[(5-methyl-2-oxo)hexyl]triphenylphosphonium bromide | 136604-91-6

• 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: [(5-methyl-2-oxo)hexyl]triphenylphosphonium bromide
• 英文别名: (5-Methyl-2-oxohexyl)-triphenylphosphanium;bromide
• CAS: 136604-91-6
• 化学式: Br*C₂₅H₂₈OP
• 分子量: 455.374
• InChiKey: HIACWLNDCYUDAQ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(5-methyl-2-oxo)hexyl]triphenylphosphonium bromide 在 sodium carbonate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 水 为溶剂， 反应 0.5h， 生成 isoamylcarbonylmethylenetriphenyl phosphorane
  参考文献：
  名称：

  An Efficient and Cost-Effective Synthesis of Pagoclone

  摘要：

  The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2-oxohexyl)-1-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABA(A) receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a beta-keto phosphonium salt was prepared by selectively reacting a primary alpha-bromo ketone with triphenylphosphine in the presence of a secondary alpha-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a gamma-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.

  DOI：

  10.1021/op034060b
• 作为产物：
  描述：

  5-甲基-2-己酮 、 三苯基膦 在 溴 作用下， 以 甲醇 、 甲基叔丁基醚 为溶剂， 反应 12.0h， 以57%的产率得到[(5-methyl-2-oxo)hexyl]triphenylphosphonium bromide
  参考文献：
  名称：

  An Efficient and Cost-Effective Synthesis of Pagoclone

  摘要：

  The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2-oxohexyl)-1-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABA(A) receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a beta-keto phosphonium salt was prepared by selectively reacting a primary alpha-bromo ketone with triphenylphosphine in the presence of a secondary alpha-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a gamma-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.

  DOI：

  10.1021/op034060b

文献信息

• Methods for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone
  申请人：——

  公开号：US20030191315A1

  公开（公告）日：2003-10-09

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)-2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。
• Methods for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2oxo-hexyl)-1-isoidolinone
  申请人：Jennings Marie Sandra

  公开号：US20050288322A1

  公开（公告）日：2005-12-29

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)-2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。
• Method for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone)
  申请人：Jennings Marie Sandra

  公开号：US20060194830A1

  公开（公告）日：2006-08-31

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。
• METHODS OF PREPARATION OF THE 2-(7-CHLORO-1,8-NAPHTHYRIDINE-2-YL)-3-(5-METHYL-2-OXO-HEXYL)-1-ISOINDOLINONE
  申请人：Warner-Lambert Company LLC

  公开号：EP1490363A1

  公开（公告）日：2004-12-29
• US6949653B2
  申请人：——

  公开号：US6949653B2

  公开（公告）日：2005-09-27