(4S)-2,4-dimethyl-2,4-dihydro-(1H)-pyrazino<2,1-b>quinazoline-3,6-dione | 54799-50-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (4S)-2,4-dimethyl-2,4-dihydro-(1H)-pyrazino<2,1-b>quinazoline-3,6-dione
• 英文别名: (4S)-2,4-dimethyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione；(4S)-2,4-dimethyl-2H-pyrazino[2,1-b]quinazoline-3,6(1H,4H)-dione；(4S)-2,4-dihydro-2,4-dimethyl-1H-pyrazino[2,1-b]quinazoline-3,6-dione；2,4-dimethyl-1,2-dihydro-pyrazino[2,1-b]quinazoline-3,6-dione；(4S)-2,4-dimethyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione
• CAS: 54799-50-7
• 化学式: C₁₃H₁₃N₃O₂
• 分子量: 243.265
• InChiKey: ILTHWCCSAFNRFY-QMMMGPOBSA-N

物化性质

• 沸点：
  461.7±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-2,4-dimethyl-2,4-dihydro-(1H)-pyrazino<2,1-b>quinazoline-3,6-dione 在 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (-)-(1R,4S)-1-hydroxy-2,4-dimethyl-1-phenyl-2,4-dihydro-(1H)-pyrazino[2,1-b]quinazoline-3,6-dione
  参考文献：
  名称：

  Cyclisation of (4S)-4-methyl-2-phenethyl-2,4-dihydro-(1H)-pyrazino[2,1-b]quinazoline-3,6-dione derivatives via N-acyliminium ions

  摘要：

  Enantiomerically pure 1-methylene and 1-oxo derivatives (compounds 4 and 10, respectively) of compounds 1 were obtained and studied as precursors of N-acyliminium ions. 1-Substituted-1-hydroxyderivatives, obtained by regioselective syn-addition of organometallics to compounds 10 gave the desired species under acid treatment while compounds 4 did not. -Phenethyl substituted N-acyliminium ions gave isoquino[1',2':3,4]pyrazino[2, l-b]quinazoline-8,11-diones through a Pictet-Spengler-type cyclisation. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00492-x
• 作为产物：
  描述：

  (6S)-1-(2-azidobenzoyl)-4,6-dimethylpiperazine-2,5-dione 在 三丁基膦 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以71%的产率得到(4S)-2,4-dimethyl-2,4-dihydro-(1H)-pyrazino<2,1-b>quinazoline-3,6-dione
  参考文献：
  名称：

  Cledera, Pilar; Villacampa, Mercedes; Avendano, Carmen, ARKIVOC, 2011, vol. 2011, # 3, p. 72 - 98

  摘要：

  DOI：

文献信息

• Microwave-Assisted, Solvent-Free Synthesis of Several Quinazoline Alkaloid Frameworks
  作者：J. Menéndez、Pilar Cledera、Juan Sánchez、Esmeralda Caballero、Tamara Yates、Elena Ramírez、Carmen Avendaño、M. Ramos

  DOI：10.1055/s-2007-990818

  日期：2007.11

  Microwave irradiation leads to a considerable improvement of the cyclocondensation between anthranilic acid and lactim ethers derived from piperazine-2,5-diones in terms of reaction times, yields, and stereocenter integrity. This reaction has been used to prepare some derivatives of the pyrazino[2,1-b]quinazoline-3,6-dione system present in many quinazoline alkaloids. It could also be applied to the synthesis of compounds containing the complete hexacyclic ring system of the anti-MDR natural product N-acetyl­ardeemin, and other comprising the pentacyclic framework of circumdatin E. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino[2,1-b:5,4-b′]diquinazoline-8,16-dione in excellent yield.

  微波辐照显著改善了邻氨基苯甲酸与来自哌嗪-2,5-二酮的乳酰亚胺醚之间的环加成反应，在反应时间、产率和立体中心完整性方面均有显著提升。该反应已被用于制备多种喹唑啉生物碱中存在的吡嗪并[2,1-b]喹唑啉-3,6-二酮系统的衍生物。它还可以应用于合成含有抗多药耐药天然产物N-乙酰基阿德米宁的完整六环体系化合物，以及其他包含circumdatin E的五环框架的化合物。微波辅助反应在应用于双乳酰亚胺醚时也比热反应更为高效，得到了对应的五环吡嗪并[2,1-b:5,4-b′]双喹唑啉-8,16-二酮，产率极佳。
• Nucleophilic additions to (4 S )-1-alkylidene-2,4-dihydro-1 H -pyrazino[2,1- b ]quinazoline-3,6-diones
  作者：Marı́a Luisa Heredia、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/s0040-4020(01)00046-1

