7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine | 112393-62-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine
• 英文别名: 7-Chlor-2-hydrazino-5-phenyl-3H-1,4-benzodiazepin；7-chloro-5-phenyl-3H-1,4-benzodiazepin-2-yl hydrazine；(7-chloro-5-phenyl-3H-1,4-benzodiazepin-2-yl)hydrazine
• CAS: 112393-62-1
• 化学式: C₁₅H₁₃ClN₄
• 分子量: 284.748
• InChiKey: GWSXDWFXNVOIIC-UHFFFAOYSA-N

物化性质

• 沸点：
  440.4±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  62.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine 在 tetrabutylammonium tetrafluoroborate 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 生成 阿普唑仑
  参考文献：
  名称：

  1,2,4-三唑稠合杂环的电化学合成

  摘要：

  在温和的电解条件下已开发出无试剂的分子内脱氢C–N交叉偶联反应。在这种原子经济和一步经济的一锅法中，有价值的1,2,4-三唑并[4,3- a ]吡啶和相关的杂环化合物可以从可商购的脂族或（杂）芳族醛和2-肼基吡啶。各种官能团都与这种无金属和无氧化剂的方案兼容，可以轻松地以克为单位进行操作。这种新方法被应用于最畅销药物Xanax的合成和后期功能化，以在生物学相关的先导分子中产生化学多样性。

  DOI：

  10.1039/c7gc03739b
• 作为产物：
  描述：

  2-amino-7-chloro-5-phenyl-3H-1,4-benzodiazepine dihydrochloride 在 一水合肼 作用下， 以 甲醇 为溶剂， 生成 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine
  参考文献：
  名称：

  Benzodiazepine derivatives

  摘要：

  苯二氮䓬类化合物的一般结构式为##STR1##其中R.sub.1为氢或1-8个碳原子的烃基残基，R.sub.2为氢或较低的烷基，环A和环B未取代或被硝基、三氟甲基、卤素、较低烷基或较低烷氧基取代，5-位的氮原子未取代或被氧原子取代，可用作肌肉松弛剂、抗惊厥剂、镇静剂和安定剂，并提供其生产方法。还提供了一般结构式为##STR2##的新中间体，其中R.sub.2具有上述含义，环A和环B未取代或如上所述取代，4-位的氮原子未取代或被氧原子取代。

  公开号：

  US04116956A1

文献信息

• Triazinobenzodiazepines
  申请人：The Upjohn Company

  公开号：US04028356A1

  公开（公告）日：1977-06-07

  Compounds of formula IV: ##STR1## wherein R and R.sub.2 are hydrogen or methyl; wherein R.sub.1 is --COOH, --COOR' in which R' is alkyl of 1 to 3 carbon atoms, inclusive, --(CnH.sub.2 n)A in which n is an integer of 1 to 3 and A is fluoro, chloro, bromo, trifluoromethyl, hydroxy, alkoxy, in which the alkyl group is defined as above, or ##STR2## in which R" and R'" are hydrogen or alkyl as defined above or together ##STR3## is pyrrolidino, piperidino, morpholino, 4-methylpiperazino, 4-(2-hydroxyethyl)-piperazino; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl, or nitro; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, or 2-pyridyl, are produced. The compounds of formula IV of this invention are sedatives, tranquilizers and muscle-relaxants and can be used for such purposes in mammals and birds.

  IV式化合物：##STR1##其中R和R.sub.2为氢或甲基；其中R.sub.1为--COOH，--COOR'，其中R'为1至3个碳原子的烷基，包括，--(CnH.sub.2 n)A，其中n为1至3的整数，A为氟、氯、溴、三氟甲基、羟基、烷氧基，其中烷基团如上所定义，或##STR2##其中R"和R'"为如上所定义的氢或烷基，或一起##STR3##为吡咯啉基、哌啶基、吗啉基、4-甲基哌嗪基、4-(2-羟乙基)-哌嗪基；其中R.sub.3为氢、氟、氯、溴、三氟甲基或硝基；Ar为苯基、邻氯苯基、邻氟苯基、2,6-二氟苯基或2-吡啶基。本发明的IV式化合物是镇静剂、安定剂和肌肉松弛剂，可用于哺乳动物和鸟类。
• 1-(Aminoalkyl)-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with antianxiety and antidepressant activity
  作者：Jackson B. Hester、Allan D. Rudzik、Philip F. Von Voigtlander

  DOI：10.1021/jm00178a009

  日期：1980.4

  A series of 1-(aminoalkyl)-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines has been prepared and evaluated for central nervous system activity. We have found that members of this series have activity in pharmacological test systems designed to detect both anxiolytic and antidepressant activity. Each type of activity could be varied independently by appropriate substituent selections.

  已经制备了一系列的1-（氨基烷基）-6-芳基-4H-s-三唑并[4，3-a] [1，4]苯并二氮杂并评估中枢神经系统活性。我们发现该系列的成员在旨在检测抗焦虑和抗抑郁活性的药理学测试系统中具有活性。每种类型的活性可以通过适当的取代基选择独立地变化。
• 1-Ethanamine-triazolo-benzodiazepines as diuretics
  申请人：The Upjohn Company

  公开号：US04514407A1

  公开（公告）日：1985-04-30

  Triazolo-benzodiazepine-1-ethanamines of the formulas ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Ring A are as defined in the specification, e.g., 8-chloro-N,N-dimethyl-.beta.,6-diphenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benz odiazepine-1-ethanamine, and pharmacologically acceptable salts thereof, have been found to have substantial diuretic, natriuretic, but little, if any, kaliuretic activity, which can be used alone, or concomittently with other diuretic drugs such as furosemide or hydrochlorothiazide and/or with antihypertensive agents such as propranolo, captopril, minoxidil, prazosin, guanadrel sulfate, whose actions are supplemented by the action of a diuretic drug.

