tert-butyl (1R,2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-hydroxypropan-2-ylcarbamate | 1448423-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: tert-butyl (1R,2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-hydroxypropan-2-ylcarbamate
• 英文别名: tert-butyl N-[(1R,2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-hydroxypropan-2-yl]carbamate
• CAS: 1448423-16-2
• 化学式: C₁₅H₂₃N₃O₃
• 分子量: 293.366
• InChiKey: LOGYPVBHBCVURI-CABZTGNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-hydroxypropan-2-ylcarbamate 在 盐酸 、 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.08h， 生成 N-((1R,2S)-1-(2-bromo-4-cyanophenoxy)-1-(2-cyclopropylpyrimidin-5-yl)propan-2-yl)-2,2-difluoropropanamide
  参考文献：
  名称：

  Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile

  摘要：

  Synthetic glucocorticoids (GC) are essential for the treatment of a broad range of inflammatory diseases. However, their use is limited by target related adverse effects on, e.g., glucose homeostasis and bone metabolism. Starting from a nonsteroidal GR ligand (4) that is a full agonist in reporter gene assays, we exploited key functional triggers within the receptor, generating a range of structurally diverse partial agonists. Of these, only a narrow subset exhibited full anti-inflammatory efficacy and a significantly reduced impact on adverse effect markers in human cell assays compared to prednisolone. This led to the discovery of AZD9567 (15) with excellent in vivo efficacy when dosed orally in a rat model of joint inflammation. Compound 15 is currently being evaluated in clinical trials comparing the efficacy and side effect markers with those of prednisolone.

  DOI：

  10.1021/acs.jmedchem.7b01690
• 作为产物：
  描述：

  tert-butyl [(2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-oxopropan-2-yl]carbamate 在 aluminum isopropoxide 、 异丙醇 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以777 mg的产率得到tert-butyl (1R,2S)-1-(2-cyclopropylpyrimidin-5-yl)-1-hydroxypropan-2-ylcarbamate
  参考文献：
  名称：

  Enantiomeric purity determination by NMR: proving the purity of a single enantiomer

  摘要：

  The NMR spectra of separate samples of an analyte complexed with each enantiomer of a chiral solvating agent (CSA) give an accurate estimate of the chemical shifts of racemic analytes in the presence of a single enantiomer of the CSA. This effect allows a CSA-based chiral NMR method to be developed when only a single enantiomer of analyte is available. The ability to develop a method capable of discriminating between enantiomers in these circumstances is useful, for example, to resolve the question of whether racemization has occurred during the synthesis of a chiral molecule. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.05.014