N-ethyl-3-fluoro-3-[3-fluoro-(4-pyrrolidin-1-ylmethyl)phenyl]cyclobutanecarboxamide | 935840-31-6

• 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: N-ethyl-3-fluoro-3-[3-fluoro-(4-pyrrolidin-1-ylmethyl)phenyl]cyclobutanecarboxamide
• 英文别名: 3-fluoro-3-(3-fluoro-4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanecarboxylic acid ethylamide；trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutanecarboxamide；N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide
• CAS: 935840-31-6
• 化学式: C₁₈H₂₄F₂N₂O
• 分子量: 322.398
• InChiKey: SXMBKHYDZOCBMT-UHFFFAOYSA-N

物化性质

• 沸点：
  460.5±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-ethyl-3-fluoro-3-[3-fluoro-(4-pyrrolidin-1-ylmethyl)phenyl]cyclobutanecarboxamide 在 盐酸 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 3-fluoro-3-(3-fluoro-4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanecarboxylic acid ethylamide hydrochloride
  参考文献：
  名称：

  WO2007/49123

  摘要：

  公开号：
• 作为产物：
  描述：

  N-ethyl-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-3-hydroxycyclobutanecarboxamide 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 生成 N-ethyl-3-fluoro-3-[3-fluoro-(4-pyrrolidin-1-ylmethyl)phenyl]cyclobutanecarboxamide
  参考文献：
  名称：

  Synthesis of an H₃ Antagonist via Sequential One-Pot Additions of a Magnesium Ate Complex and an Amine to a 1,4-Ketoester followed by Carbonyl-Directed Fluoride Addition

  摘要：

  We describe the development of an efficient and scalable process for the preparation of fluorocyclobutane-containing H-3 antagonist, 1. The synthesis was accomplished by the chemoselective addition of a magnesium ate complex and an amine to a 1,4-ketoester in a one-pot sequence, followed by a diastereoselective carbonyl-directed fluorination. The chemoselective addition of the magnesium ate complex to the ketoester benefited from tight stoichiometric control, short addition times, and lower reaction temperatures, and thus was amenable to rapid mixing and excellent heat transfer in a flow reactor.

  DOI：

  10.1021/op300093j

文献信息

• Novel Cyclopropabenzofuranyl Pyridopyrazinediones
  申请人：Pfizer Inc.

  公开号：US20160222007A1

  公开（公告）日：2016-08-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I wherein X, R 1 , R 2a , R 2b , R 4a , R 4b , R 5a , R 5b , R 6 , R 7 , R 10 , R 11 , and y are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  揭示了化合物及其在药学上可接受的盐，其中该化合物具有Formula I的结构 其中X，R 1 ，R 2a ，R 2b ，R 4a ，R 4b ，R 5a ，R 5b ，R 6 ，R 7 ，R 10 ，R 11 和y如规范中所定义。还公开了相应的药物组合物、治疗方法、合成方法和中间体。
• Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
  申请人：BRODNEY Michael Aaron

  公开号：US20130053373A1

  公开（公告）日：2013-02-28

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被揭示，其中所述化合物具有规范中定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被揭示。
• TOLUENE SULFONIC ACID SALT OF A THERAPEUTIC COMPOUND AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Butler Todd W.

  公开号：US20080176925A1

  公开（公告）日：2008-07-24

  The present invention is directed to the tosylate salt of trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)-phenyl]-cyclobutanecarboxamide (1): to solvates (e.g., hydrates) thereof, to polymorphs thereof, to pharmaceutical compositions thereof and to a method of treating depression, mood disorders, schizophrenia, anxiety disorders, cognitive disorders, Alzheimer's disease, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), psychotic disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper- and hypo-motility and acidic secretion of the gastro-intestinal tract comprising administering a therapeutically effective amount thereof.

  本发明涉及对氟醚脲基环丁烷羧酰胺的对甲苯磺酸盐（1）：其溶剂化合物（例如水合物）、其多型体、其药物组合物以及治疗抑郁症、情绪障碍、精神分裂症、焦虑症、认知障碍、阿尔茨海默病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、精神障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸道疾病、过敏、过敏引起的气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低蠕动和酸性分泌包括给予其治疗有效量的方法。
• TREATMENT OF OSTEOARTHRITIS PAIN
  申请人：AbbVie Inc.

  公开号：US20160089378A1

  公开（公告）日：2016-03-31

  This invention discloses a method of treatment of osteoarthritis pain by administration of a histamine H 3 receptor antagonist, described herein, a salt thereof, or a composition comprising such compound or salt.

  本发明公开了一种治疗骨关节炎疼痛的方法，通过给予本文描述的组织胺H3受体拮抗剂，其盐，或包含该化合物或盐的组合物。
• HISTAMINE-3 RECEPTOR ANTAGONISTS
  申请人：Wager T. Travis

  公开号：US20080096955A1

  公开（公告）日：2008-04-24

  This invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a process of preparation of a compound of formula I, a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), psychotic disorders, cognitive disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.

  本发明涉及一种式I的化合物，如本文所定义，或其药学上可接受的盐；包含式I化合物的制药组合物；制备式I化合物的方法；一种治疗通过拮抗组胺H3受体可治疗的紊乱或病症的方法，该方法包括向需要此类治疗的哺乳动物投与上述式I化合物；以及治疗所选组中的紊乱或病症的方法，所选组包括抑郁症、情绪障碍、精神分裂症、焦虑症、阿尔茨海默病、注意力缺陷多动障碍（ADHD）、精神病性疾病、认知障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸系统疾病、过敏、过敏性气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低运动和酸性分泌，该方法包括向需要此类治疗的哺乳动物投与上述式I化合物。