(S)-3-benzyl-5-ethoxy-3,6-dihydro-2H-1,4-oxazine | 1162182-68-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-3-benzyl-5-ethoxy-3,6-dihydro-2H-1,4-oxazine
• CAS: 1162182-68-4
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: NOXSOIXDEYNROI-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.06
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  30.82
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-3-benzyl-5-ethoxy-3,6-dihydro-2H-1,4-oxazine 在 氯化铵 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以4.53 g的产率得到
  参考文献：
  名称：

  Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates

  摘要：

  We previously observed a cutaneous type IV immune response in nonhuman primates (NHP) with the mGlu(5) negative allosteric modulator (NAM) 7. To determine if this adverse event was chemotype- or mechanism-based, we evaluated a distinct series of mGlu(5) NAMs. Increasing the sp(3) character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu(5) NAM series. Its prototype, (R)-6-neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c] [1,4]oxazin-4(9H)-one (PF-06462894, 8), possessed favorable properties and a predicted low clinical dose (2 mg twice daily). Compound 8 did not show any evidence of immune activation in a mouse drug allergy model. Additionally, plasma samples from toxicology studies confirmed that 8 did not form any reactive metabolites. However, 8 caused the identical microscopic skin lesions in NHPs found with 7, albeit with lower severity. Holistically, this work supports the hypothesis that this unique toxicity may be mechanism-based although additional work is required to confirm this and determine clinical relevance.

  DOI：

  10.1021/acs.jmedchem.7b00604
• 作为产物：
  描述：

  (S)-2-chloro-N-(1-hydroxy-3-phenylpropan-2-yl)acetamide 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 (S)-3-benzyl-5-ethoxy-3,6-dihydro-2H-1,4-oxazine
  参考文献：
  名称：

  Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates

  摘要：

  We previously observed a cutaneous type IV immune response in nonhuman primates (NHP) with the mGlu(5) negative allosteric modulator (NAM) 7. To determine if this adverse event was chemotype- or mechanism-based, we evaluated a distinct series of mGlu(5) NAMs. Increasing the sp(3) character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu(5) NAM series. Its prototype, (R)-6-neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c] [1,4]oxazin-4(9H)-one (PF-06462894, 8), possessed favorable properties and a predicted low clinical dose (2 mg twice daily). Compound 8 did not show any evidence of immune activation in a mouse drug allergy model. Additionally, plasma samples from toxicology studies confirmed that 8 did not form any reactive metabolites. However, 8 caused the identical microscopic skin lesions in NHPs found with 7, albeit with lower severity. Holistically, this work supports the hypothesis that this unique toxicity may be mechanism-based although additional work is required to confirm this and determine clinical relevance.

  DOI：

  10.1021/acs.jmedchem.7b00604

文献信息

• From Mono-Triazolium Salt to Bis-Triazolium Salt: Improvement of the Asymmetric Intermolecular Benzoin Condensation
  作者：Yajun Ma、Siping Wei、Jie Wu、Fei Yang、Bo Liu、Jingbo Lan、Shengyong Yang、Jingsong You

  DOI：10.1002/adsc.200800371

  日期：2008.11.3

  method for the enantioselective intermolecular benzoin condensation of aromatic aldehydes is described. The chiral bis-bicyclic triazolium salt – 1,3-bis(S)-5-benzyl-6,8-dihydro-5H-[1,4]oxazino[2,1-c][1,2,4]triazol-2-ium-2-yl}benzene dichloride [(S)-5a-1] is currently the most efficient precatalyst for the asymmetric variant of the benzoin condensation.

  描述了解决开发高效率的方法用于芳族醛的对映选择性分子间安息香缩合的长期挑战的解决方案。手性双-双环三唑鎓盐– 1,3-双（S）-5-苄基-6,8-二氢-5 H- [1,4]恶嗪[2,1- c ] [1,2,4 ]三唑-2-鎓-2-基}苯二氯化物[（S）-5a-1 ]目前是用于安息香缩合反应的不对称变体的最有效的预催化剂。