5-氯-3-(环己基甲基)-1H-苯并咪唑-2-酮 | 161469-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 5-氯-3-(环己基甲基)-1H-苯并咪唑-2-酮
• 英文名称: 5-Chloro-3-cyclohexylmethyl-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: 2H-Benzimidazol-2-one, 6-chloro-1-(cyclohexylmethyl)-1,3-dihydro-；5-chloro-3-(cyclohexylmethyl)-1H-benzimidazol-2-one
• CAS: 161469-17-6
• 化学式: C₁₄H₁₇ClN₂O
• 分子量: 264.755
• InChiKey: MCNHWLILAIRSOX-UHFFFAOYSA-N

物化性质

• 熔点：
  183-184 °C
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  2-羟基苯并咪唑 在 4-二甲氨基吡啶 、 sodium hydroxide 、 磺酰氯 、 potassium carbonate 、 异丙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 溶剂黄146 、 乙腈 为溶剂， 反应 2.58h， 生成 5-氯-3-(环己基甲基)-1H-苯并咪唑-2-酮
  参考文献：
  名称：

  Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives

  摘要：

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.

  DOI：

  10.1021/jo00111a014

文献信息

• 1-benzenesulfonyl-1,3-dihydro-2H-benzimidazol-2-one derivatives
  申请人：Sanofi

  公开号：US05585394A1

  公开（公告）日：1996-12-17

  The present invention relates to 1-benzenesulfonyl-1,3-dihydro-2H-benzimidazol-2-one derivatives of the formula: ##STR1## to their preparation and to the pharmaceutical compositions in which they are present. These derivatives have an affinity for the vasopressin and oxytocin receptors.

  本发明涉及1-苯磺酰基-1,3-二氢-2H-苯并咪唑-2-酮衍生物的公式如下：##STR1## 以及它们的制备方法和它们所在的药物组合物。这些衍生物对利尿素和催产素受体具有亲和力。
• Dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, les compositions pharmaceutiques en contenant
  申请人：SANOFI

  公开号：EP0636614A1

  公开（公告）日：1995-02-01

  La présente invention concerne des dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one de formule : leur préparation et les compositions pharmaceutiques en contenant. Ces composés ont une affinité pour les récepteurs de la vasopressine et de l'ocytocine.

  本发明涉及式.1-苯磺酰基-1,3-二氢-2H-苯并咪唑-2-酮衍生物： 及其制备方法和含有它们的药物组合物。 这些化合物对血管加压素和催产素受体具有亲和力。
• Dérivés de 1-benzyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, et compositions pharmaceutiques les contenant
  申请人：SANOFI

  公开号：EP0694536A1

  公开（公告）日：1996-01-31

  La présente invention concerne des dérivés de 1-benzyl-1,3-dihydro-2H-benzimidazol-2-one, de formule : et leurs sels éventuels, leur procédé de préparation ainsi que les compositions pharmaceutiques en contenant. Ces composés ont une affinité pour les récepteurs de la vasopressine et/ou de l'ocytocine.

  本发明涉及式.1-苄基-1,3-二氢-2H-苯并咪唑-2-酮衍生物： 及其任何盐类、其制备方法和含有它们的药物组合物。 这些化合物对血管加压素和/或催产素受体具有亲和力。
• Computational Strategies in Discovering Novel Non-nucleoside Inhibitors of HIV-1 RT
  作者：Maria Letizia Barreca、Angela Rao、Laura De Luca、Maria Zappalà、Anna-Maria Monforte、Giovanni Maga、Christophe Pannecouque、Jan Balzarini、Erik De Clercq、Alba Chimirri、Pietro Monforte

  DOI：10.1021/jm049279a

  日期：2005.5.1

  A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.
• US5585394A
  申请人：——

  公开号：US5585394A

  公开（公告）日：1996-12-17