5-(2-phenyl-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester | 216962-29-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2-phenyl-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester
• 英文别名: Ethyl 4-acetyl-5-(2-phenylethyl)-1,2-oxazole-3-carboxylate
• CAS: 216962-29-7
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: NDJWGAXMWOFCAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2-phenyl-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester 在 四(三苯基膦)钯 盐酸 、 1,3-二甲基巴比妥酸 、 dimethyl sulfide borane 、 三氟化硼乙醚 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 60.19h， 生成 (S)-5-(2-phenyl-ethyl)-4-(2-amino-2-methoxycarbonyl-ethyl)-3-isoxazolecarboxylic acid ethyl ester
  参考文献：
  名称：

  Catalytic Asymmetric Synthesis of Glutamate Analogues

  摘要：

  Utilizing our lateral metalation coupled with Jacobsen's catalytic asymmetric amino nitrile synthesis, we have demonstrated the ability to synthesize isoxazole-containing amino acid glutamate analogues in high yield and high enantiomeric excesses. Chiral centers alpha or beta at the C-5 position do not detract from diastereoselectivity of the Jacobsen-Strecker reaction.

  DOI：

  10.1021/ol049619m
• 作为产物：
  描述：

  3-isoxazolecarboxylic acid 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 在 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 丙酮 为溶剂， 生成 5-(2-phenyl-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester
  参考文献：
  名称：

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate with 5,5-dimethyl-1,3-dioxanyl as a directing group

  摘要：

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate, a functionalized isoxazole AMPA analog, occurs cleanly at the C-5 methyl group with 5,5-dimethyl-1,3-dioxanyl as a directing group. The 4-acetyl isoxazole derivatives were transformed selectively by a modified Willgerodt-Kindler reaction into the corresponding homologated methyl esters after deprotection. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01782-1

文献信息

• The Lateral Metalation of Isoxazolo[3,4-d]pyridazinones towards Hit-to-Lead Development of Selective Positive Modulators of Metabotropic Glutamate Receptors
  作者：Christina A. Gates、Donald S. Backos、Philip Reigan、Nicholas R. Natale

  DOI：10.3390/molecules28196800

  日期：——

  Isoxazolo[3,4-d] pyridazinones ([3,4-d]s) were previously shown to have selective positive modulation at the metabotropic glutamate receptor (mGluR) Subtypes 2 and 4, with no functional cross-reactivity at mGluR1a, mGluR5, or mGluR8. Additional analogs were prepared to access more of the allosteric pocket and achieve higher binding affinity, as suggested by homology modeling. Two different sets of

  异恶唑并[3,4-d]哒嗪酮 ([3,4-d]s) 先前已被证明对代谢型谷氨酸受体 (mGluR) 亚型 2 和 4 具有选择性正向调节作用，而与 mGluR1a、mGluR5 没有功能性交叉反应，或 mGluR8。正如同源模型所表明的，制备了额外的类似物以进入更多的变构口袋并实现更高的结合亲和力。生成了两组不同的类似物。一种使用完全形成的[3,4-d]和带有或不带有卤素的N6-芳基。它们在异恶唑的 C3 处成功进行了选择性横向金属化和亲电猝灭 (LM&EQ)。在第二组类似物中，通过 4-苯乙酰基-3-乙氧羰基-5-甲基异恶唑与相应的肼缩合，在 [3,4-d] 环的 C4 位引入苯基，生成 3 ,4-ds 2b 和 2j 至 2n。
• Catalytic Asymmetric Synthesis of Glutamate Analogues
  作者：David J. Burkhart、Andrew R. McKenzie、Jared K. Nelson、Katherine I. Myers、Xue Zhao、Kathy R. Magnusson、Nicholas R. Natale

  DOI：10.1021/ol049619m

  日期：2004.4.1

  Utilizing our lateral metalation coupled with Jacobsen's catalytic asymmetric amino nitrile synthesis, we have demonstrated the ability to synthesize isoxazole-containing amino acid glutamate analogues in high yield and high enantiomeric excesses. Chiral centers alpha or beta at the C-5 position do not detract from diastereoselectivity of the Jacobsen-Strecker reaction.
• Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate with 5,5-dimethyl-1,3-dioxanyl as a directing group
  作者：Peiwen Zhou、N.R. Natale

  DOI：10.1016/s0040-4039(98)01782-1

  日期：1998.11

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate, a functionalized isoxazole AMPA analog, occurs cleanly at the C-5 methyl group with 5,5-dimethyl-1,3-dioxanyl as a directing group. The 4-acetyl isoxazole derivatives were transformed selectively by a modified Willgerodt-Kindler reaction into the corresponding homologated methyl esters after deprotection. (C) 1998 Elsevier Science Ltd. All rights reserved.