N-苄基-4-哌啶酮-d4 | 88227-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: N-苄基-4-哌啶酮-d4
• 英文名称: 1-benzyl-4-piperidone-3,3,5,5-d₄
• 英文别名: 1-benzyl-3,3,5,5-tetradeuteriopiperidin-4-one；N-Benzyl-4-piperidone-d4
• CAS: 88227-09-2
• 化学式: C₁₂H₁₅NO
• 分子量: 193.225
• InChiKey: SJZKULRDWHPHGG-KXGHAPEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-苄基-4-哌啶酮-d4 在 lithium aluminium tetrahydride 、 potassium tert-butylate 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 25.0h， 生成 1-ethoxycarbonyl-1,2,5,6-tetrahydropyridine-3,5,5-d3
  参考文献：
  名称：

  Synthesis and dynamic NMR studies of the 3,7-diazabicyclo[4.1.0]heptane system

  摘要：

  AbstractA new bicyclic system, 3,7‐diazabicyclo[4.1.0]heptane, has been prepared from 3‐(ethoxycarbonyl)‐7,3‐oxazabicyclo[4.1.0]heptane by reaction with sodium azide and reduction of the resulting tosyloxy azide with lithium aluminum hydride. The molecule can exist in four stereoisomeric half‐chairs, depending on the configuration of the two nitrogen atoms. Half‐chair ring reversal and piperidine nitrogen inversion are fast on the NMR time scale at all observed temperatures. Inversion of the secondary aziridine nitrogen becomes slow as the temperature is lowered (Tc= −10°C). Complete analysis of the 1H spectrum was possible with the 1,5,5‐trideuteriated analog. At slow exchange, two aziridine invertomers are present with an exo/endo ratio of approximately 0.7 in toluene‐d8, 0.7 in CH2Cl2 and 1.7 in CHCl3/CH2Cl2. The free energy of activation for nitrogen inversion is 13.2 kcal mol−1 at −10°C in CHCl3/CH2Cl2.

  DOI：

  10.1002/omr.1270210904
• 作为产物：
  描述：

  N-苄基哌啶酮 在 sodium carbonate 、 sodium chloride 作用下， 以 重水 为溶剂， 反应 5.0h， 以94%的产率得到N-苄基-4-哌啶酮-d4
  参考文献：
  名称：

  Synthesis and dynamic NMR studies of the 3,7-diazabicyclo[4.1.0]heptane system

  摘要：

  AbstractA new bicyclic system, 3,7‐diazabicyclo[4.1.0]heptane, has been prepared from 3‐(ethoxycarbonyl)‐7,3‐oxazabicyclo[4.1.0]heptane by reaction with sodium azide and reduction of the resulting tosyloxy azide with lithium aluminum hydride. The molecule can exist in four stereoisomeric half‐chairs, depending on the configuration of the two nitrogen atoms. Half‐chair ring reversal and piperidine nitrogen inversion are fast on the NMR time scale at all observed temperatures. Inversion of the secondary aziridine nitrogen becomes slow as the temperature is lowered (Tc= −10°C). Complete analysis of the 1H spectrum was possible with the 1,5,5‐trideuteriated analog. At slow exchange, two aziridine invertomers are present with an exo/endo ratio of approximately 0.7 in toluene‐d8, 0.7 in CH2Cl2 and 1.7 in CHCl3/CH2Cl2. The free energy of activation for nitrogen inversion is 13.2 kcal mol−1 at −10°C in CHCl3/CH2Cl2.

  DOI：

  10.1002/omr.1270210904

文献信息

• A concise synthesis of 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4- b ]pyridin-5(7 H )-ones], 3-aryl-, and alkylphthalides
  作者：Jeffrey T. Kuethe、Kevin M. Maloney

  DOI：10.1016/j.tet.2013.02.051

  日期：2013.6

  A synthetically useful protocol has been developed for the preparation of highly functionalized 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4-b]pyridin-5(7H)-ones], 3-aryl-, and alkylphthalides. Reaction of 2-iodobenzoate esters and 2-iodopyridine carboxylate esters with i-PrMgCl center dot LiCl in the presence of cyclic ketones under standard Barbier reaction conditions affords 3,4-fused spiro[isobenzofuran-3-ones] and spiro[furo[3,4-b]pyridin-5(7H)-ones] in good to excellent yields. Step-wise addition of i-PrMgCl center dot LiCl to 2-iodobenzoate esters followed by trapping with various aldehydes yields 3-aryl and 3-alkylphthalides; whereas, under similar conditions access to 3-aryl and 3-alylazaphthalides is also possible. Extension of this methodology toward the preparation of 3-n-butylphthalide and chrycolide, a natural product isolated from the leaves and stems of Chrysanthemum coronarium, is also described. (C) 2013 Elsevier Ltd. All rights reserved.
• DEUTERIUM-ENRICHED LAPAQUISTAT
  申请人：Czarnik Anthony W.

  公开号：US20090088416A1

  公开（公告）日：2009-04-02

  The present application describes deuterium-enriched lapaquistat, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
• MORPHIC FORMS OF A MUTANT BRAF DEGRADER AND METHODS OF MANUFACTURE THEREOF
  申请人：[en]C4 THERAPEUTICS, INC.

  公开号：WO2024119111A2

  公开（公告）日：2024-06-06

  Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3- [[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[l-[3-(2,4- di oxo-1, 3-diazinan-l -yl)-5-fluoro-1 -methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa- 8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.