3-(环己基甲基)-1H-苯并咪唑-2-酮 | 161469-11-0

• 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: 3-(环己基甲基)-1H-苯并咪唑-2-酮
• 英文名称: 1,3-Dihydro-1-(cyclohexylmethyl)-2H-benzimidazol-2-one
• 英文别名: 1-(cyclohexylmethyl)-1,3-dihydro-2H-benzimidazol-2-one；2H-Benzimidazol-2-one, 1-(cyclohexylmethyl)-1,3-dihydro-；3-(cyclohexylmethyl)-1H-benzimidazol-2-one
• CAS: 161469-11-0
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: WWRXQLHBUBAHSK-UHFFFAOYSA-N

物化性质

• 密度：
  1.139±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 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 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.5h， 生成 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

• [EN] IL4I1 INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS D'IL4I1 ET PROCÉDÉS D'UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2021226003A1

  公开（公告）日：2021-11-11

  Described herein are compounds of Formula I or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as IL4I1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for IL4I1-related diseases.

  本文描述了化合物I的结构或其药用盐。化合物I作为IL4I1抑制剂，可用于预防、治疗或作为IL4I1相关疾病的治疗剂。
• Benzimidazolone derivatives displaying affinity at the serotonin and dopamine receptors
  申请人：——

  公开号：US20020103208A1

  公开（公告）日：2002-08-01

  Compound of formula (I) 1 wherein: R 1 is hydrogen or C 1 -C 6 -alkyl optionally substituted by C 3 -C 6 -cycloylalkyl; R 2 and R 3 together with the nitrogen form a saturated or unsaturated 5- or 6-membered heterocyclic ring optionally containing nitrogen or oxygen as an additional heteroatom, wherein the heterocyclic ring thereof is substituted by a group selected from phenyl, benzyl, and diphenylmethyl, each optionally mono- or di-substituted by one or two groups selected from CF 3 , C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, phenyl, benzyl, halogen, and OH, or R 2 and R 3 together with the nitrogen form a saturated or unsaturated 5- or 6-membered heterocyclic ring optionally containing nitrogen or oxygen as an additional heteroatom, the heterocyclic ring thereof linked via a single bond, a methylene-bridge, or spiro-connected to another saturated or unsaturated heterocyclic group containing one or two heteroatoms selected from oxygen and nitrogen, the heterocyclic group being optionally mono- or di-substituted by a group selected from CF 3 , C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, phenyl, benzyl, halogen, =O, and OH, or R 2 and R 3 together with the nitrogen form a saturated or unsaturated bi- or tricyclic heterocyclic ring system optionally containing nitrogen or oxygen as an additional heteroatom, the heterocyclic ring system is optionally substituted by a group selected from CF 3 , C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, phenyl, benzyl, halogen, =O, and OH; and A is C 2 -C 6 -alkenylene, their pharmaceutically acceptable salts, their preparation, and their use for therapeutic purposes.

  化合物的公式(I)1，其中： R1是氢或C1-C6-烷基，该烷基可选择性地被C3-C6-环烷基取代； R2和R3与氮一起形成饱和或不饱和的5-或6-成员杂环，该杂环可选择性地含有氮或氧作为附加杂原子，其中所述杂环被苯基，苄基和二苯甲基中的一种取代，每种取代可选择性地单取代或双取代于一或两个CF3，C1-C4-烷基，C1-C4-烷氧基，苯基，苄基，卤素和OH中的一种或两种；或者R2和R3与氮一起形成饱和或不饱和的5-或6-成员杂环，该杂环可选择性地含有氮或氧作为附加杂原子，其中所述杂环通过单键，亚甲基桥或螺环连接到另一个饱和或不饱和的含有一个或两个氧和氮杂原子的杂环基团，所述杂环基团可选择性地单取代或双取代于一或两个CF3，C1-C4-烷基，C1-C4-烷氧基，苯基，苄基，卤素，=O和OH中的一种或两种；或者R2和R3与氮一起形成饱和或不饱和的双环或三环杂环系统，该杂环系统可选择性地含有氮或氧作为附加杂原子，该杂环系统可选择性地被CF3，C1-C4-烷基，C1-C4-烷氧基，苯基，苄基，卤素，=O和OH中的一种或两种取代；以及 A是C2-C6-烯基，它们的药学上可接受的盐，它们的制备以及它们用于治疗目的的用途。
• US6586435B2
  申请人：——

  公开号：US6586435B2

  公开（公告）日：2003-07-01
• Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives
  作者：Nicholas A. Meanwell、Sing Yuen Sit、Jinnian Gao、Henry S. Wong、Qi Gao、Denis R. St. Laurent、Neelakantan Balasubramanian

  DOI：10.1021/jo00111a014

  日期：1995.3

  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.