(2R,4R)-2-[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester | 910823-59-5

• 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: (2R,4R)-2-[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: (2r,4r)-2-[2-Fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2R,4R)-2-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]-4-methoxypyrrolidine-1-carboxylate
• CAS: 910823-59-5
• 化学式: C₂₂H₂₆FN₃O₅
• 分子量: 431.464
• InChiKey: TWZUAEAZXKKKJV-CRAIPNDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4R)-2-[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester 以100的产率得到(2R,4R)-4-methoxy-pyrrolidine-2-carboxylic acid [2-fluoro-4-(2-oxo-pyridin-1-yl)-phenyl]-amide hydrochloride
  参考文献：
  名称：

  WO2006100565A1

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氟-4-碘苯胺 在 copper(l) iodide 、 trans-1,2-cyclohexanediamine potassium phosphate 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三乙胺 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 41.0h， 生成 (2R,4R)-2-[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2006/100565

  摘要：

  公开号：

文献信息

• Factor Xa Inhibitor Crystalline Forms
  申请人：Samas Brian

  公开号：US20080194643A1

  公开（公告）日：2008-08-14

  Disclosed are crystalline forms A, B and C of 1,2-Pyrrolidinedicarboxamide, N1-(4-chlorophenyl)-N2-[2-fluoro-4-(2-oxo-1(2H)-pyridinyl)phenyl]-4-methoxy-, (2R,4R)-(9Cl). These crystalline forms are characterized by their powder X-ray diffraction, solid-state NMR, as well as methods for the preparation and pharmaceutical compositions of the same which are useful for the treatment of acute, subacute, or chronic thrombotic disorders including treatment of venous thrombosis, arterial thrombosis, pulmonary embolism, myocardial infarction, cerebral infarction, restenosis, atherosclerosis, angina, primary and secondary deep vein thrombosis, thromboembolism associated with cardiovascular disease, including, but not limited to, acute coronary syndrome, atrial fibrillation, cardiac valve replacement and deep vein thrombosis. The crystalline forms of the present invention are also useful for the treatment of cancer, sepsis and diabetes.

  本发明涉及1,2-吡咯烷二甲酰胺，N1-(4-氯苯基)-N2-[2-氟-4-(2-氧代-1(2H)-吡啶基)苯基]-4-甲氧基，(2R,4R)-(9Cl)的晶体形式A、B和C。这些晶体形式的特征是它们的粉末X射线衍射，固态核磁共振，以及制备方法和制备的药物组合物，可用于治疗急性、亚急性或慢性血栓性疾病，包括静脉血栓形成、动脉血栓形成、肺栓塞、心肌梗死、脑梗死、再狭窄、动脉粥样硬化、心绞痛、原发性和继发性深静脉血栓形成、与心血管疾病相关的血栓栓塞，包括但不限于急性冠状动脉综合征、心房颤动、心脏瓣膜置换和深静脉血栓形成。本发明的晶体形式还可用于治疗癌症、败血症和糖尿病。
• CRYSTALLINE FORMS OF A KNOWN PYRROLIDINE FACTOR XA INHIBITOR
  申请人：Warner-Lambert Company LLC

  公开号：EP1891044A1

  公开（公告）日：2008-02-27
• [EN] CRYSTALLINE FORMS OF A KNOWN PYRROLIDINE FACTOR XA INHIBITOR<br/>[FR] FORMES CRISTALLINES D'UN INHIBITEUR PYRROLIDINE CONNU DU FACTEUR XA
  申请人：WARNER LAMBERT CO

  公开号：WO2006100565A1

  公开（公告）日：2006-09-28

  [EN] Disclosed are crystalline forms A, B and C of 1 ,2-Pyrrolidinedicarboxamide, N1 -(4- chlorophenyl)-N2-[2-fluoro-4-(2-oxo-1 (2H)-pyridinyl)phenyÊ]-4-methoxy-, (2R,4R)- (9Cl). These crystalline forms are characterized by their powder X-ray diffraction, solid-state NMR, as well as methods for the preparation and pharmaceutical compositions of the same which are useful for the treatment of acute, subacute, or chronic thrombotic disorders including treatment of venous thrombosis, arterial thrombosis, pulmonary embolism, myocardial infarction, cerebral infarction, restenosis, atherosclerosis, angina, primary and secondary deep vein thrombosis, thromboembolism associated with cardiovascular disease, including, but not limited to, acute coronary syndrome, atrial fibrillation, cardiac valve replacement and deep vein thrombosis. The crystalline forms of the present invention are also useful for the treatment of cancer, sepsis and diabetes.
  [FR] L'invention concerne les formes cristallines A, B et C de 1,2-Pyrrolidinedicarboxamide, N1 -(4- chlorophényl)-N2-[2-fluoro-4-(2-oxo-1 (2H)-pyridinyl)phényl]-4-méthoxy-, (2R,4R)- (9Cl). Ces formes cristallines sont caractérisées par leur diffraction des rayons X sur poudre et par leur RMN en phase solide. L'invention concerne également des procédés de préparation de ces formes cristallines, et des compositions pharmaceutiques de ces formes cristallines, qui peuvent servir au traitement des troubles thrombotiques aigus, subaigus ou chroniques, notamment au traitement des thromboses veineuses, des thromboses artérielles, des embolies pulmonaires, des infarctus du myocarde, des infarctus cérébraux, des resténoses, de l'athérosclérose, de l'angine de poitrine, des thromboses veineuses profondes primaires et secondaires, des thromboembolies associées à des maladies cardiovasculaires, notamment mais non exclusivement au syndrome coronarien aigu, à la fibrillation auriculaire, au remplacement des valvules cardiaques, et aux thromboses veineuses profondes. Les formes cristallines décrites conviennent également pour le traitement du cancer, des sepsies et du diabète.