4-(4-(methylamino)phenyl)morpholin-3-one | 1224684-98-3

• 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: 4-(4-(methylamino)phenyl)morpholin-3-one
• 英文别名: 4-[4-(Methylamino)phenyl]morpholin-3-one；4-[4-(methylamino)phenyl]morpholin-3-one
• CAS: 1224684-98-3
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: JAHXVKJQRGGXCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-(methylamino)phenyl)morpholin-3-one 在 4-二甲氨基吡啶 、 10% Pd(OH)₂ on C 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， 生成 (S)-2-(2-(4-chlorophenyl)acetyl)-N-methyl-N-(4-(3-oxomorpholino)phenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032
• 作为产物：
  描述：

  3-吗啉酮 、 4-溴-N-甲基苯胺 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 生成 4-(4-(methylamino)phenyl)morpholin-3-one
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032

文献信息

• [EN] PROCESSES FOR THE PREPARATION OF 5-CHLORO-N-({(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL) PHENYL]-1,3-OXAZOLIDIN-5-YL}METHYL)-2-THIOPHENE-CARBOXAMIDE AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION DU 5-CHLORO-N-({(5S)-2-OXO-3-[4-(3-OXO-4- MORPHOLINYL) PHÉNYL]-1,3-OXAZOLIDIN-5-YL}MÉTHYL)-2-THIOPHÈNE-CARBOMAXIDE ET DE SES INTERMÉDIAIRES
  申请人：SYMED LABS LTD

  公开号：WO2013046211A1

  公开（公告）日：2013-04-04

  TThe present invention provides processes for the preparation of 5-chloro-N-((5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophene-carboxamide (I) and intermediates thereof. Also provides novel intermediates and their use in the synthesis of oxazolidine derivatives.

  本发明提供了用于制备5-氯-N-((5S)-2-氧代-3-[4-(3-氧代-4-吗啉基)苯基]-1,3-噁唑烷-5-基}甲基)-2-噻吩甲酰胺(I)及其中间体的方法。还提供了新型中间体及其在噁唑烷衍生物合成中的应用。
• [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。
• METHOD FOR THE PREPARATION OF RIVORAXABAN
  申请人：Sturm Hubert

  公开号：US20130184457A1

  公开（公告）日：2013-07-18

  The present invention relates to the use of a compound having the formula (II) for the preparation of a compound having the formula (V). Methods of preparing the compound having the formula (V) using the compound having the formula (II) are also described. Individual reaction steps as well as intermediates are additionally claimed.

  本发明涉及使用具有式（II）的化合物制备具有式（V）的化合物。还描述了使用具有式（II）的化合物制备具有式（V）的方法。此外，还宣称了各个反应步骤以及中间体。
• METHOD FOR PREPARING RIVAROXABAN INTERMEDIATE
  申请人：China National Medicines Guorui Pharmaceutical Co., Ltd.

  公开号：EP2837628B1

  公开（公告）日：2016-11-30
• PYRROLIDIN-1,2-DICARBONSÄURE-1-(PHENYLAMID)-2-(4-(3-OXO-MORPHOLIN-4-YL)-PHENYLAMID) DERIVATE UND VERWANDTE VERBINDUNGEN ALS INHIBITOREN DES KOAGULATIONSFAKTORS XA ZUR BEHANDLUNG VON THROMBOEMBOLISCHEN ERKRANKUNGEN
  申请人：Merck Patent GmbH

  公开号：EP1720844B1

  公开（公告）日：2009-04-29