3-(4-溴-1H-吡唑-1-基)氮杂环丁烷-1-羧酸叔丁酯 | 877399-34-3

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 中文名称: 3-(4-溴-1H-吡唑-1-基)氮杂环丁烷-1-羧酸叔丁酯
• 英文名称: tert-butyl 3-(4-bromo-1H-pyrazol-1-yl)azetidine-1-carboxylate
• 英文别名: tert-butyl 3-(4-bromopyrazol-1-yl)azetidine-1-carboxylate
• CAS: 877399-34-3
• 化学式: C₁₁H₁₆BrN₃O₂
• mdl: MFCD17480368
• 分子量: 302.171
• InChiKey: DYBIXDJMIONIDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.636
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P301+P310
• 危险品运输编号：
  2811
• 危险性描述：
  H301

反应信息

• 作为反应物：
  描述：

  3-(4-溴-1H-吡唑-1-基)氮杂环丁烷-1-羧酸叔丁酯 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 potassium acetate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 5-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine
  参考文献：
  名称：

  Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)

  摘要：

  Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.

  DOI：

  10.1021/jm2007613
• 作为产物：
  描述：

  1-Boc-3-氮杂环丁酮 在 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-(4-溴-1H-吡唑-1-基)氮杂环丁烷-1-羧酸叔丁酯
  参考文献：
  名称：

  [EN] ARYLSULPHONAMIDE COMPOUNDS
  [FR] COMPOSÉS D'ARYLSULFONAMIDE

  摘要：

  This invention relates to compounds of formula (I) and salts, solvates, tautomers, N-oxides, stereoisomers, polymorphs and/or prodrugs thereof. Also disclosed is the use of the compounds of formula (I) to treat necroptosis and/or inhibit MLKL.

  公开号：

  WO2023115142A1

文献信息

• NITROGEN-CONTAINING HETEROCYCLIC COMPOUND OR SALT THEREOF
  申请人：FUJIFILM Corporation

  公开号：US20150322063A1

  公开（公告）日：2015-11-12

  A compound represented by Formula [1] (in the formula, Z 1 represents N, CH, or the like; X 1 represents NH or the like; R 1 represents a heteroaryl group or the like; each of R 2 , R 3 , and R 4 represents a hydrogen atom, a halogen atom, an alkoxy group, or the like; and R 5 represents a heteroaryl group or the like) or salt thereof.

  由式[1]表示的化合物（在该式中，Z表示N、CH或类似物；X表示NH或类似物；R表示杂环烷基或类似物；R2、R3和R4中的每一个表示氢原子、卤原子、烷氧基或类似物；R5表示杂环烷基或类似物）或其盐。
• NAPHTHYRIDINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282328A1

  公开（公告）日：2018-10-04

  Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

  萘啶化合物及其作为HPK1抑制剂的用途被描述。这些化合物在治疗HPK1依赖性疾病和增强免疫反应方面很有用。还描述了抑制HPK1的方法、治疗HPK1依赖性疾病的方法、增强免疫反应的方法以及制备萘啶化合物的方法。
• Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060046991A1

  公开（公告）日：2006-03-02

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了式1的对映纯化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• Hydrogen Bonding Phase-Transfer Catalysis with Ionic Reactants: Enantioselective Synthesis of γ-Fluoroamines
  作者：Giulia Roagna、David M. H. Ascough、Francesco Ibba、Anna Chiara Vicini、Alberto Fontana、Kirsten E. Christensen、Aldo Peschiulli、Daniel Oehlrich、Antonio Misale、Andrés A. Trabanco、Robert S. Paton、Gabriele Pupo、Véronique Gouverneur

  DOI：10.1021/jacs.0c05131

  日期：2020.8.19

  salts are used as phase-transfer catalysts for fluorination with alkali metal fluorides. We now demonstrate that these organic salts, specifically azetidinium triflates, are suitable substrates for enantioselective ring opening with CsF and a chiral bis-urea catalyst. This process, which highlights the ability of hydrogen bonding phase-transfer catalysts to couple two ionic reactants, affords enantioenriched

  铵盐用作碱金属氟化物氟化的相转移催化剂。我们现在证明这些有机盐，特别是氮杂环丁烷三氟甲磺酸盐，是用 CsF 和手性双脲催化剂对映选择性开环的合适底物。该过程突出了氢键相转移催化剂偶联两种离子反应物的能力，以高产率提供了对映体富集的 γ-氟胺。机理研究强调了催化剂在相转移中的作用，并且计算出的过渡态结构解释了对非手性氮杂环丁烷非对映异构体混合物观察到的对映收敛。亲电子试剂中的 N 取代基会影响反应性，但氮的构型对于对映选择性并不重要。
• [EN] 7-AZOLE SUBSTITUTED 2-AMINOQUINAZOLINE INHIBITORS OF HPK1<br/>[FR] INHIBITEURS, DU TYPE 2-AMINOQUINAZOLINE À SUBSTITUTION 7-AZOLE, DE HPK1
  申请人：MERCK SHARP & DOHME

  公开号：WO2022098807A1

  公开（公告）日：2022-05-12

  Compounds of the following formula (I); or the pharmaceutically acceptable salts thereof, are inhibitors of haematopoietic progenitor kinase 1 (HPK1) useful in the treatment of diseases or disorders associated with HPK1. Also disclosed herein are uses of these compounds in the potential treatment or prevention of an HPK1-associated disease or disorder. Also disclosed herein are compositions comprising one or more of the compounds. Further disclosed herein are uses of these compositions in the potential prevention or treatment of an HPK1-associated disease or disorder.

  以下化合物(I)的药物可接受的盐是血液造血祖细胞激酶1(HPK1)的抑制剂，有用于治疗与HPK1相关的疾病或疾病的作用。本文还披露了这些化合物在潜在的治疗或预防HPK1相关疾病或疾病中的用途。本文还披露了包含一个或多个化合物的组合物。此外，本文还披露了这些组合物在潜在的预防或治疗HPK1相关疾病或疾病中的用途。