5-Chloro-thiophene-2-carboxylic acid methyl-{(S)-2-oxo-3-[4-(3-oxo-morpholin-4-yl)-phenyl]-oxazolidin-5-ylmethyl}-amide | 865479-76-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 5-Chloro-thiophene-2-carboxylic acid methyl-{(S)-2-oxo-3-[4-(3-oxo-morpholin-4-yl)-phenyl]-oxazolidin-5-ylmethyl}-amide
• 英文别名: 5-Chloro-N-methyl-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide；5-chloro-N-methyl-N-[[(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide
• CAS: 865479-76-1
• 化学式: C₂₀H₂₀ClN₃O₅S
• 分子量: 449.915
• InChiKey: FAQYFCCIHWKTEZ-HNNXBMFYSA-N

物化性质

• 沸点：
  730.4±60.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-[[(5S)-2-氧代-3-[4-(3-氧代-4-吗啉基)苯基]-5-噁唑烷基]甲基]-1H-异吲哚-1,3(2H)-二酮 在 吡啶 、 sodium hydride 、 甲胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-Chloro-thiophene-2-carboxylic acid methyl-{(S)-2-oxo-3-[4-(3-oxo-morpholin-4-yl)-phenyl]-oxazolidin-5-ylmethyl}-amide
  参考文献：
  名称：

  Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939):  An Oral, Direct Factor Xa Inhibitor

  摘要：

  Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.

  DOI：

  10.1021/jm050101d

文献信息

• [EN] PROCESS FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE RIVAROXABAN ET SES INTERMÉDIAIRES
  申请人：ENANTIA S L

  公开号：WO2011080341A1

  公开（公告）日：2011-07-07

  A process for the preparation of rivaroxaban, or a pharmaceutically acceptable salt thereof, or a solvate thereof, including a hydrate, comprising submitting an amine compound of formula (III) wherein R1 is a (C4-C10)-alkyl radical which is attached to the N atom by a tertiary C atom, first to an acylation reaction and then to a dealkylation reaction.

  一种用于制备利伐沙班、其药用可接受盐或其溶剂化物（包括水合物）的方法，包括将式（III）中R1为通过三级碳原子连接到N原子的（C4-C10）烷基基团的胺化合物首先进行酰化反应，然后进行脱烷基化反应。
• [EN] METHOD FOR PREPARATION OF THIOPHENE-2-CARBONYL CHLORIDES WITH OXALYL CHLORIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CHLORURES DE THIOPHÈNE-2-CARBONYLE AVEC DU CHLORURE D'OXALYLE
  申请人：LONZA AG

  公开号：WO2017076844A1

  公开（公告）日：2017-05-11

  The invention discloses a method for the preparation of thiophene-2-carbonyl chlorides starting from thiophenes with oxalyl chloride at elevated temperature with short reaction time.

  该发明揭示了一种从噻吩出发，利用草酸氯酰氯在高温下短时间反应制备噻吩-2-羰基氯化物的方法。
• PROCESS FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
  申请人：Rafecas Jané Llorenç

  公开号：US20120283434A1

  公开（公告）日：2012-11-08

  A process for the preparation of rivaroxaban, or a pharmaceutically acceptable salt thereof, or a solvate thereof, including a hydrate, comprising submitting an amine compound of formula (III) wherein R 1 is a (C 4 -C 10 )-alkyl radical which is attached to the N atom by a tertiary C atom, first to an acylation reaction and then to a dealkylation reaction.

  一种制备利伐沙班、其药用可接受盐或其溶剂化物，包括水合物的方法，包括将式（III）中R1为（C4-C10）-烷基基团，其通过三级碳原子连接到N原子的胺化合物，首先进行酰化反应，然后进行脱烷基化反应。