tert-butyl (2S,5S)-2-[(dimethylamino)carbonyl]-5-methylpyrrolidine-1-carboxylate | 1033714-10-1

• 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: tert-butyl (2S,5S)-2-[(dimethylamino)carbonyl]-5-methylpyrrolidine-1-carboxylate
• 英文别名: (2S,5R)-tert-butyl 2-(dimethylcarbamoyl)-5-methylpyrrolidine-1-carboxylate；tert-butyl (2S,5S)-2-(dimethylcarbamoyl)-5-methylpyrrolidine-1-carboxylate
• CAS: 1033714-10-1
• 化学式: C₁₃H₂₄N₂O₃
• 分子量: 256.345
• InChiKey: AROMNPJDEVWADS-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,5S)-2-[(dimethylamino)carbonyl]-5-methylpyrrolidine-1-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以98%的产率得到(2S,5S)-2-(dimethylaminomethyl)-1,5-dimethylpyrrolidine
  参考文献：
  名称：

  Flexible and Modular Syntheses of Enantiopure 5-cis-Substituted Prolinamines from l-Pyroglutamic Acid

  摘要：

  A wide range (25 examples) of 5-cis-substituted prolinamines is prepared in five to ten steps starting from cheap L-pyroglutamic acid. Three routes, differing mainly in the order of introduction of the substituents at the 5-cis position, the pyrrolidine nitrogen atom, and the exocyclic amino function, are successfully developed.

  DOI：

  10.1055/s-0034-1379457
• 作为产物：
  描述：

  L-焦谷氨酸 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 三甲基乙酰氯 、 三乙酰氧基硼氢化钠 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 52.17h， 生成 tert-butyl (2S,5S)-2-[(dimethylamino)carbonyl]-5-methylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Flexible and Modular Syntheses of Enantiopure 5-cis-Substituted Prolinamines from l-Pyroglutamic Acid

  摘要：

  A wide range (25 examples) of 5-cis-substituted prolinamines is prepared in five to ten steps starting from cheap L-pyroglutamic acid. Three routes, differing mainly in the order of introduction of the substituents at the 5-cis position, the pyrrolidine nitrogen atom, and the exocyclic amino function, are successfully developed.

  DOI：

  10.1055/s-0034-1379457

文献信息

• Imidazothiazole derivatives
  申请人：Kawato Haruko

  公开号：US20090312310A1

  公开（公告）日：2009-12-17

  There is provided a novel compound that inhibits interaction between murine double minute 2 (Mdm2) protein and p53 protein and exhibits anti-tumor activity. The present invention provides an imidazothiazole derivative represented by the following formula (1) having various substituents that inhibits interaction between Mdm2 protein and p53 protein and exhibits anti-tumor activity: wherein R 1 , R 2 , R 3 , R 4 , and R 5 in the formula (1) each has the same meaning as defined in the specification.

  提供了一种新的化合物，它抑制小鼠双分子分钟2（Mdm2）蛋白与p53蛋白之间的相互作用，并展现出抗肿瘤活性。本发明提供了一种咪唑噻唑衍生物，其表示为以下公式（1），具有各种取代基，可抑制Mdm2蛋白与p53蛋白之间的相互作用并展现出抗肿瘤活性：其中，公式（1）中的R1、R2、R3、R4和R5每个都具有规范中定义的相同含义。
• Synthesis and evaluation of novel orally active p53–MDM2 interaction inhibitors
  作者：Masaki Miyazaki、Hiroyuki Naito、Yuuichi Sugimoto、Keisuke Yoshida、Haruko Kawato、Tooru Okayama、Hironari Shimizu、Masaya Miyazaki、Mayumi Kitagawa、Takahiko Seki、Setsuko Fukutake、Yoshinobu Shiose、Masashi Aonuma、Tsunehiko Soga

  DOI：10.1016/j.bmc.2013.04.056

  日期：2013.7

  We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53. (C) 2013 Elsevier Ltd. All rights reserved.
• Flexible and Modular Syntheses of Enantiopure 5-cis-Substituted Prolinamines from l-Pyroglutamic Acid
  作者：Matthias Breuning、Felix Prause、Johannes Kaldun、Benjamin Arensmeyer、Benedikt Wennemann、Benjamin Fröhlich、Dagmar Scharnagel

  DOI：10.1055/s-0034-1379457

  日期：——

  A wide range (25 examples) of 5-cis-substituted prolinamines is prepared in five to ten steps starting from cheap L-pyroglutamic acid. Three routes, differing mainly in the order of introduction of the substituents at the 5-cis position, the pyrrolidine nitrogen atom, and the exocyclic amino function, are successfully developed.