2-氯-2-甲基丙烷-d9 | 918-20-7

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 烃类卤化物
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氯化物
• 中文名称: 2-氯-2-甲基丙烷-d9
• 中文别名: 叔丁基氯-D9
• 英文名称: tert-butyl chloride-d9
• 英文别名: tert-butyl-d9 chloride；d₉-tert-butyl chloride；(2H9)-tert-Butyl chloride；2-chloro-1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propane
• CAS: 918-20-7
• 化学式: C₄H₉Cl
• 分子量: 101.497
• InChiKey: NBRKLOOSMBRFMH-GQALSZNTSA-N

物化性质

• 熔点：
  -25 °C(lit.)
• 沸点：
  51-52 °C(lit.)
• 密度：
  0.933 g/mL at 25 °C
• 闪点：
  65 °F
• 溶解度：
  氯仿（可溶）、甲醇（微量）
• 稳定性/保质期：
  在常温常压下稳定。

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  5
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

安全信息

• 危险品标志：
  F
• 安全说明：
  S16,S29,S33,S7/9
• 危险类别码：
  R11
• WGK Germany：
  3
• 危险品运输编号：
  UN 1127 3
• 储存条件：
  储存条件：0-6℃，避免光线直射，存放在通风干燥的地方。

制备方法与用途

2-氯-2-甲基丙烷-d⁹是一种氘标记的2-氯-2-甲基丙烷[1]。

反应信息

• 作为反应物：
  描述：

  2-氯-2-甲基丙烷-d9 在 铂 magnesium 、 氘 作用下， 生成 2-甲基丙烷-d10
  参考文献：
  名称：

  Kinetic isotope effects for hydrogen abstraction from a series of cycloalkanes and branched alkanes by hydrogen atoms in the gaseous phase

  摘要：

  DOI：

  10.1021/ja00292a024
• 作为产物：
  描述：

  叔丁醇-D9 在 盐酸 作用下， 以 水 为溶剂， 生成 2-氯-2-甲基丙烷-d9
  参考文献：
  名称：

  Models for Nonheme Iron Intermediates:  Structural Basis for Tuning the Spin States of Fe(TPA) Complexes

  摘要：

  Our efforts to model the oxygen activation chemistry of nonheme iron enzymes have yielded transient intermediates with novel properties. These properties can be dramatically affected by the introduction of a 6-methyl substituent on the pendant pyridines of the tetradentate ligand TPA (TPA = tris(2-pyridylmethyl)amine). A series of Fe(TPA) complexes has thus been synthesized and characterized to provide the structural basis for these dramatic effects. The following complexes have been obtained: [Fe(L)(CH3CN)(2)](ClO4)(2) (1, L = TPA; 2, L = 6-MeTPA; 3, L = 6-Me(2)TPA; 4, L = 6-Me(3)TPA) and [Fe(L)(acac)](ClO4)(2) (5, L = TPA; 6, L = 5-Me(3)TPA; 7, L = 6-MeTPA). As indicated by H-1 NMR and/or EPR, 1, 5, and 6 wish no 6-methyl substituent are low spin, while complexes 2, 3, 4, and 7 with at least one 6-methyl substituent are all high spin, with higher redox potentials than their low-spin counterparts. The ligands with 6-methyl substituents thus favor a metal center with a larger ionic radius, i.e., Fe-II over Fe-III and high spin over low spin. Careful scrutiny of the crystal structures of 1, 4, 6, and 7 reveals that one hydrogen of the 6-methyl group is only 2.7 Angstrom away from the metal center in the high-spin complexes. Its presence thus prevents the pyridine nitrogen from forming an Fe-N bond shorter than 2.1 Angstrom as required for an iron center to adopt a low-spin configuration. This steric effect of the 6-methyl substituent serves as a simple but very useful ligand design tool to tune the electronic properties of the metastable alkylperoxoiron(III) species derived from the reactions of 1-4 with tert-butyl hydroperoxide. These intermediates serve as models for low-spin and high-spin peroxoiron(III) species in the reaction cycles of the antitumor drug bleomycin and lipoxygenase, respectively. Similar principles apply in the design of nonheme diiron(II) complexes that reversibly bind dioxygen and of high-valent bis(mu-oxo)diiron complexes that model the high-valent intermediates in the redox cycles of nonheme diiron enzymes such as methane monooxygenase and ribonucleotide reductase.

  DOI：

  10.1021/ja9638521
• 作为试剂：
  描述：

  二苯基乙炔 在 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 2-氯-2-甲基丙烷-d9 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以98%的产率得到C₁₄H₁₀⁽²⁾HCl
  参考文献：
  名称：

  通过穿梭催化铱催化氢氯化和氢溴化炔烃。

  摘要：

  本文描述了通过未活化炔烃的基于铱催化的转移氢卤化的穿梭催化来合成卤乙烯的两种不同方法。使用 4-氯丁烷-2-酮或叔丁基卤化物作为卤化氢的供体，可以在没有腐蚀性试剂（例如卤化氢或酰基氯）的情况下进行这种转化，从而大大提高了官能团耐受性和安全性。这些反应与最先进的反应相比。该方法可以制备含有酸敏感基团的烯基卤化合物，例如叔醇、甲硅烷基醚和缩醛。这些方法的合成价值已通过实现低催化剂负载的克级合成得到证明。

  DOI：

  10.1002/anie.201912803

文献信息

• [EN] SUBSTITUTED IMIDAZOTRIAZINES<br/>[FR] IMIDASOTRIAZINES SUBSTITUÉES
  申请人：CONCERT PHARMACEUTICALS INC

  公开号：WO2011011712A1

  公开（公告）日：2011-01-27

  This invention relates to novel substituted imidazotriazines and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a compound showing partial-agonist activity at the GABA α2, α3 and α5 subtype receptors, and antagonist activity at the αl subtype receptor.