  日期：2001.3

  reactivity against amines or Grignard reagents under copper(I) catalysis, but efficient additions to the exocyclic double bond took place with mercaptides or stabilized carbanions. Regio- and diastereoselective addition of organometallic reagents occurred at the C(3)-position and, in 1-methylene derivatives, these reactions were followed by a rearrangement of the intermediate oxy-anion to give pyrido[2,1-b]quinazolines

  标题化合物为双氢氨基酸模板的研究表明，它们在铜（I）催化下对胺或格氏试剂缺乏反应性，但硫醇盐或稳定的碳负离子有效地加到了环外双键上。在C（3）-位发生有机金属试剂的区域和非对映选择性加成，在1-亚甲基衍生物中，这些反应之后是中间氧阴离子的重排，从而得到吡啶并[2,1- b ]喹唑啉。
• Diastereoselective Reactions in Glycine Templates Containing an <i>ent</i>-Ardeemin Fragment
  作者：Sonsoles Martín-Santamaría、Raúl Corzo-Suárez、Carmen Avendaño、Modesta Espada、Federico Gago、Santiago García-Granda、Henry S. Rzepa

  DOI：10.1021/jo015713u

  日期：2002.4.1

  1-b]quinazoline-3,6-dione (1) at C(1) with electrophiles and nucleophiles, respectively. The found anti/syn ratio of compound 8, which is a seco-ent-ardeemin analogue obtained by alkylation of 1 with gramine methiodide, confirms this computational model. A close similarity between the calculated geometry of the piperazine ring in the anti isomers of 1,2,4-trialkyl derivatives and that deduced from their (1)H

  从SCF-MO计算得出的自洽反应场溶剂化模型显示出在建模源自（4S）-2,4-二甲基-2,4-二氢-1H-的阴离子和阳离子反应的非对映选择性方面是可靠的吡嗪并[2,1-b]喹唑啉-3,6-二酮（1）在C（1）分别具有亲电子试剂和亲核试剂。所发现的化合物8的抗/ syn比率证实了该计算模型，该化合物是通过将1与麦氨酰胺甲硫醇烷基化而获得的一种前体-ardeemin类似物。还确定了在1,2,4-三烷基衍生物的反异构体中哌嗪环的计算几何形状与从其（1）H NMR（溶液）和X射线数据推导的结果之间存在相似性。
• Solvent-Free Cyclocondensation of Lactim Ethers with Anthranilic Acid under Microwave Irradiation
  作者：J. Carlos Menéndez、Pilar Cledera、J. Domingo Sánchez、Esmeralda Caballero、Carmen Avendaño、M. Teresa Ramos

  DOI：10.1055/s-2004-817784

  日期：——

  Microwave irradiation greatly improves the results of the cyclocondensation between anthranilic acid and lactim ethers derived from 2,5-piperazinediones in terms of reaction times, yields and stereocenter integrity, leading to pyrazino[2,1-b]quinazoline-3,6-diones. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino [2,1-b:5,4-b′]diquinazol­ine-5,13-dione in excellent yield, and it also improved the preparation of compounds containing the ring system of the anti-MDR natural product N-acetylardeemin.

  微波辐射极大地改善了邻氨基苯甲酸与2,5-哌嗪二酮衍生的内酰亚胺之间的环缩合反应时​​间、产率和立构中心完整性，从而生成吡嗪并[2,1-b]喹唑啉-3,6-二酮。当应用于双内酰亚胺醚时，微波辅助反应也比热反应好得多，导致在优良的收率，同时也改进了抗MDR天然产物N-乙酰葆明含环体系​​化合物的制备。
• 1-Bromo-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones as α-bromoglycine templates
  作者：Marı́a Luisa Heredia、Marı́a Fernández、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/s0957-4166(01)00067-2

  日期：2001.3

  The title compounds behaved as α-bromoglycine templates. Radical substitutions and SN1-type nucleophilic additions proceeded with retention of stereochemistry, while SN2-type displacements occurred with net inversion of configuration. A homocoupling product was obtained in attempting a Stille cross-coupling reaction.

  标题化合物表现为α-溴甘氨酸模板。自由基取代和S N 1型亲核加成继续保留立体化学，而S N 2型置换发生净构型倒置。在尝试进行Stille交叉偶联反应时获得了均偶联产物。