methyl (2S,5R)-5-(3-pyridyl)tetrahydro-2H-2-pyrrolecarboxylate | 229958-56-9

• 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 (2S,5R)-5-(3-pyridyl)tetrahydro-2H-2-pyrrolecarboxylate
• 英文别名: (2S)-cis-5-(3-pyridinyl)proline methyl ester；(2S,5R)-methyl 5-(pyridin-3-yl)pyrrolidine-2-carboxylate；rac-methyl (2R,5S)-5-(pyridin-3-yl)pyrrolidine-2-carboxylate；methyl (2S,5R)-5-pyridin-3-ylpyrrolidine-2-carboxylate
• CAS: 229958-56-9
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: CIOTZMIEMVQPBC-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2S,5R)-5-(3-pyridyl)tetrahydro-2H-2-pyrrolecarboxylate 在 palladium on activated charcoal N-甲基咪唑 、 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 氢气 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 三氟甲烷磺酸甲酯 、 calcium chloride 、 lithium bromide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 8.5h， 生成 1-(3-pyridinyl)-8-azabicyclo<3.2.1>octane
  参考文献：
  名称：

  Conformationally Constrained Nicotines. 1-Pyridinyl-7-azabicyclo[2.2.1]heptane and 1-Pyridinyl-8-azabicyclo[3.2.1]octane Analogues

  摘要：

  Conformationally constrained bicycle analogues of natural (-)-nicotine and unnatural (+)-nicotine have been synthesized from D- and L-glutamic acid, respectively. Regioselective addition of 3-lithiopyridine to the gamma-carbonyl of a protected glutamate was followed by intramolecular imine formation and stereospecific catalytic hydrogenation of the resultant pyrroline to give cis-5-pyridinylproline. A sequence of transformations to convert the ester to bromide was followed by the key intramolecular anionic cyclization at the benzylic position to form the 1-pyridinyl-7-azabicyclo[2.2.1]heptane analogue. Alternatively, homologation of the ester of cis-5-pyridinylproline and conversion to bromide allowed cyclization to the 1-pyridinyl-7-azabicyclo[3.2.1]octane analogues.

  DOI：

  10.1021/jo990130u
• 作为产物：
  描述：

  3-碘吡啶 在 盐酸 、 acetate buffer 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 methyl (2S,5R)-5-(3-pyridyl)tetrahydro-2H-2-pyrrolecarboxylate
  参考文献：
  名称：

  Conformationally Constrained Nicotines. 1-Pyridinyl-7-azabicyclo[2.2.1]heptane and 1-Pyridinyl-8-azabicyclo[3.2.1]octane Analogues

  摘要：

  Conformationally constrained bicycle analogues of natural (-)-nicotine and unnatural (+)-nicotine have been synthesized from D- and L-glutamic acid, respectively. Regioselective addition of 3-lithiopyridine to the gamma-carbonyl of a protected glutamate was followed by intramolecular imine formation and stereospecific catalytic hydrogenation of the resultant pyrroline to give cis-5-pyridinylproline. A sequence of transformations to convert the ester to bromide was followed by the key intramolecular anionic cyclization at the benzylic position to form the 1-pyridinyl-7-azabicyclo[2.2.1]heptane analogue. Alternatively, homologation of the ester of cis-5-pyridinylproline and conversion to bromide allowed cyclization to the 1-pyridinyl-7-azabicyclo[3.2.1]octane analogues.

  DOI：

  10.1021/jo990130u

文献信息

• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES À UTILISER DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：EUROSCREEN SA

  公开号：WO2015078949A1

  公开（公告）日：2015-06-04

  The present invention is directed to compounds of formula (I), useful in treating and/or preventing inflammatory diseases.

  本发明涉及一种化合物，其化学式为(I)，用于治疗和/或预防炎症性疾病。
• [EN] PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERSAS AS AGONISTS OF G- PROTEIN COUPLED RECEPTOR 43 (GPR43)<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES POUR APPLICATION AU TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：EUROSCREEN SA

  公开号：WO2011073376A1

  公开（公告）日：2011-06-23

  The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

  本发明涉及具有式（I）的新化合物，以及它们在治疗和/或预防代谢性疾病中的用途。
• PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS AS AGONISTS OF G-PROTEIN COUPLED RECEPTOR 43 (GPR43)
  申请人：Hoveyda Hamid R.

  公开号：US20130023539A1

  公开（公告）日：2013-01-24

  The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

  本发明涉及式（I）的新化合物及其在治疗和/或预防代谢性疾病方面的应用。
• Substituted pyrrolidines as G-protein coupled receptor 43 agonists
  申请人：Ogeda SA

  公开号：US10017468B2

  公开（公告）日：2018-07-10

  The present invention is directed to a process for the preparation of aryl-pyrrolidine carboxylic acid derivative compounds which are useful in treating metabolic diseases, said process consisting of coupling an aryl-pyrrolidine compound with an aryl carboxylic acid compound followed by alkaline or acidic treatment, hydrogenolysis or treatment with a fluoride of the ester intermediate to afford novel aryl-pyrrolidine carboxylic acid derivative compounds.

  本发明涉及一种用于制备治疗代谢性疾病的芳基吡咯烷羧酸衍生物化合物的工艺，所述工艺包括将芳基吡咯烷化合物与芳基羧酸化合物偶联，然后对酯类中间体进行碱性或酸性处理、氢解或用氟化物处理，以得到新型芳基吡咯烷羧酸衍生物化合物。
• PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERSAS AS AGONISTS OF G- PROTEIN COUPLED RECEPTOR 43 (GPR43)
  申请人：Euroscreen S.A.

  公开号：EP2513053A1

  公开（公告）日：2012-10-24