tert-butyl(dimethyl)(4-nitrobutoxy)silane

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: tert-butyl(dimethyl)(4-nitrobutoxy)silane
• 英文别名: 1-(tert-butyldimethylsilyloxy)-4-nitrobutane；Tert-butyl-dimethyl-(4-nitrobutoxy)silane
• 化学式: C₁₀H₂₃NO₃Si
• 分子量: 233.383
• InChiKey: VPUHZSHPIBGZKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl(dimethyl)(4-nitrobutoxy)silane 在 N-benzyl quinidinium chloride 、 cesiumhydroxide monohydrate 、 sodium nitrite 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 52.0h， 生成 (R)-(-)-tert-butyl 5-(tert-butyldimethylsilyloxy)-2-oxo-1-phenylpentylcarbamate
  参考文献：
  名称：

  A concise enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate using catalytic enantioselective aza-Henry reaction as key step

  摘要：

  An efficient enantioselective synthesis of L-(-)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate is accomplished by means of catalytic enantioselective aza-Henry reaction. A key feature of this protocol is organocatalysis as genesis of chirality to ensure high degree of distereo- and enantiocontrol. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.02.031
• 作为产物：
  描述：

  4-(叔丁基二甲基甲硅烷基)氧代-1-丁醇 在 咪唑 、 silver(I) nitrite 、 碘 、 三苯基膦 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 48.0h， 生成 tert-butyl(dimethyl)(4-nitrobutoxy)silane
  参考文献：
  名称：

  Discovery of Isoxazole Analogues of Sazetidine-A as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists for the Treatment of Depression

  摘要：

  Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the alpha 4 beta 2 subtype of nAChR over alpha 3 beta 4-nAChRs are partial agonists at the alpha 4 beta 2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline.

  DOI：

  10.1021/jm200855b

文献信息

• Catalytic Asymmetric Syntheses of ICI-199441 and CP-99994 Using Nitro-Mannich Reaction
  作者：Natsuko Tsuritani、Ken-ichi Yamada、Naoki Yoshikawa、Masakatsu Shibasaki

  DOI：10.1246/cl.2002.276

  日期：2002.3

  Catalytic asymmetric syntheses of ICI-199441 and CP-99994 were achieved using the nitro-Mannich reaction as a key step.

  以硝基-曼尼希反应为关键步骤，实现了 ICI-199441 和 CP-99994 的催化不对称合成。
• Discovery of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists Containing an Isoxazolylpyridine Ether Scaffold that Demonstrate Antidepressant-like Activity. Part II
  作者：Li-Fang Yu、J. Brek Eaton、Allison Fedolak、Han-Kun Zhang、Taleen Hanania、Dani Brunner、Ronald J. Lukas、Alan P. Kozikowski

  DOI：10.1021/jm301177j

  日期：2012.11.26

  In our continued efforts to develop alpha 4 beta 2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certam isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [H-3]epibatidine binding studies together with functional assays based on Rb-86(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.
• Discovery of Isoxazole Analogues of Sazetidine-A as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists for the Treatment of Depression
  作者：Jianhua Liu、Li-Fang Yu、J. Brek Eaton、Barbara Caldarone、Katie Cavino、Christina Ruiz、Matthew Terry、Allison Fedolak、Daguang Wang、Afshin Ghavami、David A. Lowe、Dani Brunner、Ronald J. Lukas、Alan P. Kozikowski

  DOI：10.1021/jm200855b

  日期：2011.10.27

  Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the alpha 4 beta 2 subtype of nAChR over alpha 3 beta 4-nAChRs are partial agonists at the alpha 4 beta 2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline.
• A concise enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate using catalytic enantioselective aza-Henry reaction as key step
  作者：Gullapalli Kumaraswamy、Arigala Pitchaiah

  DOI：10.1016/j.tet.2011.02.031

  日期：2011.4

  An efficient enantioselective synthesis of L-(-)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate is accomplished by means of catalytic enantioselective aza-Henry reaction. A key feature of this protocol is organocatalysis as genesis of chirality to ensure high degree of distereo- and enantiocontrol. (C) 2011 Elsevier Ltd. All rights reserved.