(4S)-2-[(4-methoxyphenyl)methyl]-4-methyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione | 204513-00-8

• 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-methoxyphenyl)methyl]-4-methyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione
• CAS: 204513-00-8
• 化学式: C₂₀H₁₉N₃O₃
• 分子量: 349.389
• InChiKey: NFQLITHRIQRBBU-ZDUSSCGKSA-N

物化性质

• 沸点：
  591.2±60.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-2-[(4-methoxyphenyl)methyl]-4-methyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione 在 lithium aluminium tetrahydride 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 反应 1.6h， 生成 (1S,4S)-1-Hydroxy-2-(4-methoxy-benzyl)-4-methyl-1,2-dihydro-2,4a,9-triaza-anthracene-3,10-dione
  参考文献：
  名称：

  Stereochemical course of acylation and aldol condensation in (4S)-4-methyl-2-benzyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones

  摘要：

  Acylation of 1 leads to the syn derivatives 2. Traces of the anti isomers equilibrate to the syn isomers when stored in CHCl3. Aldol condensation showed great diastereoselectivity, but racemization could not be avoided. The configuration of the new introduced stereogenic centres has been assigned on the basis of H-1-NMR data and NOE measurements. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(97)00614-9
• 作为产物：
  描述：

  ethyl 2-[(4-methoxyphenyl)methyl-[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetate 在 palladium on activated charcoal 氢气 、 triethyloxonium fluoroborate 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 25.0~140.0 ℃ 、241.32 kPa 条件下， 反应 28.5h， 生成 (4S)-2-[(4-methoxyphenyl)methyl]-4-methyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione
  参考文献：
  名称：

  Stereochemical course of acylation and aldol condensation in (4S)-4-methyl-2-benzyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones

  摘要：

  Acylation of 1 leads to the syn derivatives 2. Traces of the anti isomers equilibrate to the syn isomers when stored in CHCl3. Aldol condensation showed great diastereoselectivity, but racemization could not be avoided. The configuration of the new introduced stereogenic centres has been assigned on the basis of H-1-NMR data and NOE measurements. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(97)00614-9

文献信息

• 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。
• Intramolecular Friedel−Crafts-Type Reactions Involving <i>N</i>-Acyliminium Ions Derived from Glycine Templates
  作者：Juan Domingo Sánchez、María Teresa Ramos、Carmen Avendaño

  DOI：10.1021/jo010166y

  日期：2001.8.1

  Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones (1b-m) in which the alkyl chain is (CH(2))(n), n = 1-3, behave as glycine templates giving by treatment with [hydroxy(tosyloxy)iodo]benzene in ethyl acetate cis-1-tosyloxy derivatives. When these compounds contain electron-rich aryl substituents with n = 2, they spontaneously cyclize through intramolecular

  对映体纯的4-取代的2-芳烷基-2,4-二氢-1H-吡嗪并[2,1-b]喹唑啉-3,6-二酮（1b-m），其中烷基链为（CH（2））（ n），n = 1-3，表现为甘氨酸模板，通过在乙酸乙酯的cis-1-tosyloxy衍生物中用[羟基（tosyloxy）碘]苯处理得到。当这些化合物包含n = 2的富电子芳基取代基时，它们通过分子内Friedel-Crafts型非对映选择性反应自发环化，生成五环或六环化合物。否则，它们通过溶剂分解得到顺式-1-烷氧基衍生物，如果n = 2、3，则可以在第二步中在酸中环化。所有这些反应必须通过类似于S（N）1机理的N-酰氨基发生。 。1-烷氧基-2-芳基甲基衍生物不愿环化，使反式-1-羟基化合物成为唯一的分离反应产物。
• 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。
• Vilsmeier and Mannich reactions on (4S)-N2-substituted 4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones
  作者：María Fernandez、María L. Heredia、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/s0040-4020(98)83013-5

  日期：1998.3

  The enamine character of the CH2-C(11a)=N(11) fragment in the title compounds was studied. Compounds 1 gave 1-dimethylaminomethylene products 5 after Vilsmeier reaction. The l-formyl derivatives, obtained by alkaline hydrolysis of 5, were isolated as enol tautomers and were very unstable in acid media. On the other hand, acid-promoted elimination of dimethylamine from the Mannich reaction products 7 gave I-methylene derivatives 8, which showed an interesting reactivity. Thus, 8a dimerized in acid to the ethylidene derivative 9a. 1,4-Dialkyl-compounds 7 and 9a showed a 1,4-syn-stereochemistry. (C) 1998 Elsevier Science Ltd. All rights reserved.
• New findings in the alkylation and N-deprotection of (4S)-4-methyl-2-benzyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones
  作者：Félix L. Buenadicha、M.Teresa Bartolomé、M.Jesús Aguirre、Carmen Avendaño、Mónica Söllhuber

  DOI：10.1016/s0957-4166(97)00629-0

  日期：1998.2

  Alkyl halides behave differently to benzyl halides in C-1 alkylation of the title compounds. The syn and anti 1,4-disubstituted diastereomers thus obtained show different regioselectivity by further alkylation leading to the 1,4,4- and 1,1,4-trisubstituted compounds, respectively. Alkylation is always directed anti with respect to the bulkier substituent at C-1 or C-4. Debenzylation attempts on 2-benzyl-derivatives 1b by treatment with HCOOH and C/Pd or H-2/C-Pd/MeOH/H+ led to C-1 oxidised or 7,8,9,10-tetrahydro-derivatives. Deprotection of 2-p-methoxybenzyl- and 2-(2,4-dimethoxybenzyl)-derivatives with CAN and with TFA/anisole, respectively, was successful, but in the latter case epimerization at C-1 occurred. (C) 1998 Elsevier Science Ltd. All rights reserved.