(4,5-二氢-2-甲基咪唑并[4,5-d][1]苯并氮杂卓-6(1H)-基)(4-硝基苯基)甲酮 | 168626-71-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: (4,5-二氢-2-甲基咪唑并[4,5-d][1]苯并氮杂卓-6(1H)-基)(4-硝基苯基)甲酮
• 中文别名: (4,5-二氢-2-甲基咪唑并[4,5-D][1]苯并氮杂卓-6(1H)-基)(4-硝基苯基)甲酮；(2-甲基-4,5-二氢苯并[b]咪唑并[4,5-d]氮杂革、-6(1h)-基)(4-硝基苯基)甲酮
• 英文名称: 2-methyl-6-(4-nitrobenzoyl)-1,4,5,6-tetrahydroimidazo-[4,5-d][1]benzazepine
• 英文别名: 6-(4-nitrobenzoyl)-2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine；(2-Methyl-4,5-dihydrobenzo[b]imidazo[4,5-d]azepin-6(1H)-yl)(4-nitrophenyl)methanone；(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepin-6-yl)-(4-nitrophenyl)methanone
• CAS: 168626-71-9
• 化学式: C₁₉H₁₆N₄O₃
• 分子量: 348.361
• InChiKey: GKKPPENORPTEJV-UHFFFAOYSA-N

物化性质

• 沸点：
  694.2±55.0 °C(Predicted)
• 密度：
  1.384

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (4,5-二氢-2-甲基咪唑并[4,5-d][1]苯并氮杂卓-6(1H)-基)(4-硝基苯基)甲酮 在 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以94%的产率得到{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl}amine
  参考文献：
  名称：

  Practical Synthesis of N-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin- 6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride:  an Arginine Vasopressin Antagonist

  摘要：

  A novel, reliable, and cost-effective synthetic route to N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]-phenyl}biphenyl-2-carboxamide monohydrochloride (1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole formation from alpha-bromoketone furnished imidazobenzazepine, avoiding potential oxazole-ring formation. Catalytic reduction of nitro imidazobenzazepine afforded the corresponding amine in high yields. Treatment of the imidazole-containing amine directly, with a carbonyl chloride, afforded the target amide circumventing protection of the imidazole.

  DOI：

  10.1021/op034079e
• 作为产物：
  描述：

  1-[(4-methylphenyl)sulfonyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carbonitrile 在 盐酸 、 溴 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 31.0h， 生成 4-bromo-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one 、 (4,5-二氢-2-甲基咪唑并[4,5-d][1]苯并氮杂卓-6(1H)-基)(4-硝基苯基)甲酮
  参考文献：
  名称：

  Practical Synthesis of N-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin- 6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride:  an Arginine Vasopressin Antagonist

  摘要：

  A novel, reliable, and cost-effective synthetic route to N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]-phenyl}biphenyl-2-carboxamide monohydrochloride (1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole formation from alpha-bromoketone furnished imidazobenzazepine, avoiding potential oxazole-ring formation. Catalytic reduction of nitro imidazobenzazepine afforded the corresponding amine in high yields. Treatment of the imidazole-containing amine directly, with a carbonyl chloride, afforded the target amide circumventing protection of the imidazole.

  DOI：

  10.1021/op034079e

文献信息

• Condensed benzazepine derivative and pharmaceutical composition thereof
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05723606A1

  公开（公告）日：1998-03-03

  This invention relates to nitrogen-containing aromatic 5-membered ring-condensed benzazepine derivatives represented by the general formula (I) ##STR1## (symbols in the formula have the following meanings; ring B: a nitrogen-containing aromatic 5-membered ring having at least 1 nitrogen atom and optionally one oxygen or sulfur atom, which may optionally have substituent(s), R.sup.1 and R.sup.2 : these may be the same or different from each other and each represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group which may optionally be substituted by lower alkyl group(s), or a lower alkoxy group, A: a single bond; a group represented by the formula --NHCO--(CR.sup.3 R.sup.4).sub.n --, n: 0 or an integer of from 1 to 3, R.sup.3 and R.sup.4 : these may be the same or different from each other and each represents a hydrogen atom, a lower alkyl group (provided that R.sup.3 and R.sup.4 may together form a lower alkylene group having 2 to 7 carbon atoms), and ring C: a benzene ring which may optionally have substituent(s)) and salts thereof; to pharmaceutical compositions which contain these compounds as an active ingredient and to intermediates which are useful in synthesizing these compounds. The compounds of this invention are useful as arginine vasopressin antagonists.

  这项发明涉及一般式(I)所代表的含氮芳香5-成员环-融合苯并哌嗪衍生物，其中##STR1##（式中符号的含义如下；环B：至少含有1个氮原子且可能有一个氧原子或硫原子的含氮芳香5-成员环，可以选择地具有取代基，R.sup.1和R.sup.2：它们可以相同也可以不同，每个代表氢原子、卤素原子、低烷基、可能被低烷基取代的氨基或低烷氧基，A：单键；一个由式--NHCO--(CR.sup.3 R.sup.4).sub.n --表示的基团，n：0或1至3的整数，R.sup.3和R.sup.4：它们可以相同也可以不同，每个代表氢原子、低烷基（条件是R.sup.3和R.sup.4可以一起形成具有2至7个碳原子的低烷基烯基），环C：可能具有取代基的苯环）及其盐；含有这些化合物作为活性成分的药物组合物；以及在合成这些化合物中有用的中间体。本发明的化合物可用作精氨酸加压素拮抗剂。
• Intermediate for condensed benzazepine derivatives
  申请人：YAMANOUCHI PHARMACEUTICAL CO., LTD.

  公开号：EP1097920A1

  公开（公告）日：2001-05-09

  (Biphenyl-2-ylcarboxamide)benzoic acid is useful on an intermediate for the synthesis of condensed benzazepine derivatives which are arginine vasopressin antagonists.

  (联苯-2-甲酰胺）苯甲酸是合成精氨酸加压素拮抗剂缩合苯并氮杂卓衍生物的中间体。
• Drugs. Fut. 2000, 25, 1121-1130
  作者：

  DOI：——

  日期：——
• FUSED BENZAZEPINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0709386B1

  公开（公告）日：2003-05-07