Carbamic acid, N-[3-[6-[[(2-amino-2-oxoethyl)amino]carbonyl]-5-hydroxy-3-pyridinyl]phenyl]-, 1,1-dimethylethyl ester | 1415226-41-3

• 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: Carbamic acid, N-[3-[6-[[(2-amino-2-oxoethyl)amino]carbonyl]-5-hydroxy-3-pyridinyl]phenyl]-, 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[3-[6-[(2-amino-2-oxoethyl)carbamoyl]-5-hydroxypyridin-3-yl]phenyl]carbamate
• CAS: 1415226-41-3
• 化学式: C₁₉H₂₂N₄O₅
• 分子量: 386.4
• InChiKey: GCSJNAUXPIBIOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  6

文献信息

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

  公开号：US20120309977A1

  公开（公告）日：2012-12-06

  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]aminolacetic 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.

  本发明揭示了制备[(3-羟基吡啶-2-羰基)氨基]-烷基酸的方法，其中包括5-芳基取代和5-杂环取代的[(3-羟基吡啶-2-羰基)氨基]乙酸衍生物。此外，还揭示了制备[(3-羟基吡啶-2-羰基)-氨基]乙酸的前药的方法，例如[(3-羟基吡啶-2-羰基)氨基]乙酸酯和[(3-羟基吡啶-2-羰基)氨基]乙酸酰胺。这些揭示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-ARYL OR 5-HETEROARYL SUBSTITUTED 3-HYDROXYPYRIDIN-2-YL-CARBONYLAMINO-ALKANOIC ACID DERIVATIVES AND SALTS THEREOF AS WELL AS THEIR PREPARATION FROM THE RESPECTIVE 3-HYDROXY-PICOLINIC ACID DERIVATIVES
  申请人：Akebia Therapeutics Inc.

  公开号：EP3000808A1

  公开（公告）日：2016-03-30

  The present invention relates to 5-aryl or 5-heteroaryl substituted 3-hydroxypyridin-2-yl-carbonylamino-alkanoic acid derivatives and salts thereof as well as to their preparation from the respective 3-hydroxy-picolinic acid derivatives. The final compounds are prolyl hydroxylase inhibitors.

  本发明涉及 5-芳基或 5-杂芳基取代的 3-羟基吡啶-2-基-羰基氨基-烷酸衍生物及其盐，以及由相应的 3-羟基-匹考林酸衍生物制备它们。最终化合物是脯氨酰羟化酶抑制剂。
• 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。