2-phenethyl-1,2-dihydro-3H-indazol-3-one | 120273-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 2-phenethyl-1,2-dihydro-3H-indazol-3-one
• 英文别名: 2-Phenethyl-1,2-dihydro-indazol-3-one；2-(2-phenylethyl)-1H-indazol-3-one
• CAS: 120273-85-0
• 化学式: C₁₅H₁₄N₂O
• 分子量: 238.289
• InChiKey: HCKFBGZZOSOLAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  furfural tosylhydrazone 、 2-phenethyl-1,2-dihydro-3H-indazol-3-one 在 palladium diacetate 、 caesium carbonate 作用下， 以 甲苯 为溶剂， 以77%的产率得到2-(2-furyl)-3-(2-phenylethyl)-2,3-dihydroquinazolin-4(1H)-one
  参考文献：
  名称：

  通过 Pd 催化卡宾插入 N-N 键将吲唑酮串联转化为喹唑啉酮

  摘要：

  1-aryl- 和 2-aryl-1,2-dihydro-3 H -indazol-3-ones 向 1,2-di(hetero)aryl- 和 2,3-di(hetero)aryl- 的意外加速转化2,3-dihydroquinazolin-4(1 H )-ones 分别通过与醛类N-甲苯磺酰腙反应高效地获得。该方案通过一个级联过程进行，包括通过N-甲苯磺酰腙的分解产生碱介导的 Pd-类胡萝卜素、吲唑酮对 Pd-类胡萝卜素复合物的亲核攻击，以及通过 N-N 键裂解进行的分子内环扩展。该策略的实用性在生物活性 NPS 53574（一种钙受体拮抗剂）的合成中得到了证明。

  DOI：

  10.1021/acs.joc.2c02437
• 作为产物：
  描述：

  N-phenethyl-2-nitrobenzamide 在 sodium hydroxide 、 锌 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以42%的产率得到2-phenethyl-1,2-dihydro-3H-indazol-3-one
  参考文献：
  名称：

  Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity

  摘要：

  Since the hypothetical mechanisms of hydroperoxydation of arachidonic acid by, respectively, 5-lipoxygenase (5-LPO) and cyclooxygenase (CO) involve a redox cycle, a compound which reduces 5-LPO and CO to their inactive state would give a nonselective inhibitor of both enzymes. Structural modifications of such a compound could be expected to give improved potency and selectivity for 5-LPO and oral activity. Such an approach has led to the discovery of 1,2-dihydroindazol-3-ones which are potent 5-LPO inhibitors with various degrees of selectivity. Structure-activity relationship studies indicated that while N-1,N-2-unsubstituted and N-1-substituted derivatives are orally inactive, N-2-alkyl derivatives are orally active and inhibit both 5-LPO and CO. In contrast, N-2-benzyl derivatives are selective for 5-LPO but possess only weak oral activity. Further structural modifications have identified ICI 207968 [1,2-dihydro-2-(3-pyridylmethyl)-3H-indazol-3-one, 21a] which combines potent oral activity and high selectivity. Methemoglobin (MHb) induction by 21a in dog blood precluded its development for clinical use. Attempts at dissociating 5-LPO inhibitory properties and MHb formation showed that MHb formation in vitro seemed to be related to the redox potential of the compounds whereas 5-LPO inhibition was not. This study led to a series of 4-(N-n-pentylcarbamoyl)indazolinones which maintained in vitro 5-LPO potency but did not induce MHb.

  DOI：

  10.1021/jm00107a023

文献信息

• Photocatalyst‐free Synthesis of Indazolones under CO ₂ Atmosphere
  作者：Tianbao Yang、Huiai Lu、Renhua Qiu、Ling Hong、Shuang‐Feng Yin、Nobuaki Kambe

  DOI：10.1002/asia.201900306

  日期：2019.5.2

  A convenient photocatalyst‐free method for the synthesis of redox‐active 1,2‐dihydro‐3H‐indazol‐3‐one derivatives from (2‐nitroaryl)methanol and amines was developed. The reaction proceeded efficiently at room temperature by irradiation of UV light under CO2 atmosphere (1.0 atm, flow) without any photocatalysts or additives. This mild, operationally simple method shows wide functional tolerance. The

