ethyl (2-bromoethyl)-N-methylcarbamate | 99548-19-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (2-bromoethyl)-N-methylcarbamate
• 英文别名: ethyl 2-bromoethyl(methyl)carbamate；ethyl N-(2-bromoethyl)-N-methylcarbamate
• CAS: 99548-19-3
• 化学式: C₆H₁₂BrNO₂
• 分子量: 210.071
• InChiKey: DYKKBWHVNPOLIO-UHFFFAOYSA-N

物化性质

• 沸点：
  218.4±19.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl (2-bromoethyl)-N-methylcarbamate 、 6,7-dihydro-8-phenyl-9-<4-<2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy>phenyl>-5H-benzocyclohepten-3-ol 在 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 16.0h， 以11%的产率得到ethyl N-methyl-(2-((8-phenyl-9-(4-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)phenyl)-6,7-dihydro-5H-benzocyclohepten-3-yl)oxy)ethyl)carbamate
  参考文献：
  名称：

  Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells

  摘要：

  Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.

  DOI：

  10.1021/jm500569h
• 作为产物：
  描述：

  N-ethoxycarbonyl-N-methyl-2-aminoethanol 在 四溴化碳 、 三苯基膦 作用下， 以 乙醚 为溶剂， 反应 6.0h， 以91%的产率得到ethyl (2-bromoethyl)-N-methylcarbamate
  参考文献：
  名称：

  A convenient synthesis of (Z)-4-hydroxy-N-desmethyltamoxifen (endoxifen)

  摘要：

  A mixture of the (Z)- and (E)-isomers of 4-hydroxy-N-desmethyltamoxifen was conveniently prepared in four steps. These geometrical isomers were then neatly separated by semi-preparative Reverse Phase High Performance Liquid Chromatography (RP-HPLC) using specified conditions. Additionally, the isolated E-isomer could be equilibrated in aqueous strong acid in acetonitrile or trifluoroacetic acid/dichloromethane to give a clean 1: 1 mixture of Z/E isomers that was re-subjected to HPLC separation. In this way, most of the undesired (E)-isomer could be readily converted to the desired (Z)-isomer providing quick access to over 200 mg quantities of pure endoxifen (Z-isomer), a potent antiestrogenic metabolite of tamoxifen traditionally used in breast cancer treatment. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.117

文献信息

• A convenient synthesis of (Z)-4-hydroxy-N-desmethyltamoxifen (endoxifen)
  作者：Abdul H. Fauq、Ghulam M. Maharvi、Dola Sinha

  DOI：10.1016/j.bmcl.2010.03.117

  日期：2010.5

  A mixture of the (Z)- and (E)-isomers of 4-hydroxy-N-desmethyltamoxifen was conveniently prepared in four steps. These geometrical isomers were then neatly separated by semi-preparative Reverse Phase High Performance Liquid Chromatography (RP-HPLC) using specified conditions. Additionally, the isolated E-isomer could be equilibrated in aqueous strong acid in acetonitrile or trifluoroacetic acid/dichloromethane to give a clean 1: 1 mixture of Z/E isomers that was re-subjected to HPLC separation. In this way, most of the undesired (E)-isomer could be readily converted to the desired (Z)-isomer providing quick access to over 200 mg quantities of pure endoxifen (Z-isomer), a potent antiestrogenic metabolite of tamoxifen traditionally used in breast cancer treatment. (C) 2010 Elsevier Ltd. All rights reserved.
• Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells
  作者：Philipp Y. Maximov、Daphne J. Fernandes、Russell E. McDaniel、Cynthia B. Myers、Ramona F. Curpan、V. Craig Jordan

  DOI：10.1021/jm500569h

  日期：2014.6.12

  Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.