  这项发明涉及新型取代咪唑三嗪及其药用盐。该发明还提供了包括本发明化合物的组合物，并将这种组合物用于治疗通过给予显示GABA α2、α3和α5亚型受体部分激动剂活性和α1亚型受体拮抗活性的化合物有益治疗的疾病和症状的方法。
• Increasing metabolic stability via the deuterium kinetic isotope effect: An example from a proline-amide-urea aminothiazole series of phosphatidylinositol-3 kinase alpha inhibitors
  作者：Robin A. Fairhurst、Giorgio Caravatti、Vito Guagnano、Reiner Aichholz、Joachim Blanz、Francesca Blasco、Peter Wipfli、Christine Fritsch、Sauveur-Michel Maira、Christian Schnell、Frank H. Seiler

  DOI：10.1016/j.bmcl.2016.08.041

  日期：2016.10

  In vitro metabolic identification studies with a PI3K-α inhibitor lead molecule 1 identified a single predominant site of oxidative metabolism to be occurring within a tert.butyl moiety. Modification of the tert.butyl group within the lead molecule 1, to the corresponding d9-tert.butyl analogue 2, led to an increase in both the in vitro and in vivo metabolic stability. This increase in metabolic stability

  用PI3K-α抑制剂前导分子1进行的体外代谢鉴定研究确定了氧化代谢的一个主要位点发生在叔丁基部分内。铅分子1中的叔丁基被修饰为相应的d9-叔丁基类似物2，导致体内和体外代谢稳定性均得到提高。与1相比，这种代谢稳定性的提高导致在大鼠中测得的口服生物利用度提高了2倍，而在小鼠的长期体内研究中，其口服生物利用度的提高了3倍。
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：NOVARTIS AG

  公开号：WO2010029082A1

  公开（公告）日：2010-03-18

  The present invention relates to a compound of formula (I) (I) or a salt thereof, wherein the substituents are as defined in the description, to compositions and use of the compounds in the treatment of diseases ameloriated by inhibition of phosphatidylinositol 3-kinase.

  本发明涉及一种式（I）（I）的化合物或其盐，其中取代基如描述中所定义，以及所述化合物在治疗通过抑制磷脂酰肌醇3-激酶改善的疾病中的应用。
• Design and synthesis of deuterated boceprevir analogs with enhanced pharmacokinetic properties
  作者：Adam J. Morgan、Sophia Nguyen、Vinita Uttamsingh、Gary Bridson、Scott Harbeson、Roger Tung、Craig E. Masse

  DOI：10.1002/jlcr.1905

  日期：2011.7

  As part of an ongoing effort to apply the Deuterated Chemical Entity Platform (DCE Platform™) to clinically validated drugs, the synthesis of deuterated analogs of the hepatitis C virus protease inhibitor boceprevir was carried out. The devised synthetic routes allowed for site-selective deuterium incorporation with high levels of isotopic purity. Application of the DCE Platform™ to boceprevir enabled the identification of several deuterated analogs that display marked levels of in vitro metabolic stabilization. Most notably, analog 1g exhibits a near doubling of in vitro half-life in human liver microsomal assays. The details of the convergent synthetic route to the boceprevir isotopologs and the results of the metabolic stability assays are described herein.

  作为将氘代化学实体平台（DCE Platform™）应用于临床验证药物的持续努力的一部分，合成了丙型肝炎病毒蛋白酶抑制剂博切瑞韦的氘代类似物。设计的合成路线允许高水平的同位素纯度进行位点选择性氘掺入。将DCE平台™应用于博切瑞韦，使得能够识别出几种显示出显著体外代谢稳定性的氘代类似物。尤其值得注意的是，类似物1g在人体肝微粒体试验中表现出体外半衰期几乎翻倍。本文中详细描述了博切瑞韦同位素类的收敛合成路线及其代谢稳定性测试的结果。
• Generation of Alkyl Radical through Direct Excitation of Boracene-Based Alkylborate
  作者：Yukiya Sato、Kei Nakamura、Yuto Sumida、Daisuke Hashizume、Takamitsu Hosoya、Hirohisa Ohmiya

  DOI：10.1021/jacs.0c04456

  日期：2020.6.3

  The generation of tertiary, secondary, and primary alkyl radicals has been achieved by the direct visible-light excita-tion of a boracene-based alkylborate. This system is based on the photophysical properties of the organoboron mole-cule. The protocol is applicable to decyanoalkylation, Giese addition, and nickel-catalyzed carbon-carbon bond for-mations such as alkyl-aryl cross-coupling or vicinal

  叔、仲和伯烷基自由基的产生是通过硼苯基烷基硼酸酯的直接可见光激发来实现的。该系统基于有机硼分子的光物理特性。该协议适用于脱氰烷基化、Giese 加成和镍催化的碳-碳键形成，例如烯烃的烷基-芳基交叉偶联或邻位烷基芳基化，从而能够将各种 C(sp3) 片段引入到有机分子。