2-[(4,6-difluoro-1H-benzimidazol-2-yl)-difluoromethyl]-3-methylbenzimidazole-5-carboxylic acid | 903898-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-[(4,6-difluoro-1H-benzimidazol-2-yl)-difluoromethyl]-3-methylbenzimidazole-5-carboxylic acid
• CAS: 903898-37-3
• 化学式: C₁₇H₁₀F₄N₄O₂
• 分子量: 378.286
• InChiKey: KXRVTAGGFAPXLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[(4,6-difluoro-1H-benzimidazol-2-yl)-difluoromethyl]-3-methylbenzimidazole-5-carboxylic acid 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 CRA-9249
  参考文献：
  名称：

  Development of a scalable synthesis of a nonbasic inhibitor of the serine protease tryptase

  摘要：

  A chromatography-free process for the synthesis of a bis(benzimidazole)difluoromethane inhibitor of the serine protease tryptase is described. This synthesis features the introduction of the cm-difluoro moiety using the electrophilic fluorinating reagent N-fluoro-bis(phenylsulfonimide) as well as the stepwise introduction of both benzimidazole rings. A protocol for the destruction of reactive, process-related substances produced in the synthesis is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.04.149
• 作为产物：
  描述：

  ethyl 2-(4,6-difluoro-1H-benzimidazol-2-yl)acetate 在 N,N-二甲基丙烯基脲 、 air 、 N-氟代双苯磺酰胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-[(4,6-difluoro-1H-benzimidazol-2-yl)-difluoromethyl]-3-methylbenzimidazole-5-carboxylic acid
  参考文献：
  名称：

  Development of a scalable synthesis of a nonbasic inhibitor of the serine protease tryptase

  摘要：

  A chromatography-free process for the synthesis of a bis(benzimidazole)difluoromethane inhibitor of the serine protease tryptase is described. This synthesis features the introduction of the cm-difluoro moiety using the electrophilic fluorinating reagent N-fluoro-bis(phenylsulfonimide) as well as the stepwise introduction of both benzimidazole rings. A protocol for the destruction of reactive, process-related substances produced in the synthesis is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.04.149

文献信息

• Identification of metabolites of the tryptase inhibitor CRA-9249: Observation of a metabolite derived from an unexpected hydroxylation pathway
  作者：Walter Yu、Jeffrey M. Dener、Daniel A. Dickman、Paul Grothaus、Yun Ling、Liang Liu、Chris Havel、Kimberly Malesky、Tania Mahajan、Colin O’Brian、Emma J. Shelton、David Sperandio、Zhiwei Tong、Robert Yee、Joyce J. Mordenti

  DOI：10.1016/j.bmcl.2006.05.003

  日期：2006.8

  The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process. (c) 2006 Elsevier Ltd. All rights reserved.