  Triazolo-苯二氮卓-1-乙胺的分子式为##STR1##其中R、R.sub.1、R.sub.2、R.sub.3、R.sub.4和环A如规范中所定义，例如8-氯-N，N-二甲基-β，6-二苯基-4H-[1,2,4]三唑并[4,3-a][1,4]苯二氮卓-1-乙胺及其药理学上可接受的盐，已被发现具有显著的利尿、排钠作用，但几乎没有钾排泄作用，可单独使用，或与其他利尿药物如呋塞米或氢氯噻嗪以及/或抗高血压药物如普萘洛尔、卡普托普利、米诺地尔、普拉唑辛、瓜那德雷酸盐同时使用，其作用被利尿药物的作用所补充。
• 1-Halomethyl-6-phenyl-4H-s-[4,3-a][1,4]benzodiazepines
  申请人：The Upjohn Company

  公开号：US04141902A1

  公开（公告）日：1979-02-27

  1-Substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula II: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, methyl, ethyl, fluorine, chlorine, and bromine, and X is selected from fluorine, chlorine, and bromine; wherein R.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms inclusive; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl, as defined above, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, and alkylsulfonyl, in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are prepared by reacting a compound of the formula: ##STR2## wherein R.sub.1, R.sub.2, R.sub.3 R.sub.4, and R.sub.5 are defined as above, with an haloacyl chloride or haloacyl bromide of the formula ##STR3## wherein R.sub.o and X are defined as above and X' is chlorine or bromine. The new products of formula II including their pharmacologically acceptable acid addition salts are useful as sedatives, tranquilizers and muscle relaxants in mammals and birds, and if X.dbd.X".dbd.Cl or Br they are useful as intermediates for cyano, alkylthio and dialkylamino products of high sedative and tranquilizing activity.

  式II的1-取代-6-苯基-4H-s-三唑并[4,3-a][1,4]苯二氮杂环戊烷化合物：其中R.sub.0从氢、甲基、乙基、氟、氯和溴组成的群体中选择，X从氟、氯和溴中选择；其中R.sub.1从氢、1至3个碳原子的包括的烷基中选择；其中R.sub.2、R.sub.3、R.sub.4和R.sub.5从氢、如上定义的烷基、卤素、硝基、氰基、三氟甲基和烷氧基、烷硫基、烷硫醇基和烷磺酰基组成的群体中选择，其中碳链基团为1至3个碳原子，包括，通过将式化合物反应得到：其中R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5如上定义，与式卤代酰氯或卤代酰溴反应得到：其中R.sub.o和X如上定义，X'为氯或溴。包括其药理学上可接受的酸盐的式II的新产物可用作哺乳动物和鸟类的镇静剂、安定剂和肌肉松弛剂，如果X.dbd.X".dbd.Cl或Br，则它们可用作具有高镇静和安定活性的氰基、烷硫基和二烷基胺产物的中间体。
• Triazino benzodiazepines
  申请人：The Upjohn Company

  公开号：US04016165A1

  公开（公告）日：1977-04-05

  Compounds of formula IV: ##STR1## wherein R and R.sub.1 are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen or methyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl or nitro; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl or 2-pyridyl, are produced by reacting a hydrazino compound of the formula I ##STR2## wherein R.sub.2, R.sub.3, and Ar are defined as above, with a carbonyl reagent of the formula II: ##STR3## wherein R and R.sub.1 are defined as above and Y is chloro, bromo, iodo or --O--SO.sub.2 --R.sub.4 in which R.sub.4 is alkyl, defined as above, phenyl, or tolyl, to give the compound III: ##STR4## wherein R, R.sub.1, R.sub.2, R.sub.3, Ar, and Y are defined as above and heating compound III, in an inert organic solvent, to give compound IV above. The compounds of formula IV of this invention and the pharmacologically acceptable acid addition salts thereof are sedatives, tranquilizers and muscle-relaxants and can be used for such purposes in mammals and birds.

  根据上述描述，公式IV的化合物如下所示：其中R和R.sub.1为氢或1至3个碳原子的烷基；其中R.sub.2为氢或甲基；其中R.sub.3为氢、氟、氯、溴、三氟甲基或硝基；Ar为苯基、邻氯苯基、邻氟苯基、2,6-二氟苯基或2-吡啶基，通过将公式I的肼基化合物与公式II的羰基试剂反应而制备：其中R.sub.2、R.sub.3和Ar如上所述，公式II的羰基试剂如下：其中R和R.sub.1如上所述，Y为氯、溴、碘或--O--SO.sub.2 --R.sub.4，其中R.sub.4为烷基、苯基或甲苯基，得到化合物III：其中R、R.sub.1、R.sub.2、R.sub.3、Ar和Y如上所述，将化合物III在惰性有机溶剂中加热，得到上述的化合物IV。本发明的公式IV的化合物及其药理学可接受的酸盐为镇静剂、安定剂和肌肉松弛剂，可用于哺乳动物和鸟类。