2'-甲基-4'-(2-氧代-1-吡咯烷基)-4-联苯基羧酸 | 197450-40-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2'-甲基-4'-(2-氧代-1-吡咯烷基)-4-联苯基羧酸
• 英文名称: 2'-methyl-4'-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid
• 英文别名: SB-251475；2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carboxylic acid；2'-Methyl-4'-(2-oxopyrrolidin-1-yl)[1,1'-biphenyl]-4-carboxylic acid；4-[2-methyl-4-(2-oxopyrrolidin-1-yl)phenyl]benzoic acid
• CAS: 197450-40-1
• 化学式: C₁₈H₁₇NO₃
• 分子量: 295.338
• InChiKey: UCYCSNQPYZDKBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2'-甲基-4'-(2-氧代-1-吡咯烷基)-4-联苯基羧酸 生成 5-[2'-Methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-(1-azabicyclo[3.3.1]nonane)]
  参考文献：
  名称：

  Spiroazabicyclic compounds, processes for their preparation, and their

  摘要：

  本发明揭示了新型的杂环脂环衍生物，其制备方法，含有它们的制药组合物以及它们作为药物的用途。

  公开号：

  US06156783A1
• 作为产物：
  描述：

  4-溴-3-甲基苯胺 在 盐酸 、 palladium on activated charcoal 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 9.0h， 生成 2'-甲基-4'-(2-氧代-1-吡咯烷基)-4-联苯基羧酸
  参考文献：
  名称：

  Multikilogram-Scale Synthesis of a Biphenyl Carboxylic Acid Derivative Using a Pd/C-Mediated Suzuki Coupling Approach

  摘要：

  Reaction of 4-bromo-3-methylanaine with 4-chlorobutyryl chloride/TEA and subsequent treatment of the resulting secondary amide intermediate with KOt-Bu gives 1-(4-bromo-3-methylphenyl)pyrrolidin-2-one in 65% yield, This procedure has been optimised (74-76% overall yield) and has been carried out on 41 molar scale. In a variation of this process, we have employed NaOH as the ring-closing base under phase-transfer conditions, NaOH is added to a mixture of 4-bromo-3-methylaniline, 4-chlorobutyryl chloride, and catalytic TBAC in THF/ H2O, A further 2 equiv of aqueous NaOH is added, and the mixture is heated at 40-45 degrees C, providing access to cyclised product In an improved 86% yield. 1-(4-Bromo-3-methylphenyl)pyrrolidin-2-one is subsequently coupled with 4-carboxyphenylboronic acid under standard Suzuki coupling conditions [Pd(PPh3)(4), Na2CO3, DME/H2O] to give 2'-methyl-4'-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid in 64% yield, contaminated with 40-80 ppm of residual Pd, In a modification of this process, we have used Pd/C as the catalyst, Reaction in MeOH/ H2O gives an improved yield of the biphenylcarboxyiic acid with residual Pd levels of <6 ppm, This process has been carried out on 24 molar scale, The synthesis of the arylpyrrolidinone and subsequent Suzuki coupling have been combined into a one-pot procedure, providing access to 2'-methyl-4'-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid in 82% overall yield from 4-bromo-3-methylaniline.

  DOI：

  10.1021/op980079g

文献信息

• Tetracyclic spiro compounds as 5HT.sub.1B receptor antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US06100272A1

  公开（公告）日：2000-08-08

  Compounds of formula(I) where B is oxygen or sulphur, D is nitrogen, R.sup.6 and R.sup.7 forms a ring, m is 2, R is a substituted latam ring of formula (i) ##STR1## where p is 1, P is a substituted or unsubstituted bicyclic ring containing one or two heteroatoms or P is an unsbustituted or substituted 5- to 7-memebered saturated ring containing one or two heteroatoms; X, Y, Z, E, G, R.sup.3, R.sup.4, R.sup.5, R.sup.8, R.sup.9, and R.sup.10 are as defined in the specification.

  化合物的化学式(I)，其中B为氧或硫，D为氮，R.sup.6和R.sup.7形成一个环，m为2，R为公式(i)的取代的拉丹环：##STR1## 其中p为1，P为含有一个或两个杂原子的取代或未取代的双环环或P为未取代或取代的含有一个或两个杂原子的5-至7-成员饱和环；X、Y、Z、E、G、R.sup.3、R.sup.4、R.sup.5、R.sup.8、R.sup.9和R.sup.10如规范所定义。
• PIPERIDINE DERIVATIVES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0888358A1

  公开（公告）日：1999-01-07
• AZASPIRO DERIVATIVES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0889892A1

  公开（公告）日：1999-01-13
• SPIROAZABICYCLIC COMPOUNDS, PROCESSES FOR THEIR PREPARATION, AND THEIR PHARMACEUTICAL USE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0900221A1

  公开（公告）日：1999-03-10
• US6100272A
  申请人：——

  公开号：US6100272A

  公开（公告）日：2000-08-08