心的空间体积。苯丁酸氮芥的叔丁基二甲基甲硅烷基酯和诺氮芥子的许多O-三有机硅烷化的氨基甲酸酯衍生物对小鼠的P-388淋巴细胞白血病表现出显着的活性。