4,5-bis(tert-butyldimethylsilyloxymethyl)-1-methyl-1H-imidazole | 200552-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4,5-bis(tert-butyldimethylsilyloxymethyl)-1-methyl-1H-imidazole
• 英文别名: Tert-butyl-[[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methylimidazol-4-yl]methoxy]-dimethylsilane
• CAS: 200552-04-1
• 化学式: C₁₈H₃₈N₂O₂Si₂
• 分子量: 370.683
• InChiKey: VFESEIHOTSJVHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.46
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-bis(tert-butyldimethylsilyloxymethyl)-1-methyl-1H-imidazole 在 正丁基锂 、 四丁基氟化铵 、 二乙酸二丁基锡 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (1-甲基-4-((((甲基氨基)羰基)氧基)甲基)-2-(甲硫基)-1H-咪唑-5-基)甲基甲基氨基甲酸酯盐酸盐
  参考文献：
  名称：

  A new synthesis of carmethizole and related nitrogen analogues

  摘要：

  A new efficient six-step synthesis of carmethizole, a novel bis-carbamate alkylating agent, and syntheses of related nitrogen analogues are described, using a key 4,5-disubstituted imidazole intermediate 8. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)10238-6
• 作为产物：
  描述：

  咪唑-4,5-二羧酸 在 咪唑 、 lithium aluminium tetrahydride 、 氯化亚砜 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 173.0h， 生成 4,5-bis(tert-butyldimethylsilyloxymethyl)-1-methyl-1H-imidazole
  参考文献：
  名称：

  Design, Synthesis and Evaluation of Imidazolylmethyl Carbamate Prodrugs of Alkylating Agents

  摘要：

  Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2-carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)01031-5

文献信息

• Design, Synthesis and Evaluation of Imidazolylmethyl Carbamate Prodrugs of Alkylating Agents
  作者：Michael P. Hay、William R. Wilson、William A. Denny

  DOI：10.1016/s0040-4020(99)01031-5

  日期：2000.1

  Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2-carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.
• A new synthesis of carmethizole and related nitrogen analogues
  作者：Michael P. Hay、William A. Denny

  DOI：10.1016/s0040-4039(97)10238-6

  日期：1997.12

  A new efficient six-step synthesis of carmethizole, a novel bis-carbamate alkylating agent, and syntheses of related nitrogen analogues are described, using a key 4,5-disubstituted imidazole intermediate 8. (C) 1997 Elsevier Science Ltd.