tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate | 467423-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate；tert-butyl 4-(C-chloro-N-hydroxycarbonimidoyl)piperidine-1-carboxylate
• CAS: 467423-44-5
• 化学式: C₁₁H₁₉ClN₂O₃
• 分子量: 262.736
• InChiKey: WRCNVYRLKORNCB-UHFFFAOYSA-N

物化性质

• 沸点：
  376.6±52.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone
  参考文献：
  名称：

  Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator

  摘要：

  Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 7 2 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.

  DOI：

  10.1016/j.bmc.2019.115232
• 作为产物：
  描述：

  1-叔丁氧羰基哌啶-4-甲醛 在 盐酸 、 N-氯代丁二酰亚胺 、 盐酸羟胺 、 碳酸氢钠 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  一个基础促进氨基异恶唑的多谱图合成：药物发现和拟肽的有价值的组成部分†

  摘要：

  阐述了从可商购获得的氨基酸中实用的无重克合成含异恶唑结构单元的方法。关键反应是原位生成的腈氧化物与炔烃/烯胺的区域选择性[3 + 2]-环加成反应。所获得的结构单元用于制备生物活性化合物和拟肽。

  DOI：

  10.1039/c6ra02365g

文献信息

• [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2012169649A1

  公开（公告）日：2012-12-13

  The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]
• Solution-Phase Synthesis of a Diverse Library of Benzisoxazoles Utilizing the [3 + 2] Cycloaddition of in Situ-Generated Nitrile Oxides and Arynes
  作者：Anton V. Dubrovskiy、Prashi Jain、Feng Shi、Gerald H. Lushington、Conrad Santini、Patrick Porubsky、Richard C. Larock

  DOI：10.1021/co300159g

  日期：2013.4.8

  the [3 + 2] cycloaddition of nitrile oxides with arynes and further diversified by acylation/sulfonylation and palladium-catalyzed coupling processes. The eight key intermediate benzisoxazoles have been prepared by the reaction of o-(trimethylsilyl)aryl triflates and chlorooximes in the presence of CsF in good to excellent yields under mild reaction conditions. These building blocks have been used

  苯并异恶唑的文库是通过腈与芳烃的[3 + 2]环加成反应合成的，并通过酰化/磺酰化和钯催化的偶联过程进一步多样化。八种关键中间体苯并异恶唑是通过在CsF存在下，邻-（三甲基甲硅烷基）芳基三氟甲磺酸酯和氯肟在温和的反应条件下以良好或优异的收率反应制得的。这些构件已被用作各种3,5,6-三取代的苯并异恶唑的关键组分。
• Regioselective synthesis of isoxazole and 1,2,4-oxadiazole-derived phosphonates <i>via</i> [3 + 2] cycloaddition
  作者：Bohdan A. Chalyk、Alona S. Sosedko、Dmitriy M. Volochnyuk、Andrey A. Tolmachev、Konstantin S. Gavrilenko、Oleksandr S. Liashuk、Oleksandr O. Grygorenko

  DOI：10.1039/c8ob02257g

  日期：——

  results of the study on reactions of halogenoximes bearing (protected) functional groups or fluorinated substituents with various phosphorus-containing dipolarophiles are described. To control the regioselectivity of the reaction, vinylphosphonates bearing a leaving group (i.e. bromine or dialkylamino group) in the α or β position were used; 3,5- and 3,4-disubstituted isoxazoles were obtained in 47–80%

  描述了带有（保护的）官能团或氟化取代基的卤代肟与各种含磷的双亲性试剂反应的研究结果。为了控制反应的区域选择性，使用了在α或β位置带有离去基团（即溴或二烷基氨基）的乙烯基膦酸酯；3,5-和3,4-二取代异恶唑的产率分别为47-80％和63-75％。该反应对于母体膦酸乙烯基酯和氰基膦酸酯也是有效的。在这种情况下，分离出相应的异恶唑啉和1,2,4-恶二唑衍生的膦酸酯，产率分别为55-69％和34-73％。通过制备磷酸组氨酸的直接构象受限的类似物证明了所获得产物的实用性。
• Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
  作者：Chu-Biao Xue、John Wityak、Thais M. Sielecki、Donald J. Pinto、Douglas G. Batt、Gary A. Cain、Michael Sworin、Arlene L. Rockwell、John J. Roderick、Shuaige Wang、Michael J. Orwat、William E. Frietze、Lori L. Bostrom、Jie Liu、C. Anne Higley、F. Wayne Rankin、A. Ewa Tobin、George Emmett、George K. Lalka、Jean Y. Sze、Susan V. Di Meo、Shaker A. Mousa、Martin J. Thoolen、Adrienne L. Racanelli、Elizabeth A. Hausner、Thomas M. Reilly、William F. DeGrado、Ruth R. Wexler、Richard E. Olson

  DOI：10.1021/jm960799i

  日期：1997.6.1

  Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of

  使用异恶唑啉XR299（1a）作为设计高效，长效GPIIb / IIIa拮抗剂的起点，评估了将亲脂性取代基置于羧酸酯部分的α和β处的效果。在所研究的化合物中，发现氨基甲酸正丁酯24u在狗中表现出优异的效力和离体抗血小板作用的持续时间。用可替代的碱性基团取代苯并胺丁-4-基部分，消除异恶唑啉立体中心，并改变异恶唑啉环的方向，导致效力和/或作用时间降低。
• Synthesis of 5-(Fluoroalkyl)isoxazole Building Blocks by Regioselective Reactions of Functionalized Halogenoximes
  作者：Bohdan A. Chalyk、Kateryna V. Hrebeniuk、Yulia V. Fil、Konstantin S. Gavrilenko、Alexander B. Rozhenko、Bohdan V. Vashchenko、Oleksandr V. Borysov、Angelina V. Biitseva、Pavlo S. Lebed、Iulia Bakanovych、Yurii S. Moroz、Oleksandr O. Grygorenko

  DOI：10.1021/acs.joc.9b02264

  日期：2019.12.20

  halogenoximes and propargylic alcohol. An alternative approach based on nucleophilic substitution in 5-bromomethyl derivatives was found to be more convenient for the preparation of 5-fluoromethylisoxazoles. Reaction of isoxazole-5-carbaldehydes with the Ruppert-Prakash reagent was used for the preparation of (β,β,β-trifluoro-α-hydroxyethyl)isoxazoles. Utility of described approaches was shown by multigram preparation

  报道了从官能化的卤代肟开始合成5-氟烷基取代的异恶唑的综合研究。开发了无罐的CF3取代烯烃和带有酯，溴，氯甲基和受保护氨基的卤代肟的无金属[3 + 2]环加成反应，用于制备5-三氟甲基异恶唑。以区域选择性的方式以高达130g的规模以良好或优异的产率获得了目标3，5-二取代的衍生物。通过相应的5-羟甲基或5-甲酰基衍生物的后期脱氧氟化分别合成5-氟甲基-异氟唑和5-二氟甲基异恶唑，然后通过无金属环合肟和炔丙醇来制备5-氟甲基异恶唑。发现在5-溴甲基衍生物中基于亲核取代的替代方法对于制备5-氟甲基异恶唑更方便。将异恶唑-5-甲醛与Ruppert-Prakash试剂的反应用于制备（β，β，β-三氟-α-羟乙基）异恶唑。通过多链制备侧链官能化的单，二和三氟甲基异恶唑，例如，ABT-418和ESI-09的氟化类似物，表明了所描述方法的实用性。