(S)-3-((tert-butyldimethylsilyl)oxy)-N-methoxy-N-methylbutanamide | 351458-95-2

• 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: (S)-3-((tert-butyldimethylsilyl)oxy)-N-methoxy-N-methylbutanamide
• 英文别名: (S)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylbutyramide；(S)-N-methoxy-N-methyl-3-tert-butyldimethylsilyloxybutyramide；(3S)-3-[tert-butyl(dimethyl)silyl]oxy-N-methoxy-N-methylbutanamide
• CAS: 351458-95-2
• 化学式: C₁₂H₂₇NO₃Si
• 分子量: 261.437
• InChiKey: SPWYQOFPTZBOJN-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-3-((tert-butyldimethylsilyl)oxy)-N-methoxy-N-methylbutanamide 在 palladium diacetate 四氯化硅 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 (4S)-4-(tert-butyldimethylsilyloxy)-2-trichlorosilyloxy-1-pentene
  参考文献：
  名称：

  Lewis碱中遥远的立体中心的影响催化了手性三氯甲硅烷基烯醇酸酯的羟醛加成。

  摘要：

  在磷酰胺催化的醛醇缩合反应中采用带有较远的立体生成中心的手性三氯甲硅烷基烯醇盐。甲基酮烯酸酯的添加仅具有中等的非对映选择性。将Z-烯酸酯添加到各种醛中选择性地产生了顺式相对非对映异构体。在这两种情况下，β-甲硅烷氧基立体异构中心的作用均不明显，内部非对映异构主要由催化剂控制。[反应：看文字]

  DOI：

  10.1021/ol026594n
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 咪唑 、 异丙基氯化镁 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 19.0h， 生成 (S)-3-((tert-butyldimethylsilyl)oxy)-N-methoxy-N-methylbutanamide
  参考文献：
  名称：

  Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions

  摘要：

  We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.

  DOI：

  10.1021/acs.jmedchem.7b01927

文献信息

• TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE
  申请人：Hutchinson John Howard

  公开号：US20070173508A1

  公开（公告）日：2007-07-26

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物抑制5-脂氧合酶（5-LO）的活性。本文还描述了使用这种5-LO抑制剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的状况、疾病或紊乱。
• Approaches to 2-substituted chroman-4-ones: synthesis of (−)-pinostrobin
  作者：Kevin J Hodgetts

  DOI：10.1016/s0040-4039(01)00567-6

  日期：2001.5

  Two approaches to optically active 2-substituted chroman-4-ones are described. The first utilized the oxidation of a preformed chroman ring and the second an intramolecular Mitsunobu cyclization. The methodology was applied to the synthesis of the biologically active natural product (−)-pinostrobin (18).

  描述了两种光学活性的2-取代的苯并吡喃-4-酮的方法。第一种利用预先形成的苯并二氢吡喃环的氧化，第二种利用分子内光延环化。该方法被应用于生物活性天然产物（-）-pinostrobin（18）的合成。
• Routes for the Synthesis of (2<i>S</i>)-2-Methyltetrahydropyran-4-one from Simple Optically Pure Building Blocks
  作者：Kevin R. Anderson、Stéphanie L. G. Atkinson、Takahiro Fujiwara、Melvyn E. Giles、Takaji Matsumoto、Eric Merifield、John T. Singleton、Takao Saito、Tsukasa Sotoguchi、James A. Tornos、Edward L. Way

  DOI：10.1021/op900163a

  日期：2010.1.15

  Routes to (2S)-2-methyltetrahydropyran-4-one of high optical purity starting from readily available chiral pool precursors and suitable for large-scale manufacture are described. In one approach, the key step is cyclisation of (S)-5-hydroxyhex-1-en-3-one, derived either from an alkyl (S)-3-hydroxybutyrate or (S)-propylene oxide. Formation of the tetrahydropyran ring directly via an intramolecular oxy-Michael

  描述了从容易获得的手性库前体开始并适于大规模生产的具有高光学纯度的（2S）-2-甲基四氢吡喃-4-酮的途径。在一种方法中，关键步骤是衍生自（S）-3-羟基丁酸烷基酯或（S）-环氧丙烷的（S）-5-羟基己-1-烯-3-酮的环化。在酸催化条件下直接通过分子内的氧-迈克尔反应形成四氢吡喃环导致光学纯度的损失，而通过中间体（2 S）-2-甲基-2,3-二氢吡喃-4-酮经由氧化的Pd催化的闭环反应，随后烯基键的氢化反应，保留了光学纯度。还报道了（2 S）-2-甲基-2,3-二氢吡喃-4-酮的另一种方法，该方法再次从（S）-3-羟基丁酸烷基酯精制为羰基保护的（6 S）- 6-甲基-5,6-二氢吡喃-2,4-二酮衍生物，然后部分还原并脱水。或者，可以在一步保护中将羰基完全还原掉，从而在脱保护后直接提供（2 S）-2-甲基四氢吡喃-4-酮。
• Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions
  作者：Wensheng Yu、Ling Tong、Oleg Selyutin、Lei Chen、Bin Hu、Bin Zhong、Jinglai Hao、Tao Ji、Shuai Zan、Jingjun Yin、Rebecca T. Ruck、Stephanie Curry、Patricia McMonagle、Sony Agrawal、Laura Rokosz、Donna Carr、Paul Ingravallo、Karin Bystol、Frederick Lahser、Rong Liu、Shiying Chen、Kung-I Feng、Mark Cartwright、Ernest Asante-Appiah、Joseph A. Kozlowski

  DOI：10.1021/acs.jmedchem.7b01927

  日期：2018.5.10

  We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.
• The Effects of a Remote Stereogenic Center in the Lewis Base Catalyzed Aldol Additions of Chiral Trichlorosilyl Enolates
  作者：Scott E. Denmark、Shinji Fujimori

  DOI：10.1021/ol026594n

  日期：2002.10.1

  Chiral trichlorosilyl enolates bearing a remote stereogenic center were employed in the phosphoramide-catalyzed aldol reaction. The additions of the methyl ketone enolates proceeded with only moderate diastereoselectivities. The addition of the Z-enolate to various aldehydes selectively produced the syn relative diastereomers. In both cases, the effect of the beta-silyloxy stereogenic center was modest

  在磷酰胺催化的醛醇缩合反应中采用带有较远的立体生成中心的手性三氯甲硅烷基烯醇盐。甲基酮烯酸酯的添加仅具有中等的非对映选择性。将Z-烯酸酯添加到各种醛中选择性地产生了顺式相对非对映异构体。在这两种情况下，β-甲硅烷氧基立体异构中心的作用均不明显，内部非对映异构主要由催化剂控制。[反应：看文字]