2-[3-(3-chloro-4-fluoro-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol | 607716-58-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[3-(3-chloro-4-fluoro-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol
• 英文别名: 2-[3-(3-Chloro-4-fluorophenyl)imidazo[1,2-alpha]pyrimidin-7-yl]propan-2-ol；2-[3-(3-chloro-4-fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl]propan-2-ol
• CAS: 607716-58-5
• 化学式: C₁₅H₁₃ClFN₃O
• 分子量: 305.739
• InChiKey: HFPZPAJCFRHGRR-UHFFFAOYSA-N

物化性质

• 熔点：
  180-182 °C
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-(3-chloro-4-fluoro-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol 、 3-吡啶硼酸 在 三叔丁基膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ potassium phosphate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 生成 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o
• 作为产物：
  描述：

  3-羟基-3-甲基-2-丁酮 在 palladium diacetate 、 三苯基膦 4-二甲氨基吡啶 、 乙醇 、 三氟化硼乙醚 、 sodium methylate 、 caesium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 42.45h， 生成 2-[3-(3-chloro-4-fluoro-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o

文献信息

• Imidazo-pyrimidine derivatives as ligands for gaba receptors
  申请人：——

  公开号：US20020193385A1

  公开（公告）日：2002-12-19

  A class of 3-phenylimidazo[1,2-&agr;]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABA A receptors, in particular having good affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑[1,2-&agr;]嘧啶衍生物，苯环的间位被取代，取代基可以是直接连接或通过氧原子或-NH-键桥接的取代芳基或杂环芳基，苯环上进一步被取代为烷基，三氟甲基，烷氧基或一个或两个卤素原子，特别是氟，是GABAA受体的选择性配体，特别是对其中的&agr;2和/或&agr;3和/或&agr;5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑，惊厥和认知障碍具有益处。
• Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach
  作者：Mark S. Jensen、R. Scott Hoerrner、Wenjie Li、Dorian P. Nelson、Gary J. Javadi、Peter G. Dormer、Dongwei Cai、Robert D. Larsen

  DOI：10.1021/jo050741o

  日期：2005.7.1

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.