7-fluoro-N-(2-fluorophenyl)-1,2,3,5-tetrahydro-3-oxopyrido[1,2-a]benzimidazole-4-carboxamide | 155202-16-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 7-fluoro-N-(2-fluorophenyl)-1,2,3,5-tetrahydro-3-oxopyrido[1,2-a]benzimidazole-4-carboxamide
• 英文别名: 7-fluoro-N-(2-fluorophenyl)-3-oxo-2,5-dihydro-1H-pyrido[1,2-a]benzimidazole-4-carboxamide
• CAS: 155202-16-7
• 化学式: C₁₈H₁₃F₂N₃O₂
• 分子量: 341.317
• InChiKey: VHGHHWZFWJWYEZ-UHFFFAOYSA-N

物化性质

• 沸点：
  493.4±45.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61.44
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-甲氧基乙氧基甲基氯 、 7-fluoro-N-(2-fluorophenyl)-1,2,3,5-tetrahydro-3-oxopyrido[1,2-a]benzimidazole-4-carboxamide 在 15-冠醚-5 、 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 42.0h， 生成 7-Fluoro-1,2-dihydro-5-[2-(methoxy)ethoxymethyl]-3-oxo-N-(2-fluorophenyl)pyrido[1,2-a]benzimidazole-4-carboxamide
  参考文献：
  名称：

  5-HETEROATOM-CONTAINING ALKYL SUBSTITUTED-3-OXO-PYRIDO(1,2-a) BENZIMIDAZOLE-4-CARBOXAMIDE DERIVATIVES USEFUL IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS

  摘要：

  公开号：

  EP0935598B1
• 作为产物：
  描述：

  4-氟-2-硝基苯胺 在 盐酸 、 palladium on activated charcoal 、 氢气 、 sodium ethanolate 、 苄基三甲基氢氧化铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 7-fluoro-N-(2-fluorophenyl)-1,2,3,5-tetrahydro-3-oxopyrido[1,2-a]benzimidazole-4-carboxamide
  参考文献：
  名称：

  Process Research for the Synthesis of RWJ-51204, A Novel Anxiolytic Agent

  摘要：

  RWJ-51204, the lead compound in our pyrido [1,2-a] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and clinical studies, we needed to develop a safe and scaleable synthesis, Our main focus was to improve the last two steps of the process which involved formation of the penultimate carboxamide intermediate followed by alkylation using potentially toxic chloromethyl ethyl ether. Due to safety issues concerning storage and handling of this reagent during the large scale synthesis, we investigated alternate routes to minimize potential exposure risks. The process research carried out for the final steps that led to the safe and cost-effective multi-kilogram synthesis of RWJ-51204 is described herein.

  DOI：

  10.1021/op990182l

文献信息

• Potential Anxiolytic Agents. Part 4: Novel Orally-Active N5-Substituted Pyrido[1,2-a]benzimidazoles with High GABA-A Receptor Affinity
  作者：Alfonzo D Jordan、Anil H Vaidya、Daniel I Rosenthal、Barry Dubinsky、Cheryl P Kordik、Pauline J Sanfilippo、Wu-Nan Wu、Allen B Reitz

  DOI：10.1016/s0960-894x(02)00463-8

  日期：2002.9

  A series of pyrido[1,2-a]benzimidazoles (PBIs) with substitution on the N-5-nitrogen has been synthesized and found to possess high affinity for the benzodiazepine (BZD) site on the GABA-A receptor. The compounds evaluated include those bearing a heteroalkyl group and heterocyclic rings. The most promising of these compounds is ethoxymethyl analogue 24, which has an IC50 of 0.1 nM for the BZD site on the GABA-A receptor and has been advanced to human clinical trials. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Process Research for the Synthesis of RWJ-51204, A Novel Anxiolytic Agent
  作者：Judith H. Cohen、Cynthia A. Maryanoff、Stephen M. Stefanick、Kirk L. Sorgi、Frank J. Villani

  DOI：10.1021/op990182l

  日期：1999.7.1

  RWJ-51204, the lead compound in our pyrido [1,2-a] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and clinical studies, we needed to develop a safe and scaleable synthesis, Our main focus was to improve the last two steps of the process which involved formation of the penultimate carboxamide intermediate followed by alkylation using potentially toxic chloromethyl ethyl ether. Due to safety issues concerning storage and handling of this reagent during the large scale synthesis, we investigated alternate routes to minimize potential exposure risks. The process research carried out for the final steps that led to the safe and cost-effective multi-kilogram synthesis of RWJ-51204 is described herein.
• 5-HETEROATOM-CONTAINING ALKYL SUBSTITUTED-3-OXO-PYRIDO(1,2-a) BENZIMIDAZOLE-4-CARBOXAMIDE DERIVATIVES USEFUL IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP0935598B1

  公开（公告）日：2003-12-10