(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,3-dihydro-1H-indole | 321744-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,3-dihydro-1H-indole
• 英文别名: (S)-2-(((tert-butyldimethylsilyl)oxy)methyl)indoline；(S)-2-[(tert-butyldimethylsilyloxy)methyl]indoline；(S)-2-tert-butyldimethylsilyloxymethylindoline；tert-butyl-[[(2S)-2,3-dihydro-1H-indol-2-yl]methoxy]-dimethylsilane
• CAS: 321744-15-4
• 化学式: C₁₅H₂₅NOSi
• 分子量: 263.455
• InChiKey: ZJAGAFMGKUWIRF-ZDUSSCGKSA-N

物化性质

• 沸点：
  325.2±11.0 °C(Predicted)
• 密度：
  0.951±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,3-dihydro-1H-indole 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 lithium hydroxide monohydrate 、 20% palladium hydroxide-activated charcoal 、 水 、 氢气 、 碘 、 碳酸氢钠 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 138.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and biological activities of novel hexahydropyrazino[1,2-a]indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with improved membrane permeability across MDR1 expressing cells

  摘要：

  We previously reported octahydropyrrolo[1,2-a]pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino[1,2-a]indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve the membrane permeability across MDR1 expressing cells. We established a chiral pool synthetic route to yield the desired tricyclic chiral isomers. Chemical modification of the core scaffold led to a representative compound 50, which showed strong inhibition of IAP binding (X chromosome-linked IAP [XIAP]: IC50 23 nM and cellular IAP [cIAP]: IC50 1.1 nM) and cell growth inhibition (MDA-MB-231 cells: GI50 2.8 nM) with high permeability and low potential of MDR1 substrate.

  DOI：

  10.1016/j.bmc.2013.09.067
• 作为产物：
  描述：

  (S)-吲哚啉-2-羧酸 在 咪唑 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Design, synthesis, and biological activities of novel hexahydropyrazino[1,2-a]indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with improved membrane permeability across MDR1 expressing cells

  摘要：

  We previously reported octahydropyrrolo[1,2-a]pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino[1,2-a]indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve the membrane permeability across MDR1 expressing cells. We established a chiral pool synthetic route to yield the desired tricyclic chiral isomers. Chemical modification of the core scaffold led to a representative compound 50, which showed strong inhibition of IAP binding (X chromosome-linked IAP [XIAP]: IC50 23 nM and cellular IAP [cIAP]: IC50 1.1 nM) and cell growth inhibition (MDA-MB-231 cells: GI50 2.8 nM) with high permeability and low potential of MDR1 substrate.

  DOI：

  10.1016/j.bmc.2013.09.067

文献信息

• Kinetic Resolution of 2-Substituted Indolines by <i>N</i> -Sulfonylation using an Atropisomeric 4-DMAP-<i>N</i> -oxide Organocatalyst
  作者：James I. Murray、Nils J. Flodén、Adriano Bauer、Nico D. Fessner、Daniel L. Dunklemann、Opetoritse Bob-Egbe、Henry S. Rzepa、Thomas Bürgi、Jeffery Richardson、Alan C. Spivey

  DOI：10.1002/anie.201700977

  日期：2017.5.15

  The first catalytic kinetic resolution by N‐sulfonylation is described. 2‐Substituted indolines are resolved (s=2.6–19) using an atropisomeric 4‐dimethylaminopyridine‐N‐oxide (4‐DMAP‐N‐oxide) organocatalyst. Use of 2‐isopropyl‐4‐nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model

  描述了通过N-磺酰化的第一个催化动力学拆分。使用阻转异构的4-二甲基氨基吡啶-N-氧化物（4-DMAP-N-氧化物）有机催化剂可拆分2-取代的二氢吲哚（s = 2.6–19）。使用2-异丙基-4-硝基苯磺酰氯对于立体鉴别至关重要，并且可以使磺酰胺产品与巯基乙酸轻松脱保护。提出了解释立体歧视的定性模型。
• Free and Cr(CO)₃-Complexed Aminophosphine Phosphinite Ligands for Highly Enantioselective Hydrogenation of α-Functionalized Ketones
  作者：Corinne Pasquier、Said Naili、André Mortreux、Francine Agbossou、Lydie Pélinski、Jacques Brocard、Jürgen Eilers、Iris Reiners、Viola Peper、Jürgen Martens

  DOI：10.1021/om0006312

  日期：2000.12.1

  stereoelectronic effects generated by the presence of the tricarbonyl chromium moiety onto the hydrogenations have been assessed. The beneficial effect of the matching chiralities in ligand syn-12 associated with the use of the most appropriate nonchiral ligand Cl has resulted in a win of 13% of ee for the rhodium-based hydrogenation of 15. While using the most suitable new chiral AMPP ligand from this study

  的一系列新芳基-和环烷基取代的氨基膦次膦酸酯（的合成和表征1 - 8）从三个前体（反应得到小号）-2-羟甲氮杂环丁烷，（小号）-3-羟甲基-1,2-描述了，3，4-四氢异喹啉和（S）-2-羟甲基吲哚啉和氯膦。在芳族环（小号）-2- hydroxymethylindoline已经允许的合成和分离三羰基铬络合氨基醇顺-10和反-10，其类似地转化成相应的氨基膦次膦酸酯11 - 13，具有立体感中心和平面手性。配体5（（S）-Cp，Cp-IndoNOP）揭示了前所未有的31 P NMR通量行为，与P-杂原子（N和O）键周围的旋转抑制有关。这些新的AMPP配体用于各种α-官能化酮的对映选择性加氢，即二氢-4,4-二甲基-2,3-呋喃二酮14，N-苄基苯甲酰甲酰胺15，丙酮酸乙酯16和2-（N，N -二甲基）氨基苯乙酮盐酸盐17。已经评估了由三羰基铬部分的存在对氢化产生的立体电子效应。在配位体的手性
• Kinetic Resolutions of Indolines by a Nonenzymatic Acylation Catalyst
  作者：Forrest O. Arp、Gregory C. Fu

  DOI：10.1021/ja0657859

  日期：2006.11.1

  The first method for the kinetic resolution of indolines through catalytic N-acylation is described. To improve the selectivity factor, new planar-chiral PPY-derived catalysts were synthesized, wherein the chiral environment was systematically modified. This work provides a rare example of a nonenzyme-based acylation catalyst for the kinetic resolution of amines.
• US11628223
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis, and biological activities of novel hexahydropyrazino[1,2-a]indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with improved membrane permeability across MDR1 expressing cells
  作者：Zenyu Shiokawa、Kentaro Hashimoto、Bunnai Saito、Yuya Oguro、Hiroyuki Sumi、Masato Yabuki、Mie Yoshimatsu、Yohei Kosugi、Yasuyuki Debori、Nao Morishita、Douglas R. Dougan、Gyorgy P. Snell、Sei Yoshida、Tomoyasu Ishikawa

  DOI：10.1016/j.bmc.2013.09.067

  日期：2013.12

  We previously reported octahydropyrrolo[1,2-a]pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino[1,2-a]indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve the membrane permeability across MDR1 expressing cells. We established a chiral pool synthetic route to yield the desired tricyclic chiral isomers. Chemical modification of the core scaffold led to a representative compound 50, which showed strong inhibition of IAP binding (X chromosome-linked IAP [XIAP]: IC50 23 nM and cellular IAP [cIAP]: IC50 1.1 nM) and cell growth inhibition (MDA-MB-231 cells: GI50 2.8 nM) with high permeability and low potential of MDR1 substrate.