1-(5-fluoropyridin-2-yl)ethyl 4-methylbenzene sulfonate | 1345973-16-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(5-fluoropyridin-2-yl)ethyl 4-methylbenzene sulfonate
• 英文别名: 1-(5-Fluoropyridin-2-yl)ethyl 4-methylbenzenesulfonate；1-(5-fluoropyridin-2-yl)ethyl 4-methylbenzenesulfonate
• CAS: 1345973-16-1
• 化学式: C₁₄H₁₄FNO₃S
• 分子量: 295.334
• InChiKey: VRSLNWNZLVDWJC-UHFFFAOYSA-N

物化性质

• 沸点：
  412.4±40.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5-fluoropyridin-2-yl)ethyl 4-methylbenzene sulfonate 在 盐酸 、 甲醇 、 manganese(IV) oxide 、 sodium chlorite 、 potassium phosphate 、 sodium dihydrogenphosphate 、 copper(l) iodide 、 2-甲基-2-丁烯 、 四丁基氟化铵 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 trans-1,2-cyclohexanediamine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 81.5h， 生成 (6-(1-(5-fluoropyridin-2-yl)ethoxy)-1-(3-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)((2R)-2-methylmorpholin-4-yl)-methanone
  参考文献：
  名称：

  Discovery of Potent, Selective, and Brain-Penetrant 1H-Pyrazol-5-yl-1H-pyrrolo[2,3-b]pyridines as Anaplastic Lymphoma Kinase (ALK) Inhibitors

  摘要：

  Anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, is predominantly expressed in the brain and implicated in neuronal development and cognition. However, the detailed function of ALK in the central nervous system (CNS) is still unclear. To elucidate the role of ALK in the CNS, it was necessary to discover a potent, selective, and brain-penetrant ALK inhibitor. Scaffold hopping and lead optimization of N-(2,4-difluorobenzyl)-3-(1H-pyrazol-5yl)imidazo[1,2-b]pyridazin-6-amine 1 guided by a cocrystal structure of compound 1 bound to ALK resulted in the identification of (6-(1-(5-fluoropyridin-2-yl)ethoxy)-1-(5-methyl-1H-pyrazol-3-yl)-1H-pyrrolo [2,3-b)]pyridin-3-yl) ( (2S)-2-methylmorpholin-4-yl)methanone 13 as a highly potent, selective, and brain-penetrable compound. Intraperitoneal administration of compound 13 significantly decreased the phosphorylated-ALK (p-ALK) levels in the hippocampus and prefrontal cortex in the mouse brain. These results suggest that compound 13 could serve as a useful chemical probe to elucidate the mechanism of ALK-mediated brain functions and the therapeutic potential of ALK inhibition.

  DOI：

  10.1021/acs.jmedchem.8b01630
• 作为产物：
  描述：

  2-溴-5-氟吡啶 在 4-二甲氨基吡啶 、 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 1-(5-fluoropyridin-2-yl)ethyl 4-methylbenzene sulfonate
  参考文献：
  名称：

  [EN] NOVEL SPIROPIPERIDINE PROLYLCARBOXYPEPTIDASE INHIBITORS
  [FR] NOUVEAUX INHIBITEURS DE SPIROPIPÉRIDINE PROLYLCARBOXYPEPTIDASE

  摘要：

  结构式（I）化合物是脯氨酰羧肽酶（PrCP）的抑制剂。本发明的化合物对于预防和治疗与PrCP酶活性相关的疾病非常有用，如异常代谢，包括肥胖、糖尿病、代谢综合征、肥胖相关疾病和糖尿病相关疾病。

  公开号：

  WO2011137024A1

文献信息

• Scalable Synthesis of Trifluoromethylated Imidazo-Fused N-Heterocycles Using TFAA and Trifluoroacetamide as CF₃-Reagents
  作者：Gabriel Schäfer、Muhamed Ahmetovic、Stefan Abele

  DOI：10.1021/acs.orglett.7b03291

  日期：2017.12.15

  A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic N-trifluoroacetamides followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the preparation of benzylic N-trifluoroacetamides via

  提出了使用TFAA作为三氟甲基化试剂从杂环苄胺可扩展合成三氟甲基化的咪唑并稠合的N-杂环。反应通过中间体苄基N-三氟乙酰胺进行，然后脱水环化为产物。为了进一步拓宽范围和实用性，开发了通过三氟乙酰胺与苄基（伪）卤化物的烷基化制备苄基N-三氟乙酰胺的新方法。两种方法都在温和的条件下进行，并且它们的共生提供了广泛的新型CF 3-杂环的途径。
• NOVEL SPIROPIPERIDINE PROLYLCARBOXYPEPTIDASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2563764B1

  公开（公告）日：2015-02-25
• US8785634B2
  申请人：——

  公开号：US8785634B2

  公开（公告）日：2014-07-22
• [EN] NOVEL SPIROPIPERIDINE PROLYLCARBOXYPEPTIDASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE SPIROPIPÉRIDINE PROLYLCARBOXYPEPTIDASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011137024A1

  公开（公告）日：2011-11-03

  Compounds of structural formula (I) are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

  结构式（I）化合物是脯氨酰羧肽酶（PrCP）的抑制剂。本发明的化合物对于预防和治疗与PrCP酶活性相关的疾病非常有用，如异常代谢，包括肥胖、糖尿病、代谢综合征、肥胖相关疾病和糖尿病相关疾病。
• Discovery of Potent, Selective, and Brain-Penetrant 1<i>H</i>-Pyrazol-5-yl-1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridines as Anaplastic Lymphoma Kinase (ALK) Inhibitors
  作者：Makoto Fushimi、Ikuo Fujimori、Takeshi Wakabayashi、Tomoaki Hasui、Youichi Kawakita、Keisuke Imamura、Tomoko Kato、Morio Murakami、Tsuyoshi Ishii、Yorifumi Kikko、Maki Kasahara、Atsushi Nakatani、Yuto Hiura、Maki Miyamoto、Kumar Saikatendu、Hua Zou、Scott Weston Lane、J. David Lawson、Hiroshi Imoto

  DOI：10.1021/acs.jmedchem.8b01630

  日期：2019.5.23

  Anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, is predominantly expressed in the brain and implicated in neuronal development and cognition. However, the detailed function of ALK in the central nervous system (CNS) is still unclear. To elucidate the role of ALK in the CNS, it was necessary to discover a potent, selective, and brain-penetrant ALK inhibitor. Scaffold hopping and lead optimization of N-(2,4-difluorobenzyl)-3-(1H-pyrazol-5yl)imidazo[1,2-b]pyridazin-6-amine 1 guided by a cocrystal structure of compound 1 bound to ALK resulted in the identification of (6-(1-(5-fluoropyridin-2-yl)ethoxy)-1-(5-methyl-1H-pyrazol-3-yl)-1H-pyrrolo [2,3-b)]pyridin-3-yl) ( (2S)-2-methylmorpholin-4-yl)methanone 13 as a highly potent, selective, and brain-penetrable compound. Intraperitoneal administration of compound 13 significantly decreased the phosphorylated-ALK (p-ALK) levels in the hippocampus and prefrontal cortex in the mouse brain. These results suggest that compound 13 could serve as a useful chemical probe to elucidate the mechanism of ALK-mediated brain functions and the therapeutic potential of ALK inhibition.