4,4’-二氰基二苯溴甲烷 | 69545-39-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4,4’-二氰基二苯溴甲烷
• 中文别名: 4,4'-二氰基二苯溴甲烷；4,4-二氰基二苯基溴甲烷
• 英文名称: 4,4-diphenylcyano dibromomethane
• 英文别名: 4,4'-dicyanodiphenylbromomethane；bromo-bis-(4-cyanophenyl)-methanol；4-(α-bromo-4-cyanobenzyl)benzonitrile；4-[Bromo-(4-cyanophenyl)methyl]benzonitrile
• CAS: 69545-39-7
• 化学式: C₁₅H₉BrN₂
• 分子量: 297.154
• InChiKey: PSGKQDFBVORSNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,4’-二氰基二苯溴甲烷 在 copper(l) iodide 、 sodium azide 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 1-(4,4'-dicyanodiphenylmethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors

  摘要：

  A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole I. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 mu M), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.074
• 作为产物：
  描述：

  对氟苯腈 在 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4,4’-二氰基二苯溴甲烷
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors

  摘要：

  A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole I. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 mu M), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.074

文献信息

• Letrozole production process
  申请人：Friedman Oded

  公开号：US20070112202A1

  公开（公告）日：2007-05-17

  Provided is a method for preparing letrozole, which includes reacting an activated bis-(4-cyanophenyl)-methane with a triazole to produce letrozole, and, optionally, purifying the letrozole. Also provided are highly pure letrozole, and a method of purifying letrozole, which method includes precipitating letrozole, e.g., by selective precipitation from a reaction mixture and/or by subjecting the letrozole to one or more crystallizations.

  提供了一种制备来曲唑的方法，该方法包括将激活的双-(4-氰基苯基)-甲烷与三唑反应以来曲唑，以及可选地纯化来曲唑。还提供了高纯度的来曲唑，以及一种纯化来曲唑的方法，该方法包括沉淀来曲唑，例如通过从反应混合物中选择性沉淀和/或将来曲唑进行一个或多个结晶。
• [EN] AN IMPROVED PROCESS FOR PREPARATION OF LETROZOLE AND ITS INTERMEDIATES<br/>[FR] PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION DU LÉTROZOLE ET SES INTERMÉDIAIRES
  申请人：DABUR PHARMA LTD

  公开号：WO2009069140A1

  公开（公告）日：2009-06-04

  The present invention relates to an improved process for preparation of the non-steroidal aromatase inhibitor drug, Letrozole of formula (I) and its intermediates, 4-[1-(1,2,4-triazolyl) methyl]-benzonitrile of formula (IV) and 4-[1-(1,2,4-triazolyl) methyl]-benzonitrile hydrochloride of formula (VII), all having a purity of ≥99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

  本发明涉及一种改进的制备式(I)的非甾体芳香化酶抑制剂药物来曲唑及其中间体，式(IV)的4-[1-(1,2,4-三唑基)甲基]-苯腈和式(VII)的4-[1-(1,2,4-三唑基)甲基]-苯腈盐酸盐，所有纯度≥99%，该法简单、方便、经济、不使用有害化学品且适合工业生产。
• 一种来曲唑的制备方法
  申请人：浙江工业大学

  公开号：CN105801501A

  公开（公告）日：2016-07-27

  本发明提供了一种来曲唑(6)的制备方法，所述的制备方法为：化合物(1)与化合物(2)在碱性物质的作用下反应得到化合物(3)；化合物(3)经溴化反应得到化合物(4)；化合物(4)与4?氨基?1,2,4?三氮唑(5)缩合，之后重氮化脱除氨基得到来曲唑(6)；本发明方法路线简单，采用廉价易得的对氯苯甲腈和对甲基苯甲腈为起始原料，总共经3步反应得到目标产物来曲唑，本发明制备方法反应条件温和、操作简便、收率高、化学选择性好、生产成本低，适合工业化生产，具有较大的实际应用价值和社会经济效益。
• PROCESS FOR PREPARATION OF LETROZOLE AND ITS INTERMEDIATES
  申请人：Shrawat Vimal Kumar

  公开号：US20100234617A1

  公开（公告）日：2010-09-16

  The present invention relates to an improved process for preparation of the non-steroidal aromatase inhibitor drug, Letrozole of formula (I) and its intermediates, 4-[1-(1,2,4-triazolyl)methyl]-benzonitrile of formula (IV) and 4-[1-(1,2,4-triazolyl)methyl]-benzonitrile hydrochloride of formula (VII), all having a purity of ≧99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

  本发明涉及一种改进的非甾体芳香化酶抑制剂药物Letrozole的制备工艺，以及其中间体4-[1-(1,2,4-三唑基)甲基]-苯甲腈的制备工艺，以及4-[1-(1,2,4-三唑基)甲基]-苯甲腈盐酸盐的制备工艺，它们的纯度均≧99%，该工艺简单、方便、经济、不使用有害化学品且具有工业可行性。
• 一种合成来曲唑的方法
  申请人：蚌埠丰原医药科技发展有限公司

  公开号：CN102070542A

  公开（公告）日：2011-05-25

  本发明公开了一种合成来曲唑的方法，包括下述步骤：1)先合成中间体I，4，4′-氰基二苯基甲烷；2)然后使用催化剂使中间体I发生溴代反应得到中间体II 4-(α-溴代-4-氰基)苯甲腈；3)最后使中间体II与1，2，4-三氮唑进行缩合生成来曲唑粗品，进行重结晶。该方法易于得到高纯度产品，反应条件温和、经济、适合大规模生产。