8-chloro-6-(2-chlorophenyl)-1-(4-methylpiperazino)-4H-s-triazolo<4,3-a>-1,4-benzodiazepine | 89719-71-1

• 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: 8-chloro-6-(2-chlorophenyl)-1-(4-methylpiperazino)-4H-s-triazolo<4,3-a>-1,4-benzodiazepine
• 英文别名: 8-Chloro-1-[(4-methylpiperazino)methyl]-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine；8-chloro-6-(2-chlorophenyl)-1-[(4-methyl-1-piperazinyl)methyl]-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine；8-chloro-6-(2-chlorophenyl)-1-[(4-methylpiperazin-1-yl)methyl]-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
• CAS: 89719-71-1
• 化学式: C₂₂H₂₂Cl₂N₆
• 分子量: 441.363
• InChiKey: VMYJKZHHFBLLOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2',5-dichloro-2-[3-(4-methylpiperazinomethyl)-5(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 8-chloro-6-(2-chlorophenyl)-1-(4-methylpiperazino)-4H-s-triazolo<4,3-a>-1,4-benzodiazepine
  参考文献：
  名称：

  Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][

  摘要：

  一种用于生产化合物的多步骤过程，该化合物的分子式为V：其中R'和R"是1至3个碳原子的烷基，包括或一起；是吡咯烷基、哌啶基、4-甲基哌嗪基或吗啉基；环A和环B未取代，或被来自氟、氯、溴、硝基和三氟甲基的一种或多种取代基取代，该过程包括将式1的化合物的当量与2当量的α-邻苯二甲酰亚胺乙酰卤在惰性有机溶剂中处理，以获得1,3-二氧杂-2-异吲哚乙酸，[[N-(2-苯甲酰基苯基)-1,3-二氧杂-2-异吲哚乙酰胺基]亚甲基]肼II，处理III化合物与三氟乙酸，得到化合物III；将化合物III与惰性有机溶剂中的二烷基亚甲基氯化铵处理，得到2-[3-(二烷基氨基)甲基-5-(邻苯二甲酰基甲基)-4H-1,2,4-三唑-4-基]苯并酮IV，并将IV处理与醇中的肼，得到上述化合物V。还声明了中间体II和IV。1-氨甲基三唑苯二氮杂平(V)化合物用于治疗哺乳动物和鸟类的焦虑和/或抑郁症状。

  公开号：

  US03957761A1

文献信息

• Potential hypnotics and anxiolytics: 8-Chloro-6-(2-chlorophenyl)-1-[4-(2-methoxyethyl)piperazino]-methyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine and related compounds
  作者：Zdeněk Polívka、Jiří Holubek、Jan Metyš、Zdeněk Šedivý、Miroslav Protiva

  DOI：10.1135/cccc19833433

  日期：——

  Ethyl esters of 4-substituted piperazinoacetic acids IIIa-f were prepared by alkylation of 1-(ethoxycarbonylmethyl)piperazine with 2-methoxyethyl bromide, 2-ethoxyethyl bromide, 2-methylthioethyl chloride, 2-phenoxyethyl bromide and 2-phenylthioethyl bromide or by reactions of 1-(3-methoxypropyl)piperazine and 1-(2-methylthioethyl)piperazine with ethyl chloroacetate. Reactions of the esters with hydrazine hydrate gave the hydrazides IVa-f. Their treatment with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-thione resulted in the title compound Ia and analogues Ib-f. 1-(4-Methylpiperazinomethyl) derivatives Ig and IIg were similarly prepared from 4-methylpiperazinoacetic acid hydrazide (IVg). Compound Ig showed significant central depressant and anticonvulsant (electroshock) activity in mice. The enlargement of the substituent in position 4 of the piperazine residue results in an important decrease of these activities.

  4-取代哌嗪基乙酸乙酯IIIa-f通过将1-(乙氧羰基甲基)哌嗪与2-甲氧基乙基溴、2-乙氧基乙基溴、2-甲硫基乙基氯化物、2-苯氧基乙基溴和2-苯硫基乙基溴进行烷基化反应制备，或者通过1-(3-甲氧基丙基)哌嗪和1-(2-甲硫基乙基)哌嗪与氯乙酸乙酯反应制备。这些酯与水合肼反应得到肼酰肼IVa-f。它们与7-氯-5-(2-氯苯基)-1,3-二氢-1,4-苯并二氮杂硫蒽-2-硫酮反应得到标题化合物Ia及类似物Ib-f。1-(4-甲基哌嗪基)衍生物Ig和IIg类似地由4-甲基哌嗪基乙酸肼IVg制备而成。化合物Ig在小鼠中显示出显著的中枢抑制和抗惊厥（电休克）活性。在哌嗪残基的4位上增大取代基会导致这些活性的显著减少。
• POLIVKA, Z.;HOLUBEK, J.;METYS, J.;SEDIVY, Z.;PROTIVA, M., COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 12, 3433-3443
  作者：POLIVKA, Z.、HOLUBEK, J.、METYS, J.、SEDIVY, Z.、PROTIVA, M.

  DOI：——

  日期：——
• US3957761A
  申请人：——

  公开号：US3957761A

  公开（公告）日：1976-05-18
• Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][
  申请人：The Upjohn Company

  公开号：US03957761A1

  公开（公告）日：1976-05-18

  A multistep process for the production of a compound of the formula V: ##SPC1## wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive or together ##EQU1## is pyrrolidino, piperidino, 4-methylpiperazino or morpholino; and wherein the rings A and B are unsubstituted, or substituted by one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro and trifluoromethyl, which comprises treating an equivalent of a compound of formula 1: ##SPC2## Wherein rings A and B are defined as above, with 2 equivalents of an .alpha.-phthalimido acetyl halide in an inert organic solvent to obtain a 1,3-dioxo-2-isoindolineacetic acid, [[N-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamido]methylene]hydrazide II which when treated with trifluoroacetic acid gives compound III; treating compound III with a dialkylmethyleneammonium chloride in an inert organic solvent to obtain a 2-[3-(dialkylamino)methyl-5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benz ophenone IV and treating IV with hydrazine in an alkanol to obtain a compound V above. Also claimed are the intermediates II and IV. The 1-aminomethyltriazolobenzodiazepine compounds (V) are used for treatment of anxieties and/or depressions in mammals and birds.

  一种用于生产化合物的多步骤过程，该化合物的分子式为V：其中R'和R"是1至3个碳原子的烷基，包括或一起；是吡咯烷基、哌啶基、4-甲基哌嗪基或吗啉基；环A和环B未取代，或被来自氟、氯、溴、硝基和三氟甲基的一种或多种取代基取代，该过程包括将式1的化合物的当量与2当量的α-邻苯二甲酰亚胺乙酰卤在惰性有机溶剂中处理，以获得1,3-二氧杂-2-异吲哚乙酸，[[N-(2-苯甲酰基苯基)-1,3-二氧杂-2-异吲哚乙酰胺基]亚甲基]肼II，处理III化合物与三氟乙酸，得到化合物III；将化合物III与惰性有机溶剂中的二烷基亚甲基氯化铵处理，得到2-[3-(二烷基氨基)甲基-5-(邻苯二甲酰基甲基)-4H-1,2,4-三唑-4-基]苯并酮IV，并将IV处理与醇中的肼，得到上述化合物V。还声明了中间体II和IV。1-氨甲基三唑苯二氮杂平(V)化合物用于治疗哺乳动物和鸟类的焦虑和/或抑郁症状。