2-bromo-5-[(tetrahydro-2H-pyran-2-yloxy)-methyl]pyridine | 288372-63-4

• 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-bromo-5-[(tetrahydro-2H-pyran-2-yloxy)-methyl]pyridine
• 英文别名: 2-[(2-Bromopyridin-5-yl)methoxy]tetrahydro-2H-pyran；2-bromo-5-(oxan-2-yloxymethyl)pyridine
• CAS: 288372-63-4
• 化学式: C₁₁H₁₄BrNO₂
• 分子量: 272.142
• InChiKey: HMUPAFGLFJISNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-5-[(tetrahydro-2H-pyran-2-yloxy)-methyl]pyridine 在 氢溴酸 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 27.0h， 生成
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat.

  DOI：

  10.1021/jm501608q
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 、 6-溴-3-羟甲基吡啶 在 对甲苯磺酸 作用下， 以 氯仿 为溶剂， 以81%的产率得到2-bromo-5-[(tetrahydro-2H-pyran-2-yloxy)-methyl]pyridine
  参考文献：
  名称：

  蛋白质-无机阵列构建：构建模块的设计和合成

  摘要：

  在这里，我们描述了用于无机蛋白质骨架定向构建的第一系列双功能配体的设计和合成。合成的配体由结合到环氧琥珀酰肽上的金属离子结合部分（基于吡啶）组成，已知该肽通过活性位点的半胱氨酸与活性半胱氨酸蛋白酶共价结合。我们探索并优化了双官能化金属离子配体与含环氧琥珀酰的肽部分之间的两种不同的缀合化学：肽键形成（成功有限）和Cu I催化的点击化学（良好结果）。此外，合成的配体与Fe II和Ni II的络合对离子进行了研究：证实双功能配体的行为与母体吡啶相同。按照设计，尽管单击反应产生了两个三唑环，但肽部分不会干扰络合反应。ES‐MS与NMR和UV / Vis研究一起确定了结构，络合反应的化学计量，以及对化学敏感的含多肽的聚吡啶配体进行自组装的条件。这些结果确立了我们方法的多功能性，并为合成含有更多精心设计的聚吡啶配体以及针对不同酶家族的亲和标记物的双功能配体开辟了道路。因此，

  DOI：

  10.1002/chem.200902649

文献信息

• Organosilicon compounds and uses thereof
  申请人：Northwestern University

  公开号：US06416861B1

  公开（公告）日：2002-07-09

  A compound of the formula: and a resin-bound compound of the formula: and their use in combinatorial chemistry and in the synthesis of compounds comprising at least one aromatic moiety is described, where R1, R2, R3, R4, R5, R6, R7, L1, P, Ar1, and X are as herein defined.

  本文描述了一个公式的化合物：以及一个公式的树脂结合化合物：以及它们在组合化学和合成至少含有一个芳香基团的化合物中的应用，其中R1，R2，R3，R4，R5，R6，R7，L1，P，Ar1和X的定义如本文所述。
• US6416861B1
  申请人：——

  公开号：US6416861B1

  公开（公告）日：2002-07-09
• [EN] ORGANOSILICON COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSES D'ORGANOSILICIES ET LEURS UTILISATIONS
  申请人：UNIV NORTHWESTERN

  公开号：WO2000049022A2

  公开（公告）日：2000-08-24

  A compound of formula (I) and a resin-bound compound of formula (II): and their use in combinatorial chemistry and in the synthesis of compounds comprising at least one aromatic moiety is described, where R?1, R2, R3, R4, R5, R6, R7, L1, P, Ar1¿, and X are as herein defined.
• Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Brian D. Palmer、Hamish S. Sutherland、Adrian Blaser、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny、Andrew M. Thompson

  DOI：10.1021/jm501608q

  日期：2015.4.9

  Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat.
• Protein-Inorganic Array Construction: Design and Synthesis of the Building Blocks
  作者：Niculina D. Bogdan、Mihaela Matache、Veronika M. Meier、Cristian Dobrotă、Ioana Dumitru、Gheorghe D. Roiban、Daniel P. Funeriu

  DOI：10.1002/chem.200902649

  日期：2010.2.15

  Herein we describe the design and synthesis of the first series of di‐functional ligands for the directed construction of inorganic‐protein frameworks. The synthesized ligands are composed of a metal‐ion binding moiety (terpyridine‐based) conjugated to an epoxysuccinyl peptide, known to covalently bind active cysteine proteases through the active‐site cysteine. We explore and optimize two different

  在这里，我们描述了用于无机蛋白质骨架定向构建的第一系列双功能配体的设计和合成。合成的配体由结合到环氧琥珀酰肽上的金属离子结合部分（基于吡啶）组成，已知该肽通过活性位点的半胱氨酸与活性半胱氨酸蛋白酶共价结合。我们探索并优化了双官能化金属离子配体与含环氧琥珀酰的肽部分之间的两种不同的缀合化学：肽键形成（成功有限）和Cu I催化的点击化学（良好结果）。此外，合成的配体与Fe II和Ni II的络合对离子进行了研究：证实双功能配体的行为与母体吡啶相同。按照设计，尽管单击反应产生了两个三唑环，但肽部分不会干扰络合反应。ES‐MS与NMR和UV / Vis研究一起确定了结构，络合反应的化学计量，以及对化学敏感的含多肽的聚吡啶配体进行自组装的条件。这些结果确立了我们方法的多功能性，并为合成含有更多精心设计的聚吡啶配体以及针对不同酶家族的亲和标记物的双功能配体开辟了道路。因此，