反式-N-乙基-3-氟-3-[3-氟-4-(1-吡咯烷基甲基)苯基]-环丁烷甲酰胺 4-甲基苯磺酸盐 | 1039399-17-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 反式-N-乙基-3-氟-3-[3-氟-4-(1-吡咯烷基甲基)苯基]-环丁烷甲酰胺 4-甲基苯磺酸盐
• 中文别名: 反式-N-乙基-3-氟-3-[3-氟-4-(1-吡咯烷基甲基)苯基]-环丁烷甲酰胺4-甲基苯磺酸盐
• 英文名称: PF-03654746 tosylate
• 英文别名: N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide;4-methylbenzenesulfonic acid
• CAS: 1039399-17-1
• 化学式: C₇H₈O₃S*C₁₈H₂₄F₂N₂O
• 分子量: 494.603
• InChiKey: IKAYTZLLIWAEDV-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 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 、 2-甲基四氢呋喃 为溶剂， 反应 4.75h， 生成 反式-N-乙基-3-氟-3-[3-氟-4-(1-吡咯烷基甲基)苯基]-环丁烷甲酰胺 4-甲基苯磺酸盐
  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

• 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。
• TOSYLATE SALT OF A THERAPEUTIC COMPOUND AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Pfizer Products Inc.

  公开号：EP2124933B1

  公开（公告）日：2012-10-17
• US8314139B2
  申请人：——

  公开号：US8314139B2

  公开（公告）日：2012-11-20
• [EN] TOSYLATE SALT OF A THERAPEUTIC COMPOUND AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] SEL TOSYLATE D'UN COMPOSÉ THÉRAPEUTIQUE ET COMPOSITIONS THÉRAPEUTIQUES LE CONTENANT
  申请人：PFIZER PROD INC

  公开号：WO2008090429A1

  公开（公告）日：2008-07-31

  [EN] The present invention is directed to the tosylate salt of trans-N-ethyl-3- fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)-phenyl]-cyclobutanecarboxamide Formula (I):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 Gl tract, hyper- and hypo-motility and acidic secretion of the gastro-intestinal tract comprising administering a therapeutically effective amount thereof.
  [FR] La présente invention porte sur le sel tosylate de trans-N-éthyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylméthyl)-phényl]-cyclobutanecarboxamide représenté par la formule (I) : sur des solvates (par exemple, des hydrates) de celui-ci, sur des polymorphes de celui-ci, sur des compositions pharmaceutiques le contenant et sur un procédé de traitement de la dépression, des troubles de l'humeur, de la schizophrénie, des troubles de l'anxiété, des troubles cognitifs, de la maladie d'Alzheimer, du trouble du déficit de l'attention (ADD), de l'hyperactivité avec déficit de l'attention (ADHD), des troubles psychotiques, des troubles du sommeil, de l'obésité, des étourdissements, de l'épilepsie, du mal des transports, des troubles respiratoires, de l'allergie, des réponses des voies respiratoires induites par une allergie, de la rhinite allergique, de la congestion nasale, de la congestion allergique, de la congestion, de l'hypotension, d'une maladie cardiovasculaire, des maladies du tractus gastro-intestinal, d'une hypermotilité et d'une hypomotilité et d'une sécrétion acide du tractus gastro-intestinal, ce procédé de traitement comprenant l'administration d'une quantité efficace du point de vue thérapeutique d'une telle composition pharmaceutique.