2-chloro-5-(1-methyl-1H-imidazol-5-yl)pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-chloro-5-(1-methyl-1H-imidazol-5-yl)pyridine
• 英文别名: 2-chloro-5-(3-methyl-3H-imidazol-4-yl)-pyridine；2-chloro-5-(3-methylimidazol-4-yl)pyridine
• 化学式: C₉H₈ClN₃
• 分子量: 193.636
• InChiKey: ZVGGKATULXUPCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-3-(2,3-dihydrobenzofuran-5-yl)-9H-pyrrolo-[3,4-b]quinolin-9-one, hydrochloride salt 、 2-chloro-5-(1-methyl-1H-imidazol-5-yl)pyridine 在 palladium diacetate 、 sodium t-butanolate 、 2-(二环己基膦基)联苯 作用下， 以 1,4-二氧六环 为溶剂， 以12%的产率得到3-(2,3-Dihydro-benzofuran-5-yl)-2-[5-(3-methyl-3H-imidazol-4-yl)-pyridin-2-yl]-1,2,3,4-tetrahydro-pyrrolo[3,4-b]quinolin-9-one
  参考文献：
  名称：

  Pyrroloquinolone PDE5 Inhibitors with Improved Pharmaceutical Profiles for Clinical Studies on Erectile Dysfunction

  摘要：

  We previously reported a series of potent and selective pyrimidinyl pyrroloquinolone PDE5 inhibitors such as 2a for potential use in male erectile dysfunction (MED) (Sui, Z.; Guan, J.; Macielag, M. J.; Jiang, W.; Zhang, S.; Qiu, Y.; Kraft, P., Bhattacharjee, S.; John, T. M.; Craig, E.; Haynes-Johnson, D.; Clancy, J. J. Med. Chem. 2002, 45, 4094-4096). Unfortunately, the low aqueous solubility and poor oral bioavailability rendered them undesirable development candidates. To address this issue, we designed a series of analogues using two approaches: increasing the overall basicity and reducing molecular weight of the lead. Through earlier SAR studies, we discovered that the PDE5 potency of the pyrroloquinolones is insensitive to substitution on the pyrrole nitrogen. Basic functional groups such as pyridines and benzimidazoles were appended via the aromatic ring connected to the pyrrole nitrogen. Several truncated analogues were also designed and synthesized to improve oral absorption. These modifications allowed us to identify analogues with good oral bioavailability in rats, dogs, and monkeys while the high potency against PDE5 and desirable selectivity versus other PDE isozymes were maintained. Compounds R-11e and R-111 were selected as development candidates for MED and other indications.

  DOI：

  10.1021/jm0401098
• 作为产物：
  描述：

  N-甲基咪唑 、 5-溴-2-氯吡啶 在 [Pd(IPr*IMe)^An(3-Cl-pyridinyl)Cl₂] 、 potassium carbonate 、 三甲基乙酸 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 以75%的产率得到2-chloro-5-(1-methyl-1H-imidazol-5-yl)pyridine
  参考文献：
  名称：

  非对称Pd-PEPPSI-NHC配合物在温和条件下催化杂芳烃的直接（杂）芳基化

  摘要：

  为了开发一种方便有效的方法来获得结构上引人入胜的有价值的官能化（杂）芳基，制备了两种不对称的Pd-PEPPSI型NHC配合物（PEPPSI，吡啶增强的前催化剂的制备，稳定和引发; NHC，N-杂环碳烯被设计和合成，以催化杂芳烃与（杂）芳基溴化物的直接芳基化。结果表明，与通常使用的C 2相比，这种“非对称”策略的利用导致更高的效率。对称的Pd-PEPPSI型NHC复合物。此外，即使在低至0.05 mol％的催化剂负载量和好氧条件下，具有各种官能团的各种杂芳族和（杂）芳基溴伙伴也都符合开发的方案。更重要的是，随着我们的研究，我们还发现，本协议可以方便地访问肌肉松弛药dantrolene和共轭共聚聚合物的克级合成方法。

  DOI：

  10.1021/acs.organomet.0c00494

文献信息

• Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors
  申请人：——

  公开号：US20020010183A1

  公开（公告）日：2002-01-24

  The invention relates to novel pyrrolopyridinone derivatives of the formula (I) or (II): 1 pharmaceutical compositions containing the compounds and their use for the treatment of sexual dysfunction.

  这项发明涉及公式(I)或(II)的新型吡咯吡啶酮衍生物： 1 含有这些化合物的药物组合物及其用于治疗性功能障碍的用途。
• Developing Bis(imino)acenaphthene-Supported <i>N</i>-Heterocyclic Carbene Palladium Precatalysts for Direct Arylation of Azoles
  作者：Li-Qun Hu、Rong-Li Deng、Yan-Fen Li、Cui-Jin Zeng、Dong-Sheng Shen、Feng-Shou Liu

  DOI：10.1021/acs.organomet.7b00784

  日期：2018.1.22

  On the basis of the strategy of developing highly efficient protocol for Pd-catalyzed cross-coupling reactions, a series of bulky bis(imino)acenaphthene (BIAN)-supported Pd-PEPPSI complexes were synthesized, characterized, and applied in direct arylation of azoles. The effect of backbone and N-moieties on NHCs was evaluated, and the reaction conditions were optimized. It was found that the bulky Pd-PEPPSI complexes could be successfully employed in cross-coupling of (hetero)aryl bromides with azoles at a low palladium loading of 0.5-0.05 mol % under aerobic conditions, demonstrating the ease of manipulation without glovebox and handling of solvents.
• SUBSTITUTED PYRROLOPYRIDINONE DERIVATIVES USEFUL AS PHOSPHODIESTERASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1296981A2

  公开（公告）日：2003-04-02
• US6635638B2
  申请人：——

  公开号：US6635638B2

  公开（公告）日：2003-10-21
• US6818646B2
  申请人：——

  公开号：US6818646B2

  公开（公告）日：2004-11-16