methyl 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylate | 928134-37-6

• 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: methyl 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylate
• 英文别名: methyl 5-(4-cyano-2-fluorophenyl)-5H,6H,7H-pyrrolo[1,2-c]imidazole-5-carboxylate；5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester；Methyl 5-(4-cyano-2-fluorophenyl)-6,7-dihydropyrrolo[1,2-c]imidazole-5-carboxylate
• CAS: 928134-37-6
• 化学式: C₁₅H₁₂FN₃O₂
• 分子量: 285.278
• InChiKey: CRLPEWCHUMEPPN-UHFFFAOYSA-N

物化性质

• 沸点：
  490.2±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylate 生成 osilodrostat
  参考文献：
  名称：

  ACS Med. Chem. Lett. 2013, 4, 1203-1207

  摘要：

  DOI：
• 作为产物：
  描述：

  methyl 2-(4-cyano-2-fluorophenyl)-2-(5-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-1-yl)acetate 在 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 42.0h， 以4.2 g的产率得到methyl 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylate
  参考文献：
  名称：

  [EN] 3-FLUORO-BENZONITRILE INHIBITORS OF 11-BETA-HYDROXYLASE
  [FR] INHIBITEURS 3-FLUORO-BENZONITRILES DE LA 11-BÊTA-HYDROXYLASE

  摘要：

  公开号：

  WO2016109361A3

文献信息

• Organic compounds
  申请人：Ksander Michael Gary

  公开号：US20070049616A1

  公开（公告）日：2007-03-01

  The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种I式化合物：所述化合物是醛固酮合成酶和芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香化酶介导的疾病或疾病。因此，I式化合物可用于治疗低钾血症、高血压、充血性心力衰竭、心房颤动、肾功能衰竭，特别是慢性肾功能衰竭、再狭窄、动脉粥样硬化、X综合征、肥胖、肾病、心肌梗死后、冠心病、炎症、胶原蛋白增生、纤维化如心脏或心肌纤维化以及高血压和内皮功能障碍后的重塑，男性乳房发育过大、骨质疏松症、前列腺癌、子宫内膜异位症、子宫肌瘤、功能性子宫出血、子宫内膜增生、多囊卵巢综合征、不孕症、纤维囊性乳腺疾病、乳腺癌和纤维囊性乳房病。最后，本发明还提供了一种药物组合物。
• [EN] PROCESS FOR THE PRODUCTION OF CONDENSED IMIDAZOLO DERIVATIVES<br/>[FR] PROCÉDÉ DE PRODUCTION DE DÉRIVÉS D'IMIDAZOLES CONDENSÉS
  申请人：NOVARTIS AG

  公开号：WO2016120821A1

  公开（公告）日：2016-08-04

  The present invention relates to a process for providing the compound of formula I, comprising the step of reacting a compound of formula VII with a base in the presence of an alkaline- or alkaline earth metal salt (MX), wherein LG is a leaving group. The presence of an alkaline- or alkaline earth metal salt was surprisingly found to render said reaction highly reliable in terms of the yield and purity of the compound of formula I obtained. In a further aspect, the present invention relates to the compound of formula I, having less than an amount of 1.50% or less than an amount of 1.25% or less than an amount of 1.00% or less than an amount of 0.75% or less than an amount of 0.50% or less than an amount of 0.25% or less than an amount of 0.10% of the compound of formula VIII.

  本发明涉及一种提供式I化合物的方法，包括在碱性或碱土金属盐（MX）存在下，将式VII化合物与碱反应，其中LG是离去基团。惊人地发现，碱性或碱土金属盐的存在可以使得所得到的式I化合物的产率和纯度高度可靠。在另一个方面，本发明涉及式I化合物，其含有少于1.50％或少于1.25％或少于1.00％或少于0.75％或少于0.50％或少于0.25％或少于0.10％的式VIII化合物。
• Organic Compounds
  申请人：Ksander Gary Michael

  公开号：US20130287789A1

  公开（公告）日：2013-10-31

  The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种化合物I，其为醛固酮合成酶和芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香化酶介导的疾病或疾病。因此，化合物I可用于治疗低钾血症、高血压、充血性心力衰竭、心房颤动、肾衰竭，特别是慢性肾衰竭、再狭窄、动脉粥样硬化、X综合症、肥胖症、肾病、心肌梗死后、冠心病、炎症、胶原形成增加、纤维化如心脏或心肌纤维化以及高血压和内皮功能障碍后的重塑、男性乳腺增生、骨质疏松症、前列腺癌、子宫内膜异位症、子宫肌瘤、功能性子宫出血、子宫内膜增生、多囊卵巢综合症、不孕症、纤维囊性乳房病、乳腺癌和纤维囊性乳房病。最后，本发明还提供了一种制药组合物。
• Condensed imidazolo derivatives for the inhibition of aromatase
  申请人：Novartis AG

  公开号：EP2256118A1

  公开（公告）日：2010-12-01

  The present invention relates to novel imidazole derivatives that are used as aromatase inhibitors, as well as for treatment of a disorder or disease mediated by aromatase.

  本发明涉及可用作芳香化酶抑制剂以及用于治疗由芳香化酶介导的紊乱或疾病的新型咪唑衍生物。
• Process for the production of condensed imidazolo derivatives
  申请人：Novartis AG

  公开号：US10556869B2

  公开（公告）日：2020-02-11

  The present invention relates to a process for providing the compound of formula I, comprising the step of reacting a compound of formula VII with a base in the presence of an alkaline- or alkaline earth metal salt (MX), wherein LG is a leaving group. The presence of an alkaline- or alkaline earth metal salt was surprisingly found to render said reaction highly reliable in terms of the yield and purity of the compound of formula I obtained. In a further aspect, the present invention relates to the compound of formula I, having less than an amount of 1.50% or less than an amount of 1.25% or less than an amount of 1.00% or less than an amount of 0.75% or less than an amount of 0.50% or less than an amount of 0.25% or less than an amount of 0.10% of the compound of formula VIII.

  本发明涉及一种提供式 I 化合物的工艺，包括在碱或碱土金属盐 (MX) 存在下使式 VII 化合物与碱反应的步骤，其中 LG 为离去基团。令人惊讶的是，碱金属或碱土金属盐的存在使所述反应在所获得的式 I 化合物的产率和纯度方面具有高度可靠性。在另一个方面，本发明涉及式 I 化合物，其式 VIII 化合物的含量小于 1.50%或小于 1.25%或小于 1.00%或小于 0.75%或小于 0.50%或小于 0.25%或小于 0.10%。