(R)-3-O-(tert-butyldimethylsilyl)-N-methoxy-N-methylbutanamide | 245107-73-7

• 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: (R)-3-O-(tert-butyldimethylsilyl)-N-methoxy-N-methylbutanamide
• 英文别名: (R)-3-((tert-butyldimethylsilyl)oxy)-N-methoxy-N-methylbutanamide；(R)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylbutanamide；(3R)-3-[tert-butyl(dimethyl)silyl]oxy-N-methoxy-N-methylbutanamide
• CAS: 245107-73-7
• 化学式: C₁₂H₂₇NO₃Si
• 分子量: 261.437
• InChiKey: SPWYQOFPTZBOJN-SNVBAGLBSA-N

物化性质

• 沸点：
  269.3±42.0 °C(Predicted)
• 密度：
  0.934±0.06 g/cm3(Predicted)

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：

  (R)-3-O-(tert-butyldimethylsilyl)-N-methoxy-N-methylbutanamide 在 lithium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 cerium(III) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 为溶剂， 反应 8.5h， 生成 (2S,4S,5S,8R,10R)-10-O-(tert-butyldimethylsilyl)-8-hydroxy-1,2:4,5-di-(isopropylidenedioxy)-6-undecene
  参考文献：
  名称：

  Synthesis and biological testings as inhibitors of HMGCoA reductase of the seco-acid of tuckolide and its C-7 epimer

  摘要：

  The seco-acid of the natural macrolactone, tuckolide (decarestrictin D) and the C-7 epimer have been prepared in enantiomerically pure form from D-gluconolactone and poly(3-hydroxy butyric acid). The key steps are Horner-Emmons olefination and stereoselective reduction of the resulting enone to provide both epimers at C-7. None of the seco-acids inhibit microsomal HMGCoA reductase of pea or rat liver. It may be concluded that the cholesterol biosynthesis inhibiting effect of tuckolide is unlikely to proceed via HMGCoA reductase inhibition. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00020-6
• 作为产物：
  描述：

  benzyl (R)-(-)-3-(tert-butyldimethylsilyloxy)butyrate 在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 生成 (R)-3-O-(tert-butyldimethylsilyl)-N-methoxy-N-methylbutanamide
  参考文献：
  名称：

  Mechanistic Insight with HBCH₂CoA as a Probe to Polyhydroxybutyrate (PHB) Synthases

  摘要：

  Polyhydroxybutyrate (PHB) synthases catalyze the polymerization of 3-(R)-hydroxybutyrate coenzyme A (HBCoA) to produce polyoxoesters of 1-2 MDa. A substrate analogue HBCH2CoA, in which the S in HBCoA is replaced with a CH2 group, was synthesized in 13 steps using a chemoenzymatic approach in a 7.5% overall yield. Kinetic studies reveal it is a competitive inhibitor of a class I and a class III PHB synthases, with Kis of 40 and 14 μM, respectively. To probe the elongation steps of the polymerization, HBCH2CoA was incubated with a synthase acylated with a [(3)H]-saturated trimer-CoA ([(3)H]-sTCoA). The products of the reaction were shown to be the methylene analogue of [(3)H]-sTCoA ([(3)H]-sT-CH2-CoA), saturated dimer-([(3)H]-sD-CO2H), and trimer-acid ([(3)H]-sT-CO2H), distinct from the expected methylene analogue of [(3)H]-saturated tetramer-CoA ([(3)H]-sTet-CH2-CoA). Detection of [(3)H]-sT-CH2-CoA and its slow rate of formation suggest that HBCH2CoA may be reporting on the termination and repriming process of the synthases, rather than elongation.

  DOI：

  10.1021/cb5002735

文献信息

• [EN] HEPATITIS C VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014065791A1

  公开（公告）日：2014-05-01

  The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和用于治疗丙型肝炎病毒（HCV）感染的方法。还公开了含有这些化合物的药物组合物以及使用这些化合物治疗HCV感染的方法。
• A Highly Efficient Synthesis of (—)-Pinidinol
  作者：Siegfried Blechert、Julian Gebauer、Daniel Rost

  DOI：10.3987/com-06-10847

  日期：——

  A short step synthesis of the bioactive piperidine alkaloid (-)-pinidinol was achieved using a cross metathesis and a reductive amination as the key steps.

  使用交叉复分解和还原胺化作为关键步骤，实现了生物活性哌啶生物碱 (-)-pinidinol 的短步合成。
• Hepatitis C Virus Inhibitors
  申请人：Bender John A.

  公开号：US20130028859A1

  公开（公告）日：2013-01-31

  The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和方法，用于治疗丙型肝炎病毒（HCV）感染。还公开了含有这些化合物的制药组合物和使用这些化合物治疗HCV感染的方法。
• Hepatitis C virus inhibitors
  申请人：Bender John A.

  公开号：US08552047B2

  公开（公告）日：2013-10-08

  The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和治疗丙型肝炎病毒（HCV）感染的方法。还公开了包含这些化合物的药物组合物和使用这些化合物治疗HCV感染的方法。
• 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.