2(S)-azido-3-ethylpentanoic acid | 544437-62-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2(S)-azido-3-ethylpentanoic acid
• 英文别名: (2S)-2-azido-3-ethylpentanoic acid
• CAS: 544437-62-9
• 化学式: C₇H₁₃N₃O₂
• 分子量: 171.199
• InChiKey: BLZHYNVSEYMXME-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  51.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2(S)-azido-3-ethylpentanoic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 20.0h， 以79%的产率得到(S)-2-氨基-3-乙基戊酸
  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：

  (2S),(4S)-3-(2-azido-3-ethyl-1-oxopentyl)-4-(phenylmethyl)-2-oxazolidinone 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以77%的产率得到2(S)-azido-3-ethylpentanoic acid
  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)nCH2X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。
• PROCESS FOR THE SYNTHESIS OF CHIRALLY PURE b-AMINO-ALCOHOLS
  申请人：Wyeth

  公开号：EP1461303A2

  公开（公告）日：2004-09-29
• US6800764B2
  申请人：——

  公开号：US6800764B2

  公开（公告）日：2004-10-05
• [EN] PROCESS FOR THE SYNTHESIS OF CHIRALLY PURE beta -AMINO-ALCOHOLS<br/>[FR] PROCEDE DE SYNTHESE DE DOLLAR G(B)-AMINO-ALCOOLS A PURETE CHIRALE
  申请人：WYETH CORP

  公开号：WO2003050063A2

  公开（公告）日：2003-06-19

  A process is provided for preparing chirally pure S-enantiomers of α-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the Formula (R)2CH(CH2)nCH2X; 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 α-azido acid; h) reducing the α-azido acid to the α-amino acid; and i) recrystallizing the α-amino acid to the chirally pure α-amino acid. A process is also provided for preparing chirally pure S-enantiomers of β-amino alcohols further comprising the steps of reducing the crude α-amino acid to the β-amino alcohol and recrystallizing the β-amino alcohol to the chirally pure β-amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl β-amino alcohols further comprising the steps of sulfonylating the β-amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl β-amino alcohols.
• Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease
  作者：Scott C. Mayer、Anthony F. Kreft、Boyd Harrison、Magid Abou-Gharbia、Madelene Antane、Suzan Aschmies、Kevin Atchison、Michael Chlenov、Derek C. Cole、Thomas Comery、George Diamantidis、John Ellingboe、Kristi Fan、Rocco Galante、Cathleen Gonzales、Douglas M. Ho、Molly E. Hoke、Yun Hu、Donna Huryn、Uday Jain、Mei Jin、Kenneth Kremer、Dennis Kubrak、Melissa Lin、Peimin Lu、Ron Magolda、Robert Martone、William Moore、Aram Oganesian、Menelas N. Pangalos、Alex Porte、Peter Reinhart、Lynn Resnick、David R. Riddell、June Sonnenberg-Reines、Joseph R. Stock、Shaiu-Ching Sun、Erik Wagner、Ting Wang、Kevin Woller、Zheng Xu、Margaret M. Zaleska、Joseph Zeldis、Minsheng Zhang、Hua Zhou、J. Steven Jacobsen

  DOI：10.1021/jm801252w

  日期：2008.12.11

  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.