4-(2-oxomorpholino)aniline

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-(2-oxomorpholino)aniline
• 英文别名: 4-(4-aminophenyl)morpholin-2-one；N-(4-aminophenyl)morpholin-3-one
• 化学式: C₁₀H₁₂N₂O₂
• 分子量: 192.217
• InChiKey: MUPPVCHMRQPGFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-oxomorpholino)aniline 、 (S)-N-缩水甘油邻苯二甲酰亚胺 以 甲醇 、 水 为溶剂， 反应 20.0h， 以75%的产率得到2-[(2R)-2-羟基-3-[[4-(3-氧代-4-吗啉)苯基]氨基]丙基]-1H-异吲哚-1,3(2H)-二酮
  参考文献：
  名称：

  [EN] A METHOD OF MANUFACTURING 2-({(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]- L,3-OXAZOLIDIN-5-YL}METHYL)-LH-ISOINDOL-L,3(2H)-DIONE WITH A HIGH OPTICAL PURITY
  [FR] PROCÉDÉ DE FABRICATION D'UNE 2-({(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHÉNYL]- L,3-OXAZOLIDIN-5-YL}MÉTHYL)-LH-ISOINDOL-L,3(2H)-DIONE À LA PURETÉ OPTIQUE ÉLEVÉE

  摘要：

  公开号：

  WO2012041263A3

文献信息

• Synthesis and Thrombin, Factor Xa and U46619 Inhibitory Effects of Non-Amidino and Amidino N2-Thiophenecarbonyl- and N2-Tosylanthranilamides
  作者：Soo Lee、Wonhwa Lee、ThiHa Nguyen、Il Um、Jong-Sup Bae、Eunsook Ma

  DOI：10.3390/ijms18061144

  日期：——

  Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N2-thiophencarbonyl- and N2-tosyl anthranilamides 1–20 and six amidino N2-thiophencarbonyl- and N2-tosylanthranilamides 21–26 were synthesized to evaluate their activated partial thromboplastin time (aPTT) and prothrombin time (PT) using human plasma at a concentration of 30 µg/mL in vitro. As a result, compounds 5, 9, and 21–23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21–23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21–23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced by U46619 in vitro and ex vivo. Among the derivatives evaluated, N-(3′-amidinophenyl)-2-((thiophen-2′′-yl)carbonylamino)benzamide (21) was the most active compound.

  凝血酶（因子IIa）和因子Xa（FXa）是内在和外在凝血途径交汇处的关键酶，也是开发新型抗凝药物中最具吸引力的药理学靶点。合成20种非脒基N2-噻酚羰基-和N2-对甲苯磺酰基邻氨基苯甲酰胺1-20以及6种脒基N2-噻酚羰基-和N2-对甲苯磺酰基邻氨基苯甲酰胺21-26，以评估它们在体外以30µg/mL浓度下对人血浆的活化部分凝血活酶时间（aPTT）和凝血酶原时间（PT）。结果，选择了化合物5、9和21-23进一步研究其抗血栓活性。5、9和21-23的抗凝特性显著表现为体外PT和aPTT的浓度依赖性延长、体内出血时间延长以及体外凝血时间延长。这些化合物浓度依赖性地抑制了凝血酶和FXa的活性，并抑制了人内皮细胞中凝血酶和FXa的生成。此外，数据显示5、9和21-23显著抑制了凝血酶催化的纤维蛋白聚合和鼠标血小板聚集，以及体外和离体由U46619诱导的血小板聚集。在评估的衍生物中，N-(3'-脒基苯基)-2-((2''-噻吩基)羰基氨基)苯甲酰胺（21）是最活跃的化合物。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF RIVAROXABAN INVOLVING NOVEL INTERMEDIATE<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE RIVAROXABAN IMPLIQUANT UN NOUVEL INTERMÉDIAIRE
  申请人：UNICHEM LAB LTD

  公开号：WO2018127762A1

  公开（公告）日：2018-07-12

  The present invention relates to the novel key intermediate, 4-4-[(5S)-(Aminomethyl)-2- oxo-l,3-oxazolidin-3-yl]-phenyl}-morpholin-3-one perchlorate, in the synthesis of rivaroxaban. The invention further relates to the crystalline form of novel intermediate, the process to prepare the novel intermediate and method of preparing rivaroxaban using this novel intermediate. The invention provides an improved and efficient process for preparation of Rivaroxaban.

  本发明涉及一种新型关键中间体，即4-4-[(5S)-(氨甲基)-2-氧代-1,3-噁唑烷-3-基]-苯基}-吗啉-3-酮高氯酸盐，在利伐罗班合成中的应用。该发明还涉及该新型中间体的晶体形式，制备该新型中间体的方法以及利用该新型中间体制备利伐罗班的方法。该发明提供了一种改进和高效的利伐罗班制备方法。
• [EN] PROCESSES FOR PREPARING RIVAROXABAN<br/>[FR] PROCÉDÉS DE PRÉPARATION DU RIVAROXABAN
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2013152168A1

  公开（公告）日：2013-10-10

  Processes and intermediates for preparing rivaroxaban, and analogs and derivatives thereof, and pharmaceutically acceptable salts of each of the foregoing, are described herein.

  本文描述了制备利伐罗班以及其类似物和衍生物的过程和中间体，以及上述每种物质的药用可接受盐。
• Process for the preparation of rivaroxaban involving novel intermediate
  申请人：Unichem Laboratories Ltd

  公开号：US11034683B2

  公开（公告）日：2021-06-15

  The present invention relates to the novel key intermediate, 4-4-[(5S)-(Aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-phenyl}-morpholin-3-one perchlorate, in the synthesis of rivaroxaban. The invention further relates to the crystalline form of novel intermediate, the process to prepare the novel intermediate and method of preparing rivaroxaban using this novel intermediate. The invention provides an improved and efficient process for preparation of Rivaroxaban.

  本发明涉及用于合成利伐沙班的新型关键中间体 4-4-[(5S)-(氨甲基)-2-氧代-1,3-恶唑啉-3-基]-苯基}-吗啉-3-酮高氯酸盐。本发明进一步涉及新型中间体的结晶形式、制备该新型中间体的工艺以及使用该新型中间体制备利伐沙班的方法。本发明提供了一种改进的、高效的利伐沙班制备工艺。
• PROCESSES FOR PREPARING RIVAROXABAN
  申请人：Indiana University Research and Technology Corporation

  公开号：EP2834235A1

  公开（公告）日：2015-02-11