N-m-Toluoyl-aziridin | 2453-31-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-m-Toluoyl-aziridin
• 英文别名: 1-(3-methyl-benzoyl)-aziridine；Aziridin-1-yl-(3-methylphenyl)methanone
• CAS: 2453-31-8
• 化学式: C₁₀H₁₁NO
• 分子量: 161.203
• InChiKey: FAKPNCVFPWQGFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 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：
  20.1
• 氢给体数：
  0
• 氢受体数：
  1

文献信息

• PROCESS FOR PREPARING [(3-HYDROXYPYRIDINE-2-CARBONYL)AMINO]ALKANOIC ACIDS, ESTERS AND AMIDES
  申请人：Akebia Therapeutics, Inc.

  公开号：US20150361043A1

  公开（公告）日：2015-12-17

  Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and [3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

  本发明涉及制备[(3-羟基吡啶-2-羧基)氨基]-烷基酸，其衍生物，包括5-芳基取代和5-杂环芳基取代的[(3-羟基吡啶-2-羧基)氨基]乙酸。此外，还公开了制备[(3-羟基吡啶-2-羧基)氨基]乙酸的前药的方法，例如[(3-羟基吡啶-2-羧基)氨基]乙酸酯和[3-羟基吡啶-2-羧基]氨基}乙酸酰胺。所公开的化合物可用作脯氨酸羟化酶抑制剂或用于治疗需要脯氨酸羟化酶抑制的疾病。
• 5-((HALOPHENYL)-3-HALO-PYRIDIN-2-YL)-NITRILE DERIVATIVES AS INTERMEDIATES IN THE PREPARATION OF [(5-(HALOPHENYL)-3-HYDROXYPYRIDINE-2-CARBONYL)-AMINO]ALKANOIC ACID DERIVATIVES
  申请人：Akebia Therapeutics Inc.

  公开号：EP3290404A1

  公开（公告）日：2018-03-07

  The present invention relates to 5-((halophenyl)-3-halo-pyridin-2-yl)-nitril derivatives used as intermediates in the preparation of [(5-(halophenyl)-3-hydroxypyridine-2-carbonyl)-amino]alkanoic acids. The final compounds are prodrugs of prolyl hydroxylase inhibitors.

  本发明涉及用作制备[(5-(卤苯基)-3-羟基吡啶-2-羰基)-氨基]烷酸的中间体的 5-((卤苯基)-3-卤吡啶-2-基)-nitril 衍生物。最终化合物是脯氨酰羟化酶抑制剂的原药。
• PROCESS FOR PREPARING [(5-(3-CHLOROPHENYL)-3-HYDROXYPYRIDINE-2-CARBONYL)-AMINO]ACETIC ACID FROM 5-((3-CHLOROPHENYL)-3-CHLORO-PYRIDIN-2-YL)-NITRILE, AND PROCESS FOR PREPARING 5-((HALOPHENYL)-3-HALO-PYRIDIN-2-YL)-NITRILE DERIVATIVES
  申请人：Akebia Therapeutics Inc.

  公开号：EP3683209A1

  公开（公告）日：2020-07-22

  A process for preparing compound (5): comprising: A. reacting (3-chlorophenyl)boronic acid: with 3,5-dichloro-2-cyanopyridine: in the presence of [1,1'-bis (diphenylphosphino)ferrocene]dichloro palladium(II) and K2 CO3 in DMF at 45C° to form 5-(3-chlorophenyl)-3 -chloro-2-cyanopyridine: B. reacting 5-(3-chlorophenyl)-3-chloro-2-cyanopyridine with sodium methoxide in methanol at reflux to form 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine: C. reacting 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine with 48% hydrobromic acid at reflux to form 5-(3-chlorophenyl)-3-hydroxypyridine-2-carboxylic acid: D. reacting 5-(3-chlorophenyl)-3-hydroxypyridine-2-carboxylic acid with glycine methyl ester: in the presence of CDI and DIPEA in DMSO at room temperature to form methyl [5-(3-chlorophenyl)-3-hydroxypyridin-2-yl]amino}acetate: E. reacting methyl [5-(3-chlorophenyl)-3-hydroxypyridin-2-yl]amino}acetate with sodium hydroxide in THF to form compound (5):

  一种制备化合物(5)的工艺： 包括： A. (3-氯苯基)硼酸与 3,5-二氯-2-氰基吡啶反应： 与 3,5-二氯-2-氰基吡啶反应： 在[1,1'-双(二苯基膦)二茂铁]二氯钯(II)和 K2 CO3 的存在下，于 45C° 在 DMF 中反应生成 5-(3-氯苯基)-3-氯-2-氰基吡啶： B. 将 5-(3-氯苯基)-3-氯-2-氰基吡啶与甲醇中的甲醇钠在回流条件下反应，生成 5-(3-氯苯基)-3-甲氧基-2-氰基吡啶： C. 将 5-(3-氯苯基)-3-甲氧基-2-氰基吡啶与 48%的氢溴酸在回流条件下反应，生成 5-(3-氯苯基)-3-羟基吡啶-2-羧酸： D. 5-(3-氯苯基)-3-羟基吡啶-2-羧酸与甘氨酸甲酯反应： 在 CDI 和 DIPEA 的存在下，于室温在二甲基亚砜中反应生成[5-(3-氯苯基)-3-羟基吡啶-2-基]氨基}乙酸甲酯： E. 将[5-(3-氯苯基)-3-羟基吡啶-2-基]氨基}乙酸甲酯与氢氧化钠在 THF 中反应生成化合物 (5)：
• PROCESS FOR PREPARING N-[[5-(3-CHLOROPHENYL)-3-HYDROXY-2-PYRIDINYL]CARBONYL]-GLYCINE FROM 5-(3-CHLOROPHENYL)-3-HYDROXY-2-PYRIDINE CARBOXYLIC ACID
  申请人：Akebia Therapeutics Inc.

  公开号：EP4026829A1

  公开（公告）日：2022-07-13

  The present invention relates to a process for preparing N-[[5-(3- chlorophenyl)-3-hydroxy-2-pyridinyl]carbonyl]-glycine (compound (5)), from the intermediates 5-(3-chlorophenyl)-3-chloro-2- pyridinecarbonitrile (compound (1)), 5-(3-chlorophenyl)-3-methoxy-2- pyridinecarbonitrile (compound (2)), 5-(3-chlorophenyl)-3-hydroxy-2- pyridinecarboxylic acid (compound (3)). Compound (5) is an intermediate in the preparation of prolyl hydroxylase inhibitors.

  本发明涉及一种由中间体 5-(3-氯苯基)-3-氯-2-吡啶甲腈(化合物(1))制备 N-[[5-(3-氯苯基)-3-羟基-2-吡啶基]羰基]-甘氨酸(化合物(5))的工艺、5-(3-氯苯基)-3-甲氧基-2-吡啶甲腈（化合物（2））、5-(3-氯苯基)-3-羟基-2-吡啶甲酸（化合物（3））。化合物 (5) 是制备脯氨酰羟化酶抑制剂的中间体。
• 5-((HALOPHENYL)-3-HYDROXY-PYRIDIN-2-YL)-CARBOXYLIC ACID DERIVATIVES AS INTERMEDIATES FOR THE PREPARATION OF CARBONYLAMINO ALKANOIC ACIDS, ESTERS AND AMIDES THEREOF
  申请人：Akebia Therapeutics Inc.

  公开号：EP3000808B1

  公开（公告）日：2017-09-27