(S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)-2’-oxo-1‘,2’,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3‘-pyrrolo [2,3-b]pyridine]-3-carboxamide | 1374248-83-5

• 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: (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)-2’-oxo-1‘,2’,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3‘-pyrrolo [2,3-b]pyridine]-3-carboxamide
• 英文别名: (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)-2’-oxo-1’,2’,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3’-pyrrolo[2,3-b]pyridine]-3-carboxamide；(6S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide；US9833448, Example 5；(3S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide
• CAS: 1374248-83-5
• 化学式: C₂₉H₂₃F₆N₅O₃
• 分子量: 603.524
• InChiKey: OVTQOOXOGJZWCA-CJFQSICBSA-N

物化性质

• 沸点：
  703.0±60.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3-二溴-5-氯吡啶 在 咪唑 、 N-甲基吡咯烷酮 、 盐酸 、 sodium tetrahydroborate 、 氯化亚砜 、 isopropyl magnesium chloride - lithium chloride complex 、 一氧化碳 、 (1S,2R,4S,5R)-1-(2-bromo-5-methoxybenzyl)-2-((S)-(1-(2-bromo-5-methoxybenzyl)-6-methoxyquinolin-1-ium-4-yl)(hydroxy)methyl)-5-vinylquinuclidin-1-ium bromide 、 1,3-双(二环己基磷)丙烷 、 四丁基氟化铵 、 palladium diacetate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， -40.0~120.0 ℃ 、689.49 kPa 条件下， 反应 114.83h， 生成 (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)-2’-oxo-1‘,2’,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3‘-pyrrolo [2,3-b]pyridine]-3-carboxamide
  参考文献：
  名称：

  Process for Making CGRP Receptor Antagonists

  摘要：

  这项发明涵盖了一种制备哌啶酮羧酰胺茚烷和氮杂茚衍生物的新工艺，这些衍生物是CGRP受体拮抗剂，可用于治疗偏头痛。

  公开号：

  US20160130273A1

文献信息

• PIPERIDINONE CARBOXAMIDE AZAINDANE CGRP RECEPTOR ANTAGONISTS
  申请人：Bell Ian M.

  公开号：US20120122899A1

  公开（公告）日：2012-05-17

  The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及哌啶酮羧酰胺吖啶衍生物，它们是CGRP受体拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗CGRP参与的这类疾病中使用这些化合物和组合物。
• [EN] PROCESS FOR MAKING CGRP RECEPTOR ANTAGONISTS<br/>[FR] PROCÉDÉ DE FABRICATION D'ANTAGONISTES DE RÉCEPTEURS DU CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169348A1

  公开（公告）日：2013-11-14

  The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migrane. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.

  该披露涵盖了一种用于制备哌啶酮羧酰胺茚和氮杂茚衍生物的新型过程，与以往的合成方法相比，该过程步骤更少，产率更高。这些化合物是CGRP受体拮抗剂，可用于治疗偏头痛。酰胺键形成的条件包括例如将化合物B（盐断裂后）和C与酰胺偶联试剂以及可选的添加剂和酸和/或碱在非反应性溶剂中反应。
• [EN] PIPERIDINONE CARBOXAMIDE AZAINDANE CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR CGRP DE PIPÉRIDINONE CARBOXAMIDE AZAINDANE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012064910A1

  公开（公告）日：2012-05-18

  The present invention is directed to piperidinone carboxamide azaindane derivatives of formula I which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及公式I的哌啶酮羧酰胺氮杂吲哚衍生物，其是CGRP受体拮抗剂，用于治疗或预防CGRP参与的疾病，如偏头痛。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物和组合物预防或治疗CGRP参与的疾病。
• PROCESS FOR MAKING CGRP RECEPTOR ANTAGONISTS
  申请人：Merck Sharp & Dohme

  公开号：US20150112067A1

  公开（公告）日：2015-04-23

  The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migraine. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.

  该披露涵盖了一种制备哌啶酮羧酰胺吲哚和氮杂吲哚衍生物的新工艺，与以前用于制备这些化合物的合成方法相比，该工艺步骤更少且产率更高，这些化合物是CGRP受体拮抗剂，可用于治疗偏头痛。酰胺键形成的条件包括例如将公式B（盐断后）和C的化合物与酰胺偶联试剂以及非反应性溶剂中的可选添加剂和酸和/或碱反应。
• Piperidinone carboxamide azaindane CGRP receptor antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2821407A1

  公开（公告）日：2015-01-07

  The present invention is directed to piperidinone carboxamide azaindane derivatives of formula I which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及式 I 的哌啶酮羧酰胺氮杂茚衍生物，其是 CGRP 受体的拮抗剂，可用于治疗或预防 CGRP 所涉及的疾病，如偏头痛。本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗CGRP参与的此类疾病中的用途。