tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-(ethylcarbamoyloxy)pyrrolidine-1-carboxylate | 833473-61-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-(ethylcarbamoyloxy)pyrrolidine-1-carboxylate
• CAS: 833473-61-3
• 化学式: C₃₃H₃₃ClFN₅O₅S
• 分子量: 666.173
• InChiKey: VCWMRHIIHXILMF-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-(ethylcarbamoyloxy)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到(3R,5S)-5-{2-[4-({3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)thieno[3,2-d]pyrimidin-6-yl]ethynyl}pyrrolidin-3-yl N-ethylcarbamate
  参考文献：
  名称：

  Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  摘要：

  A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.023
• 作为产物：
  描述：

  tert-butyl (2S,4R)-4-(ethylcarbamoyloxy)-2-ethynylpyrrolidine-1-carboxylate 、 6-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺 在 copper(l) iodide 、 dichlorobis[benzyldiphenylphosphine]palladium(II) 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-(ethylcarbamoyloxy)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

  摘要：

  A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d] pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modi. cation of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.090