4-(3-chloro-4-fluoroanilino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine | 362509-18-0

• 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: 4-(3-chloro-4-fluoroanilino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine
• 英文别名: N-(3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-amine
• CAS: 362509-18-0
• 化学式: C₁₆H₁₃ClFN₃S
• 分子量: 333.817
• InChiKey: FMHIYAGUZGTJDC-UHFFFAOYSA-N

物化性质

• 熔点：
  135-137 °C
• 沸点：
  508.2±50.0 °C(predicted)
• 密度：
  1.460±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-4,5,6,7-四氢苯并噻酚-3-羧酸乙酯 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 0.75h， 生成 4-(3-chloro-4-fluoroanilino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine
  参考文献：
  名称：

  Novel Dual Use of Formamide-POCl₃ Mixture for the Efficient, One-Pot Synthesis of Condensed 2H-Pyrimidin-4-amine Libraries Under Microwave Irradiation

  摘要：

  The novel dual use of formamide-POCl3 mixture for the incorporation of a C-N fragment to form the pyrimidine nucleus and its subsequent chlorination in an efficient, one-pot synthesis of potentially bioactive condensed 2H-pyrimidin-4-amine libraries under microwave irradiation (MWI) is reported. The one-pot microwave-assisted synthetic protocol is high-yielding, ecofriendly, rapid, and novel as well as eliminates intermittent work-ups. The protocol can be adapted for the library synthesis of series of a condensed pyrimidines.

  DOI：

  10.1080/00397911.2011.607934

文献信息

• Microwave-based synthesis of novel thienopyrimidine bioisosteres of gefitinib
  作者：Manisha S. Phoujdar、Muthu K. Kathiravan、Jitender B. Bariwal、Anamik K. Shah、Kishor S. Jain

  DOI：10.1016/j.tetlet.2007.11.135

  日期：2008.2

  A series of novel 2-unsubstituted 4-(substituted)anilinothieno[2,3-d]pyrimidines is synthesized through the chlorination of the corresponding 2-unsubstituted-thieno[2,3-d]-pyrimidin-4-ones, followed by the nucleophilic displacement of the 4-Cl group of 9, with a variety of anilines. All four steps of this synthesis involve microwave irradiation (MWI) and the entire synthesis requires only 2 h. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors
  作者：Séverine Ravez、Stéphane Arsenlis、Amélie Barczyk、Anthony Dupont、Raphaël Frédérick、Stéphanie Hesse、Gilbert Kirsch、Patrick Depreux、Laurence Goossens

  DOI：10.1016/j.bmc.2015.10.035

  日期：2015.11

  Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmacological evaluation against nine kinases (EGFR, PDGFR-ss, c-Kit, c-Met, Src, Raf, VEGFR-1, -2 and -3). Most of the synthesized compounds showed from moderate to potent activities against c-Kit with IC50 values in the nanomolar range. Among them, 4-anilino(urea) thienopyrimidine analogs showed selectivity and potent c-Kit inhibition with IC50 values less than 6 nM. Docking simulation was performed for the most promising compound 9 into the c-Kit active site to determine the potential binding mode. This study reveal that the 4-anilino(urea) thienopyrimidine is an interesting scaffold to design novel potent and selective c-Kit inhibitors which may make promising candidates for cancers where c-Kit receptors are overexpressed. (C) 2015 Elsevier Ltd. All rights reserved.
• Novel Dual Use of Formamide-POCl₃ Mixture for the Efficient, One-Pot Synthesis of Condensed 2<i>H</i>-Pyrimidin-4-amine Libraries Under Microwave Irradiation
  作者：Kishore S. Jain、Muthu K. Kathiravan、Jitender B. Bariwal、Pratip K. Chaskar、Santosh S. Tompe、Nikhilesh Arya

  DOI：10.1080/00397911.2011.607934

  日期：2013.1.1

  The novel dual use of formamide-POCl3 mixture for the incorporation of a C-N fragment to form the pyrimidine nucleus and its subsequent chlorination in an efficient, one-pot synthesis of potentially bioactive condensed 2H-pyrimidin-4-amine libraries under microwave irradiation (MWI) is reported. The one-pot microwave-assisted synthetic protocol is high-yielding, ecofriendly, rapid, and novel as well as eliminates intermittent work-ups. The protocol can be adapted for the library synthesis of series of a condensed pyrimidines.