(S)-4-benzyl-3-(3-ethylpentanoyl)oxazolidin-2-one | 544437-60-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (S)-4-benzyl-3-(3-ethylpentanoyl)oxazolidin-2-one
• 英文别名: (4S)-4-benzyl-3-(3-ethylpentanoyl)-1,3-oxazolidin-2-one
• CAS: 544437-60-7
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: RNZSRHCHCDNYGC-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-4-benzyl-3-(3-ethylpentanoyl)oxazolidin-2-one 在 双(三甲基硅烷基)氨基钾 、 2,4,6-三异丙基苯磺酰叠氮化物 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.88h， 以56%的产率得到(2S),(4S)-3-(2-azido-3-ethyl-1-oxopentyl)-4-(phenylmethyl)-2-oxazolidinone
  参考文献：
  名称：

  Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

  摘要：

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm801252w
• 作为产物：
  描述：

  、 (S)-4-苄基-2-唑烷酮 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以123.7 g的产率得到(S)-4-benzyl-3-(3-ethylpentanoyl)oxazolidin-2-one
  参考文献：
  名称：

  Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

  摘要：

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm801252w

文献信息

• Process for the synthesis of chirally pure beta-amino-alcohols
  申请人：Wyeth

  公开号：US20030144531A1

  公开（公告）日：2003-07-31

  A process is provided for preparing chirally pure S-enantiomers of &agr;-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R) 2 CH(CH 2 ) n CH 2 X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an &agr;-azido acid; h) reducing the &agr;-azido acid to the &agr;-amino acid; and i) recrystallizing the &agr;-amino acid to the chirally pure &agr;-amino acid. A process is also provided for preparing chirally pure S-enantiomers of &bgr;-amino alcohols further comprising the steps of reducing the crude &agr;-amino acid to the &bgr;-amino alcohol and recrystallizing the &bgr;-amino alcohol to the chirally pure &bgr;-amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl &bgr;-amino alcohols further comprising the steps of sulfonylating the &bgr;-amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl &bgr;-amino alcohols.

  提供了一种制备手性纯S-对映体α-氨基酸的过程，包括以下步骤：a) 从具有化学式(R)2CH(CH2)n X的烷基卤化物制备有机金属试剂；b) 将有机金属试剂加入二氧化碳以得到羧酸；c) 在三级胺碱存在下，用酸氯化物、三氯化磷、酸酐或氯化硫酰氯激活羧酸；d) 将步骤c)的产物与S-4-苄基-2-噁唑烷酮的碱金属盐反应；e) 用强非亲核碱处理步骤d)的产物以形成烯醇负离子；f) 用2,4,6-三异丙基苯磺酰氮化物捕获烯醇负离子以得到噁唑烷酮氮化物；g) 用水性碱水解噁唑烷酮氮化物以得到α-叠氮酸；h) 还原α-叠氮酸以得到α-氨基酸；i) 对α-氨基酸进行再结晶以得到手性纯α-氨基酸。还提供了一种制备手性纯S-对映体β-氨基醇的过程，进一步包括将粗α-氨基酸还原为β-氨基醇，并对β-氨基醇进行再结晶以得到手性纯β-氨基醇。还提供了一种制备手性纯S-对映体N-磺酰基β-氨基醇的过程，进一步包括用5-氯硫代苯磺酰卤化物对β-氨基醇进行磺酰化；并进行再结晶以得到手性纯N-磺酰基β-氨基醇。
• US6800764B2
  申请人：——

  公开号：US6800764B2

  公开（公告）日：2004-10-05