(3-methoxypropyl)zinc(II) bromide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3-methoxypropyl)zinc(II) bromide
• 化学式: C₄H₉BrOZn
• 分子量: 218.409
• InChiKey: AZYFSOHVJNNHHX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.83
• 重原子数：
  7.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (3-methoxypropyl)zinc(II) bromide 、 1-(5-bromo-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea 在 2-双环己基膦-2',6'-二甲氧基联苯 、 palladium diacetate 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 1-(3-((2-ethylpyridin-3-yl)oxy)-5-(3-methoxypropyl)pyridin-2-yl)-3-methylurea
  参考文献：
  名称：

  C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators

  摘要：

  Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.

  DOI：

  10.1021/ml500341w
• 作为产物：
  描述：

  1-溴-3-甲氧基丙烷 、 zinc(II) chloride 在 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 生成 (3-methoxypropyl)zinc(II) bromide
  参考文献：
  名称：

  流动中有机锌试剂的产生和交叉偶联

  摘要：

  报道了一种通用的流动合成方法，用于原位形成有机锌试剂，然后与芳基卤化物和活化的羧酸进行交叉偶联。有机锌试剂的形成是通过在流动条件下将有机卤化物在ZnCl 2和LiCl的存在下泵送通过活化的Mg填充柱来实现的。该方法可有效地原位形成芳基，伯，仲和叔烷基有机锌试剂，随后将其在下游进行Negishi或脱羧Negishi交叉偶联反应的伸缩。所描述的方法提供了使用有机锌试剂获得各种C–C键的方法，这些试剂否则在商业上是不可用的，或者在传统的间歇反应条件下难以制备。

  DOI：

  10.1021/acs.orglett.8b03156

文献信息

• [EN] C(SP3)-C(SP2) CROSS-COUPLING REACTION OF ORGANOZINC REAGENTS AND HETEROCYCLIC (PSEUDO)HALIDES<br/>[FR] RÉACTION DE COUPLAGE CROISÉ C(SP3)-C(SP2) DE RÉACTIFS D'ORGANOZINC ET DE (PSEUDO)HALOGÉNURES HÉTÉROCYCLIQUES
  申请人：UNIV HONG KONG SCI & TECH

  公开号：WO2018019291A1

  公开（公告）日：2018-02-01

  Provided is a method of synthesizing a C(sp3)-C(sp2) cross-coupled compound comprising reacting a C(sp3) coupling partner with a C(sp2) coupling partner, a catalyst, and a solvent; wherein the C(sp3) coupling partner comprises an organic zinc reagent; and wherein the C(sp2) coupling partner comprises a heterocyclic halide or a heterocyclic pseudo halide. The method further comprises synthesis of the organic zinc reagent, wherein the synthesis comprises reacting a zinc powder with an acid, filtering, washing, and drying to obtain an activated zinc powder; and reacting the activated zinc powder with a metal iodide catalyst and a second solvent and heating for a predetermined time to obtain the organic zinc reagent.

  提供了一种合成C(sp3)-C(sp2)交叉偶联化合物的方法，包括将一个C(sp3)偶联配体与一个C(sp2)偶联配体、催化剂和溶剂反应；其中C(sp3)偶联配体包括有机锌试剂；而C(sp2)偶联配体包括杂环卤化物或杂环假卤化物。该方法进一步包括合成有机锌试剂，其中合成包括将锌粉与酸反应，过滤，洗涤和干燥以获得活化锌粉；并将活化锌粉与金属碘催化剂和第二溶剂反应并加热一定时间以获得有机锌试剂。
• Nickel‐Catalyzed Regioselective Intermolecular Dialkylation of Alkenylarenes: Generation of Two Vicinal C(sp³)−C(sp³) Bonds Across Alkenes**
  作者：Daniel M. Lux、Vivek Aryal、Doleshwar Niroula、Ramesh Giri

  DOI：10.1002/anie.202305522

  日期：2023.8.7

  A nickel-catalyzed dialkylation reaction of alkenylarenes with α-bromocarbonyls and alkylzinc reagents is reported wherein two alkyl-alkyl bonds are generated in one step.

  报道了一种镍催化的烯基芳烃与α-溴羰基和烷基锌试剂的二烷基化反应，其中一步生成两个烷基-烷基键。
• Generation and Cross-Coupling of Organozinc Reagents in Flow
  作者：Ananda Herath、Valentina Molteni、Shifeng Pan、Jon Loren

  DOI：10.1021/acs.orglett.8b03156

  日期：2018.12.7

  formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl2 and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents

  报道了一种通用的流动合成方法，用于原位形成有机锌试剂，然后与芳基卤化物和活化的羧酸进行交叉偶联。有机锌试剂的形成是通过在流动条件下将有机卤化物在ZnCl 2和LiCl的存在下泵送通过活化的Mg填充柱来实现的。该方法可有效地原位形成芳基，伯，仲和叔烷基有机锌试剂，随后将其在下游进行Negishi或脱羧Negishi交叉偶联反应的伸缩。所描述的方法提供了使用有机锌试剂获得各种C–C键的方法，这些试剂否则在商业上是不可用的，或者在传统的间歇反应条件下难以制备。
• C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators
  作者：Xiaohui Du、Ronald J. Hinklin、Yumei Xiong、Paul Dransfield、Jaehyeon Park、Todd J. Kohn、Vatee Pattaropong、SuJen Lai、Zice Fu、Xianyun Jiao、David Chow、Lixia Jin、Jasmine Davda、Murielle M. Veniant、Deborah A. Anderson、Brian R. Baer、Josef R. Bencsik、Steven A. Boyd、Mark Joseph Chicarelli、Peter J. Mohr、Bin Wang、Kevin R. Condroski、Walter E. DeWolf、Marion Conn、Thanhvien Tran、Jerry Yang、Thomas D. Aicher、Julio C. Medina、Peter Coward、Jonathan B. Houze

  DOI：10.1021/ml500341w

  日期：2014.12.11

  Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.