(3S)-3-[(tert-butyldimethylsilyl)oxy]-4-chlorobutanenitrile | 884902-55-0

• 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: (3S)-3-[(tert-butyldimethylsilyl)oxy]-4-chlorobutanenitrile
• 英文别名: (3S)-3-(tert-butyldimethylsiloxy)-4-chlorobutanenitrile；(S)-3-[(tert-Butyldimethylsilyl)oxy]-4-chlorobutanenitrile；(3S)-3-[tert-butyl(dimethyl)silyl]oxy-4-chlorobutanenitrile
• CAS: 884902-55-0
• 化学式: C₁₀H₂₀ClNOSi
• 分子量: 233.813
• InChiKey: CLSDDCUBUAXIFQ-VIFPVBQESA-N

物化性质

• 沸点：
  279.1±20.0 °C(Predicted)
• 密度：
  0.970±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.53
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-3-[(tert-butyldimethylsilyl)oxy]-4-chlorobutanenitrile 在 platinum on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-phenylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 2: The design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP

  摘要：

  The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s < 10 nM. Ancillary hERG activity was evaluated for this series of inhibitors. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.030
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 (S)-4-氯-3-羟基丁腈 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到(3S)-3-[(tert-butyldimethylsilyl)oxy]-4-chlorobutanenitrile
  参考文献：
  名称：

  [EN] INDAZOLES
  [FR] INDAZOLES

  摘要：

  该发明提供了根据式（I）制备的新型取代吲唑化合物，其用于治疗高增殖性疾病，如癌症、炎症或退行性疾病。

  公开号：

  WO2016026549A1

文献信息

• Tandem One-Pot Construction of Indoles via Palladium and Copper-Catalyzed Coupling Reactions of the Blaise Reaction Intermediate
  作者：Sang-gi Lee、Ju Kim

  DOI：10.1055/s-0031-1289753

  日期：2012.5

  Chemoselective Intramolecular N-Alkylation/Palladium-Catalyzed C-N Coupling Reaction of the Blaise Reaction Intermediate 2.3 Copper-Catalyzed Intermolecular N-C/C-C Coupling Reaction of the Blaise Reaction Intermediate with 1,2-Dihaloarenes 3 Conclusion tandem reaction - Blaise reaction - palladium - copper - coupling - indoles

  通过腈与α-溴-α-（2-溴苯基）乙酸乙酯和锌的原位生成的Reformatsky试剂的反应形成的Blaise反应中间体的钯催化的分子内N-芳基化反应，可高收率地提供吲哚。这种方法扩展到具有ω-氯烷基附件的Blaise反应中间体的化学选择性分子内N-烷基化/钯催化的N-芳基化，为串联一锅法合成N稠合的吲哚衍生物提供了一条新途径。相反，在钯催化剂的存在下，Blaise反应中间体与1,2-二卤代苯的分子间偶联反应没有进行，但是在碘化铜（I）作为催化剂的存在下进行并产生了吲哚。 1引言 2结果与讨论 2.1 Blaise反应中间体的钯催化分子内CN偶联反应 2.2 Blaise反应中间体的化学选择性分子内N-烷基化/钯催化的CN偶联反应 2.3铜催化的布莱斯反应中间体与1,2-二卤代芳烃的分子间NC / CC偶联反应 3结论 串联反应-布莱斯反应-钯-铜-偶联-吲哚
• Chemoselective Intramolecular Alkylation of the Blaise Reaction Intermediates: Tandem One-Pot Synthesis of <i>exo</i>-Cyclic Enaminoesters and Their Applications toward the Synthesis of <i>N</i>-Heterocyclic Compounds
  作者：Ju Hyun Kim、Hyunik Shin、Sang-gi Lee

  DOI：10.1021/jo201964a

  日期：2012.2.3

  The intramolecular alkylative reactivity and N/C selectivity of the various Blaise reaction intermediates, which are formed from the reaction of the Reformatsky reagents with omega-chloroalkyl nitriles, did not reach the synthetic potential as an entry to exo-cyclic enaminoesters. To circumvent this issue, various additives were investigated, among which the addition of NaHMDS dramatically enhanced the reactivity and N/C selectivity. This modification provided a highly efficient route for the synthesis of various N-fused heterocyclic compounds, as it requires only two steps from nitriles.
• [EN] INDAZOLES<br/>[FR] INDAZOLES
  申请人：MERCK PATENT GMBH

  公开号：WO2016026549A1

  公开（公告）日：2016-02-25

  The invention provides novel substituted indazole compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.

  该发明提供了根据式（I）制备的新型取代吲唑化合物，其用于治疗高增殖性疾病，如癌症、炎症或退行性疾病。
• Kinesin spindle protein (KSP) inhibitors. Part 2: The design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP
  作者：Mark E. Fraley、Robert M. Garbaccio、Kenneth L. Arrington、William F. Hoffman、Edward S. Tasber、Paul J. Coleman、Carolyn A. Buser、Eileen S. Walsh、Kelly Hamilton、Christine Fernandes、Michael D. Schaber、Robert B. Lobell、Weikang Tao、Victoria J. South、Youwei Yan、Lawrence C. Kuo、Thomayant Prueksaritanont、Cathy Shu、Maricel Torrent、David C. Heimbrook、Nancy E. Kohl、Hans E. Huber、George D. Hartman

  DOI：10.1016/j.bmcl.2006.01.030

  日期：2006.4

  The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s < 10 nM. Ancillary hERG activity was evaluated for this series of inhibitors. (C) 2006 Elsevier Ltd. All rights reserved.