  开发了一种简便的无光催化剂方法，可从（2-硝基芳基）甲醇和胺类合成氧化还原活性的1,2-二氢-3 H-吲唑-3-酮衍生物。在室温下，通过在无任何光催化剂或添加剂的情况下，通过在CO 2气氛（1.0 atm，流量）下照射紫外线，使反应有效地进行。这种温和，操作简单的方法显示出广泛的功能公差。由CO 2和胺原位形成的氨基甲酸酯被认为是该反应的关键。已发现通过本方法合成的某些化合物具有较高的抗癌活性，可降低癌细胞系HeLa，MCF-7和U87的活力。
• 一种二氧化碳促进和无光催化剂光诱导合成吲唑啉酮类化合物制备方法
  申请人：湖南大学

  公开号：CN109734666B

  公开（公告）日：2023-03-28

  本发明以喹啉2‑硝基苯甲醇类化合物、胺类衍生物为原料，以廉价、易得的普通灯泡作为反应的光源，以二氧化碳为促进剂，以常用的有机溶剂作反应溶剂，反应在一定温度下反应一定时间，高产率、高选择性地得到吲唑啉酮类化合物，并且在克级放大反应中得到很高的产率。
• Photochemical Preparation of 1,2-Dihydro-3<i>H</i>-indazol-3-ones in Aqueous Solvent at Room Temperature
  作者：Jie S. Zhu、Niklas Kraemer、Clarabella J. Li、Makhluf J. Haddadin、Mark J. Kurth

  DOI：10.1021/acs.joc.8b02356

  日期：2018.12.21

  involve its isolation via chromatography and/or formation under harsh conditions. Herein, this intermediate was photochemically generated in situ from o-nitrobenzyl alcohols in a mild, efficient manner for the construction of 1,2-dihydro-3 H-indazol-3-ones using an aqueous solvent at room temperature. This convenient reaction offers several advantages over reported methods. The commercially available photoreactor

  邻硝基苯甲醛是一种反应性中间体，可用于合成氮杂环。以前使用邻亚硝基苯甲醛的策略涉及通过色谱分离和/或在苛刻条件下形成。在此，该中间体以温和，有效的方式从邻硝基苄基醇原位光化学生成，用于在室温下使用水性溶剂构建1,2-二氢-3 H-吲唑-3-酮。与报道的方法相比，这种方便的反应具有多个优点。市售的光反应器使用3×18 W灯泡，可在365 nm以上发出宽广的发射光。
• A B₂(OH)₄-Mediated Synthesis of 2-Substituted Indazolone and Its Application in a DNA-Encoded Library
  作者：Yapeng Bao、Zongfa Deng、Jing Feng、Weiwei Zhu、Jin Li、Jinqiao Wan、Guansai Liu

  DOI：10.1021/acs.orglett.0c02032

  日期：2020.8.21

  Indazolone cores are among the most common structural components in medicinal chemistry and can be found in many biologically active molecules. In this report, a mild and efficient approach to 2-substituted indazolones via B-2(OH)(4)-mediated reductive N-N bond formation is developed. This strategy features mild conditions, no request for a metal catalyst, and a wide scope for both aliphatic and aromatic amines. Meanwhile, this method was further successfully applied on DNA to construct indazolone cores for a DNA-encoded library. This will enable the production of a very attractive indazolone-cored library from simple amines and scaffolds, which will provide considerable diversity.
• N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2-Substituted Indazolones with Mechanistic Insights
  作者：Jie S. Zhu、Niklas Kraemer、Marina E. Shatskikh、Clarabella J. Li、Jung-Ho Son、Makhluf J. Haddadin、Dean J. Tantillo、Mark J. Kurth

  DOI：10.1021/acs.orglett.8b01655

  日期：2018.8.17

  A concise, one-step route to indazolones from primary alkyl amines and o-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated in situ o-nitrobenzyl alcohol -> o-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2H-indazole synthesis, its reactivity was modulated for indazolone formation.