1-[3-(1-methylbenzimidazol-2-yl)phenyl]piperidine-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-[3-(1-methylbenzimidazol-2-yl)phenyl]piperidine-4-carboxylic acid
• 化学式: C₂₀H₂₁N₃O₂
• 分子量: 335.406
• InChiKey: CYZQIPUEGFRZPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 1-[3-(1-methylbenzimidazol-2-yl)phenyl]piperidine-4-carboxylic acid 在 N,N'-羰基二咪唑 、 氢溴酸 作用下， 以 乙腈 、 水 为溶剂， 反应 6.5h， 以71%的产率得到{1-[3-(1-methylbenzimidazol-2-yl)phenyl]piperidin-4-yl}-(4-methypiperazin-1-yl)methanone hydrobromide
  参考文献：
  名称：

  A Scalable Route to the SMO Receptor Antagonist SEN826: Benzimidazole Synthesis via Enhanced in Situ Formation of the Bisulfite–Aldehyde Complex

  摘要：

  A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite-aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.

  DOI：

  10.1021/op4002092
• 作为产物：
  描述：

  N-甲基-1,2-苯二胺 在 水 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium hydrogensulfite 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 23.33h， 生成 1-[3-(1-methylbenzimidazol-2-yl)phenyl]piperidine-4-carboxylic acid
  参考文献：
  名称：

  A Scalable Route to the SMO Receptor Antagonist SEN826: Benzimidazole Synthesis via Enhanced in Situ Formation of the Bisulfite–Aldehyde Complex

  摘要：

  A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite-aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.

  DOI：

  10.1021/op4002092

文献信息

• [EN] HEDGEHOG PATHWAY ANTAGONISTS AND THERAPEUTIC APPLICATIONS THEREOF<br/>[FR] ANTAGONISTES DE LA VOIE HEDGEHOG ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：SIENA BIOTECH SPA

  公开号：WO2010142426A1

  公开（公告）日：2010-12-16

  Heterocyclic compounds that modulate the hedgehog signaling pathway, pharmaceutical composition thereof and their therapeutic applications.

  调节刺猬信号通路的杂环化合物，以及其药用组合物和治疗应用。
• HEDGEHOG PATHWAY ANTAGONISTS AND THERAPEUTIC APPLICATIONS THEREOF
  申请人：Thomas J. Russell

  公开号：US20120088752A1

  公开（公告）日：2012-04-12

  Heterocyclic compounds that modulate the hedgehog signaling pathway, pharmaceutical composition thereof and their therapeutic applications.

  杂环化合物，可调节刺猬信号通路，其制药组合物及其治疗应用。
• US8835648B2
  申请人：——

  公开号：US8835648B2

  公开（公告）日：2014-09-16
• A Scalable Route to the SMO Receptor Antagonist SEN826: Benzimidazole Synthesis via Enhanced in Situ Formation of the Bisulfite–Aldehyde Complex
  作者：Matteo Betti、Eva Genesio、Guido Marconi、Salvatore Sanna Coccone、Paul Wiedenau

  DOI：10.1021/op4002092

  日期：2014.6.20

  A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite-aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.