5,6-二氢-4H-吡咯并[1,2-B]吡唑-3-甲醛 | 1260667-91-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡唑类
• 中文名称: 5,6-二氢-4H-吡咯并[1,2-B]吡唑-3-甲醛
• 英文名称: 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carbaldehyde
• CAS: 1260667-91-1
• 化学式: C₇H₈N₂O
• 分子量: 136.153
• InChiKey: LATQYZZGNADRLH-UHFFFAOYSA-N

物化性质

• 沸点：
  300.2±30.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H312,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  5,6-二氢-4H-吡咯并[1,2-B]吡唑-3-甲醛 在 盐酸羟胺 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carbaldehyde oxime
  参考文献：
  名称：

  Synthesis of (5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-methanamine

  摘要：

  This short paper reports the development of a new method for the synthesis of (5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)methanamine. Pyrazole was initially protected with an N-SEM protective group, followed by alkylation at C-5 position with 1-bromo-3-chloropropane. Following SEM deprotection, the intramolecular ring was closed and then a bromine atom (Br) was introduced with N-bromosuccinimide (NBS) by electrophilic aromatic substitution (SEAr), forming 3-bromo-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole. The Br group was subsequently converted into aldehyde group, then into oxime. The final step of hydrogenation resulted in the desired product. The overall yield through the 8-step reaction process was found to be 29.4%. The intermediates and final product were identified by HPLC-MS and H-1 NMR. This development provides a novel synthetic route to the formation of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole skeleton.

  DOI：

  10.3987/com-17-13772
• 作为产物：
  描述：

  5-(3-chloropropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.5h， 生成 5,6-二氢-4H-吡咯并[1,2-B]吡唑-3-甲醛
  参考文献：
  名称：

  Synthesis of (5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-methanamine

  摘要：

  This short paper reports the development of a new method for the synthesis of (5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)methanamine. Pyrazole was initially protected with an N-SEM protective group, followed by alkylation at C-5 position with 1-bromo-3-chloropropane. Following SEM deprotection, the intramolecular ring was closed and then a bromine atom (Br) was introduced with N-bromosuccinimide (NBS) by electrophilic aromatic substitution (SEAr), forming 3-bromo-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole. The Br group was subsequently converted into aldehyde group, then into oxime. The final step of hydrogenation resulted in the desired product. The overall yield through the 8-step reaction process was found to be 29.4%. The intermediates and final product were identified by HPLC-MS and H-1 NMR. This development provides a novel synthetic route to the formation of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole skeleton.

  DOI：

  10.3987/com-17-13772

文献信息

• Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain
  作者：R. Aldrin Denny、Andrew C. Flick、Jotham Coe、Jonathan Langille、Arindrajit Basak、Shenping Liu、Ingrid Stock、Parag Sahasrabudhe、Paul Bonin、Duncan A. Hay、Paul E. Brennan、Mathew Pletcher、Lyn H. Jones、Eugene L. Piatnitski Chekler

  DOI：10.1021/acs.jmedchem.6b01839

  日期：2017.7.13

  biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An

  临床前靶标验证需要化学探针，以探询新的生物学靶标和途径。需要CREB结合蛋白（CREBBP）/ EP300溴结构域的选择性抑制剂，以促进阐明与这些重要表观遗传学靶标相关的生物学。特别关注物化性质的药物化学优化为化学探针提供了理想的效价，选择性和渗透性属性。优化过程的重要特征是成功应用基于合理结构的药物设计来解决溴结构域选择性问题（尤其是针对与结构相关的BRD4蛋白）。
• C−C Coupling through Nitrogen Deletion: Application to Library Synthesis
  作者：Serhii Holovach、Kostiantyn P. Melnykov、Illia Poroshyn、Rustam T. Iminov、Dmytro Dudenko、Ivan Kondratov、Mark Levin、Oleksandr O. Grygorenko

  DOI：10.1002/chem.202203470

  日期：2023.1.18

  A reductive amination-“nitrogen deletion” reaction sequence employing (hetero)aromatic aldehydes and (het)arylmethyl amines as the building blocks, and anomeric amide as the reagent was implemented for the parallel synthesis of compound libraries. The method gave access to a chemical space of over half a million compounds relevant to early drug-discovery initiatives.

  采用（杂）芳香醛和（杂）芳基甲基胺作为结构单元，异头酰胺作为试剂的还原胺化-“氮缺失”反应序列用于化合物库的平行合成。该方法可以访问与早期药物发现计划相关的超过 50 万种化合物的化学空间。
• [EN] ISOQUINOLINONE AND QUINAZOLINONE COMPOUNDS, AND COMPOSITION AND USE THEREOF<br/>[FR] COMPOSÉS ISOQUINOLINONE ET QUINAZOLINONE, ET COMPOSITION ET UTILISATION DE CEUX-CI<br/>[ZH] 异喹啉酮类及喹唑啉酮类化合物及其组合物和用途
  申请人：[en]ZHONGSHAN INNOVATION BIOPHARMACEUTICAL CO., LTD.;[zh]中山医诺维申新药研发有限公司

  公开号：WO2023051495A1

  公开（公告）日：2023-04-06

  涉及式(I)或(II)所示的异喹啉酮类及喹唑啉酮类化合物，包含所述化合物的药物组合物以及使用所述化合物及其药物组合物在制备预防、处理、治疗、和/或减轻PI3-激酶介导的疾病、病症、和/或病况，或抑制PI3-激酶活性的药物中的用途。所述化合物对目标激酶显示出优异的抑制活性和激酶选择性，具有良好的药代动力学性质，生物利用度更高。
• [EN] BENZOTHIAZOLE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE BENZOTHIAZOLE ET LEURS UTILISATIONS
  申请人：YUMANITY THERAPEUTICS INC

  公开号：WO2021247921A8

  公开（公告）日：2022-01-27