diexo-3-amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide | 109853-38-5

• 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: diexo-3-amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide
• 英文别名: rel-(1R,2R,3S,4S)-3-Amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide；(1S,2S,3R,4R)-3-amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide
• CAS: 109853-38-5
• 化学式: C₉H₁₄N₂O
• 分子量: 166.223
• InChiKey: PHLYRMHFDYEKDE-VGRMVHKJSA-N

物化性质

• 沸点：
  356.2±42.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  diexo-3-amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide 在 D(+)-10-樟脑磺酸 、 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 生成 (1S,2S,3R,4R)-3-((2-((3-(2-aminoacetamido)phenyl)amino)-5-chloropyrimidin-4-yl)amino)-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide
  参考文献：
  名称：

  Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases

  摘要：

  We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model.

  DOI：

  10.1021/jm5005144
• 作为产物：
  描述：

  ethyl 3-exo-aminobicyclo<2.2.1>hept-5-ene-2-exo-carboxylate 、 甲胺 以 甲醇 为溶剂， 反应 144.0h， 以82%的产率得到diexo-3-amino-N-methylbicyclo[2.2.1]hept-5-ene-2-carboxamide
  参考文献：
  名称：

  Stajer, Geza; Szabo, Angela E.; Bernath, Gabor, Journal of the Chemical Society. Perkin transactions I, 1987, p. 237 - 240

  摘要：

  DOI：

文献信息

• Continuous-Flow retro-Diels-Alder Reaction: A Process Window for Designing Heterocyclic Scaffolds
  作者：Imane Nekkaa、Márta Palkó、István M. Mándity、Ferenc Miklós、Ferenc Fülöp

  DOI：10.1002/ejoc.201800682

  日期：2018.8.31

  An approach based on a highly controlled continuous‐flow (CF) retro‐Diels–Alder reaction was developed for the synthesis of new compounds. Using this approach, we were able to rapidly screen reaction conditions to obtain the desired pyrimidinone moieties in short reaction times and high yields. We also present an alternative route for the synthesis of intermediates by CF cyclization.

  开发了一种基于高度受控的连续流（CF）Retro-Diels-Alder反应的方法来合成新化合物。使用这种方法，我们能够在短的反应时间和高收率下快速筛选反应条件以获得所需的嘧啶酮部分。我们还提出了一种通过CF环化合成中间体的替代途径。
• Retro-Diels-Alder Protocol for the Synthesis of Pyrrolo[1,2-<i>a</i>]pyrimidine and Pyrimido[2,1-<i>a</i>]isoindole Enantiomers
  作者：Ferenc Miklós、Zita Tóth、Mikko M. Hänninen、Reijo Sillanpää、Enikő Forró、Ferenc Fülöp

  DOI：10.1002/ejoc.201300452

  日期：2013.8

  4S)-3-aminonorbornene-2-carboxylic acid as a chiral auxiliary. The protocol is based on a domino ring-closure reaction, in which the relative configuration of the new asymmetric center is controlled by the stereochemistry of the amino acid, followed by a microwave-induced retro-Diels–Alder reaction.

  引入了一个简单的方案，通过使用 (-)-(1R,2R,3S,4S)-3-氨基降冰片烯-2-羧酸作为手性助剂来制备几种对映体纯杂环。该方案基于多米诺环闭合反应，其中新不对称中心的相对构型由氨基酸的立体化学控制，然后是微波诱导的逆狄尔斯-阿尔德反应。
• PYRIMIDINE INHIBITORS OF KINASES
  申请人：Curtin Michael

  公开号：US20100317680A1

  公开（公告）日：2010-12-16

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A 1 , A 2 , A 3 , A 4 , X and Y are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as aurora and KDR.

  本发明涉及式(I)的化合物或药用可接受的盐，其中A1、A2、A3、A4、X和Y在描述中有定义。本发明还涉及制备所述化合物的方法，以及含有所述化合物的组合物，用于抑制aurora和KDR等激酶。
• “Dry” and “Wet” Green Synthesis of 2,2′-Disubstituted Quinazolinones
  作者：Ferenc Miklós、Ferenc Fülöp

  DOI：10.1002/ejoc.200901052

  日期：2010.2

  (3), has been utilized to convert α- and β-aminocarboxamides 5a, 5b, 6a-c and 9 and cycloalkanones 2-2b and alkanones 2c-e into 1,4-diazaspiro-[4.5]decan-2-one (10) and cis-, diexo- or diendo-2,2'-disubstituted quinazolinones 5a, 5b, 7a-f and 8. diexo-Methylene-bridged carboxamides 6a and 6b were treated "on water" with N-benzylpiperidinone (11) to afford spiropiperidine-quinazolinones 12a and 12b. All

  在水性或无溶剂条件下非常方便、环境友好的螺环化反应，开发用于制备螺[环己烷-1,2'-(1'H)-喹唑啉]-4'(3'H)-one (3 )，已被用于将 α- 和 β-氨基甲酰胺 5a、5b、6a-c 和 9 以及环烷酮 2-2b 和烷酮 2c-e 转化为 1,4-二氮杂螺-[4.5]癸烷-2-one (10)和顺-、二外-或二烯-2,2'-二取代的喹唑啉酮5a、5b、7a-f和8。用N-苄基哌啶酮(11)“在水上”处理二外-亚甲基桥连的羧酰胺6a和6b，得到螺哌啶-喹唑啉酮 12a 和 12b。所有这些反应均在室温下进行，没有任何催化剂或助溶剂，产率高达 99%。
• Sterochemical Studies 107 Saturated heterocycles 111
  作者：Gábor Bernáth、Géza Stájer、Angela E. Szabó、Zsolt Szóke-Molnár、Pál Sohár、Gyula Argay、Alajos Kálmán

  DOI：10.1016/s0040-4020(01)81504-0

  日期：1987.1

  saturated methylene-bridged quinazoline-2,4-diones (7a-b) prepared from norbornane-diexo-β-amino acid (1) with isocyanates and PPA. When heated with PPA, compounds 9 can be isomerized to 7. For preparation of the unsaturated compounds 8, the amino acid 2 was converted into the acid amides (13) and cyclized with I,1'-carbonyl-diimidazole to tricyclic quinazoline-2,4-dione (8a-e), which decompose when

  由双异冰片降冰片烷和降冰片烯-氮杂环丁烷酮5和6与异氰酸芳基酯制备N-芳基氨基甲酰基取代的β-内酰胺（9和10）。与由降冰片烷-二exo-β-氨基酸（1）制得的饱和亚甲基桥连喹唑啉-2,4-二酮（7a-b）相比，该化合物的结构通过IR，NMR光谱和X射线分析得以阐明。与异氰酸酯和PPA。与PPA一起加热时，化合物9可以异构化为7。为制备不饱和化合物8，氨基酸2被转化为酰胺（13），并与I，1'-羰基-二咪唑环合成三环喹唑啉-2 ，4-二酮（8a-e），其在加热时分解，分解出环戊二烯以产生3-取代的尿嘧啶（14）。