1-bromo-2-(methoxy-d₃)benzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-bromo-2-(methoxy-d₃)benzene
• 英文别名: 2-(Methoxy-d3)-bromobenzene；1-bromo-2-(trideuteriomethoxy)benzene
• 化学式: C₇H₇BrO
• 分子量: 190.012
• InChiKey: HTDQSWDEWGSAMN-FIBGUPNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-bromo-2-(methoxy-d₃)benzene 在 2-双环己基膦-2',6'-二甲氧基联苯 、 双(乙腈)氯化钯(II) 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 6.0h， 生成 (S)-2-((6-(2-(methoxy-d₃)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol
  参考文献：
  名称：

  Balancing potency, metabolic stability and permeability in pyrrolopyrimidine-based EGFR inhibitors

  摘要：

  The present study describes our continuous effort to develop epidermal growth factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4-amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new structures, including four variations of the 4-amino group and 34 different substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines were highly active, with twelve analogues possessing lower IC50 values than the commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also profiled in cell studies using the Ba/F3-EGFR(L858R) reporter cells, and all revealed nanomolar activity. However, some of the privileged structures in terms of potency had ADME short-comings: compounds containing amides, sulfonamides, amine and hydroxymethyl substituents in the 6-aryl group had low permeability and high efflux, derivatives having (R)-3amino-3-phenylpropan-1-ol at C-4 induced hERG inhibition properties, and metabolic lability was seen for compounds having (S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)amino)ethan-1-ol appeared as the most promising drug candidate. Cellular studies indicate this compound to have therapeutic use in EGFR driven diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.068
• 作为产物：
  描述：

  氘代碘甲烷 、 2-溴苯酚 在 potassium hydroxide 作用下， 以 乙腈 为溶剂， 反应 40.5h， 生成 1-bromo-2-(methoxy-d₃)benzene
  参考文献：
  名称：

  Alkali-Metal- and Alkaline-Earth-Metal-Mediated C–O Activation of an Anisole-Substituted Phosphido–Borane Ligand

  摘要：

  The reaction between {(Me3Si)(2)CH}PH(C6H4-2-OMe) (4) and 1 equiv of BH3 center dot SMe2 yields the phosphine-borane {(Me3Si)(2)CH}PH(BH3)(C6H4-2-OMe) (5). Subsequent reaction between 5 and 1 equiv of n-BuLi in THF gives the phosphido-borane complex [{(Me3Si)(2)CH}P(BH3) (C6H4-2-OMe)]Li(THF) (6a), which was isolated as a colorless microcrystalline solid. Treatment of 5 with 1 equiv of PhCH2M yields the corresponding complexes [{(Me3Si)(2)CH}P(BH3)(C6H4-2-OMe)]ML (ML = Na-(THF) (6b), K(pmdeta) (6c); pmdeta = N,N,N',N '',N ''-pentamethyldiethylenetriamine), after crystallization in the presence of the corresponding coligand. While compounds 6b,c are stable toward heat, compound 6a decomposes on heating to 50 degrees C in toluene to give the cluster [[{(Me3Si)(2)CH}PH(C6H4-2-O)]Li](6) (7) and the tertiary phosphine borane {(Me3Si)(2)CH}P(BH3)(Me)(C6H4-2-OMe) (8). Related C-O cleavage reactions are observed when MgI2 is treated with 2 equiv of 6a and when CaI2 is treated with 2 equiv of [{(Me3Si)(2)CH}P(BH3)(C6H4-2-OMe)]K in THF, giving [{(Me3Si)(2)CH}P(BH3)(C6H4-2-O)Mg(THF)(2)](2) (9) and [{(Me3Si)(2)CH}P(BH3)(C6H4-2-O)Ca(THF)](4) (10), respectively, along with 1 equiv of 8 in each case. In contrast, the reaction between SrI2 and 2 equiv of [{(Me3Si)(2)CH}P(BH3)(C6H4-2-OMe)]K in THF yields [{(Me3Si)(2)CH}P(BH3)(C6H4-2-OMe)Sr(THF)(4)] (11).

  DOI：

  10.1021/acs.organomet.7b00262

文献信息

• Trideuteromethylation Enabled by a Sulfoxonium Metathesis Reaction
  作者：Zuyuan Shen、Shilei Zhang、Huihui Geng、Jiarui Wang、Xinyu Zhang、Anqi Zhou、Cheng Yao、Xiaobei Chen、Wei Wang

  DOI：10.1021/acs.orglett.8b03641

  日期：2019.1.18

  A conceptually novel sulfoxonium metathesis reaction between TMSOI and cost-effective DMSO-d6 is developed for the efficient generation of a new trideuteromethylation reagent TDMSOI. The new reagent TDMSOI is produced highly efficiently by simply heating a mixture of TMSOI and DMSO-d6 and directly used for subsequent trideuteromethylation in a “one-pot” operation. The preparative power of the new versatile

  TMSOI 和经济高效的 DMSO- d 6之间的概念上新颖的硫鎓复分解反应被开发出来，用于有效生成新型三氘代甲基化试剂 TDMSOI。新试剂TDMSOI只需加热TMSOI和DMSO- d 6的混合物即可高效生产，并直接用于后续的“一锅”操作中的三氘代甲基化。新的多功能试剂和“一锅”方案的制备能力通过其以高产率和有用的方式将-CD 3部分安装到广泛的功能中而得到证明，包括苯酚、苯硫酚、酸性胺和烯醇化亚甲基单元。氘化水平 (>87% D)。
• Development of a Potent Nurr1 Agonist Tool for In Vivo Applications
  作者：Jan Vietor、Christian Gege、Tanja Stiller、Romy Busch、Espen Schallmayer、Hella Kohlhof、Georg Höfner、Jörg Pabel、Julian A. Marschner、Daniel Merk

  DOI：10.1021/acs.jmedchem.3c00415

  日期：2023.5.11