Ethyl 6-chloro-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate | 161468-51-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: Ethyl 6-chloro-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate
• 英文别名: ethyl 6-chloro-2-oxo-2,3-dihydrobenzimidazole-1-carboxylate；ethyl 6-chloro-2-oxo-3H-benzimidazole-1-carboxylate
• CAS: 161468-51-5
• 化学式: C₁₀H₉ClN₂O₃
• 分子量: 240.646
• InChiKey: OLHTYVFWKCIBSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 6-chloro-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 1-benzyl-5-chloro-1H-benzo[d]imidazol-2(3H)-one
  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
• 作为产物：
  描述：

  2-羟基苯并咪唑 在 磺酰氯 、 potassium carbonate 作用下， 以 溶剂黄146 、 乙腈 为溶剂， 反应 1.5h， 生成 Ethyl 6-chloro-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate
  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

• SUBSTITUTED BENZIMIDAZOLONE DERIVATIVES, MEDICAMENTS COMPRISING THEM AND THEIR USE
  申请人：Arndt Torsten

  公开号：US20120172335A1

  公开（公告）日：2012-07-05

  The present invention relates to novel benzimidazolone derivatives of the general formula (I) in which the substituents R 1 , R 2 , R 3 , A 1 , A 2 , and B are as defined in claim 1 , medicaments comprising these, and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent diseases.

  本发明涉及一种新型苯并咪唑酮衍生物，其通式为（I），其中取代基R1、R2、R3、A1、A2和B如权利要求书所定义，包括这些衍生物的药物以及它们在抗利尿激素依赖性疾病的预防和/或治疗中的应用。
• Substituted benzimidazolone derivatives, medicaments comprising them and their use
  申请人：Abbott GmbH & Co. HG

  公开号：US08119676B2

  公开（公告）日：2012-02-21

  The present invention relates to novel benzimidazolone derivatives of the general formula (I) in which the substituents R1, R2, R3, A1, A2, and B are as defined in claim 1, medicaments comprising these, and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent diseases.

  本发明涉及一种新型苯并咪唑酮衍生物，其一般式为(I)，其中取代基R1、R2、R3、A1、A2和B的定义如权利要求书1所述，包括这些衍生物的药物，以及用于预防和/或治疗利尿激素依赖性疾病的使用。
• WO2008/25736
  申请人：——

  公开号：——

  公开（公告）日：——
• US8119676B2
  申请人：——

  公开号：US8119676B2

  公开（公告）日：2012-02-21
• US8791148B2
  申请人：——

  公开号：US8791148B2

  公开（公告）日：2014-07-29