(4S)-4-methyl-1,2,3,4-tetrahydro-5H-pyrazino[2,1-b]quinazoline-3,6-dione | 204770-99-0

• 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)-4-methyl-1,2,3,4-tetrahydro-5H-pyrazino[2,1-b]quinazoline-3,6-dione
• 英文别名: (4S)-4-methyl-2,3,4,6-tetrahydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione；(4S)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione；(4S)-4-methyl-1H-pyrazino[2,1-b]quinazoline-3,6-dione
• CAS: 204770-99-0
• 化学式: C₁₂H₁₁N₃O₂
• 分子量: 229.238
• InChiKey: HNBURSUZZIHKGV-ZETCQYMHSA-N

物化性质

• 熔点：
  196-197 °C
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-4-methyl-1,2,3,4-tetrahydro-5H-pyrazino[2,1-b]quinazoline-3,6-dione 在 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 (+)-(5aR,8S,15bR,16aR)-8-methyl-5,5a,8,15b,16,16a-hexahydro-indolo[3'',2''-4',5']pyrrolo[2',1'-3,4]pyrazino[2,1-b]quinazoline-7,10-dione
  参考文献：
  名称：

  Influence of N(2)-substitution in the alkylation of (4S)-alkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones

  摘要：

  1-Alkylation of O(3)-lactim, N(11)-azaenolate dilithium species derived from N(2)-H compounds 1a and 1b and the lithium azaenolates derived from the N(2)-phenyl and N(2)-(1-arylethyl) substituted compounds 2, 3 and 4 is studied. In 1 the trans-diastereoselectivity of 1-alkylation is controlled by 1,4-asyrnmetric induction, with some of these products prect.rsors of the ent-ardeemin framework. By contrast in compounds 2-4, the stabilization of the lithium azaenolate imposed by the phenyl substituent in 2, and the repulsive steric 1,2- interactions present in the initially formed 1,4-trans derivatives of 3 and 4, favou a C(1)-epimerization to the 1,4-cis isomers. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.07.034
• 作为产物：
  描述：

  ethyl N-(benzyloxycarbonyl)-L-alanylglycinate 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 三丁基膦 、 氢气 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 46.0h， 生成 (4S)-4-methyl-1,2,3,4-tetrahydro-5H-pyrazino[2,1-b]quinazoline-3,6-dione
  参考文献：
  名称：

  A New Route toward 4-Substituted Pyrazino[2,1-b]quinazoline-3,6-dione Systems. Total Synthesis of Glyantrypine

  摘要：

  Treatment of sodium N-(o-azidobenzoyl)aminoacylglycinates 8 with acetic anhydride afforded 1-acetyl-4-(o-azidobenzoyl)-2,5-piperazinediones 7, with complete retention of the stereochemistry. The intramolecular aza Wittig reactions of compounds 7 in the presence of tributylphosphine followed by deacetylation gave 1,2-unsubstituted pyrazino[2,1-b]quinazoline-3,6-diones 1. This route was adapted to the synthesis of both enantiomers of the alkaloid glyantrypine.

  DOI：

  10.1021/jo991626e

文献信息

• 10.1039/d4ob00529e
  作者：Zhang, Yuanmu、Zhu, Lingxuan、Lu, Yi、Lei, Xinsheng、Li, Yingxia

  DOI：10.1039/d4ob00529e

  日期：——

  skeletons occupy a prominent position in drug discovery. Even with currently available methods there still remain unmet needs for flexible access to such structures. Herein, we have explored a mild “one pot” procedure for the construction of various quinazolinone-[2,3]-fused polycycles. The procedure involves Pd-catalyzed carbonylation of N-(2-iodophenyl)acetamides, release of the masked terminal amine

  多种喹唑啉酮-[2,3]-稠合多环骨架在药物发现中占据着重要地位。即使采用当前可用的方法，对于灵活访问此类结构的需求仍然未得到满足。在此，我们探索了一种温和的“一锅法”程序来构建各种喹唑啉酮-[2,3]-稠合多环。该过程包括 Pd 催化的N- (2-碘苯基)乙酰胺的羰基化、掩蔽末端胺的释放以及两个连续的自发环化。这种普遍适用的方法具有从容易获得的起始材料中轻松组装前体、反应条件温和、操作不繁琐和多环多样性的特点。
• A new stereocontrolled approach to fused polycyclic compounds containing a diketopiperazine ring
  作者：Fernando Hernández、Carmen Avendaño、Mónica Söllhuber

  DOI：10.1016/j.tetasy.2005.08.034

  日期：2005.10

  Representative (1S)- and (4S)-alkyl-1,4-dihydropyrazino[2,1-b]quinazoline-3,6-dione lactim ethers were regio- and diastereoselectively alkylated after metallation to give the corresponding 1,4-trans-isomers with retention of the stereocentres. The results were compared with the previously studied lactams. The (1R,4S)-dialkyl derivatives obtained by C(1)-alkyation with bifunctional reagents were lately cyclized to complex polycyclic compounds through a second N(2)-alkylation promoted by sodium iodide. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis of a Seco Analogue of Ardeemin
  作者：Carmen Avendaño、Esmeralda Caballero、J. Carlos Menéndez

  DOI：10.3987/com-00-8942

  日期：——
• 1-Alkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones as glycine templates. Synthesis of Fiscalin B
  作者：Fernando Hernández、Félix L. Buenadicha、Carmen Avendaño、Mónica Söllhuber

  DOI：10.1016/s0957-4166(02)00027-7

  日期：2002.1

  An excess of base allows the regio- and diastereoselective alkylation at C(4) of the glycine templates 1-methyl(isopropyl)-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones 9a and 9b without the need for N(2)-protecting groups. While the alkylation of 9a gave exclusively the 1,4-anti-isomers, the isopropyl derivative 9b required much longer reaction times and occurred with lower diastereoselectivity. Fiscalin B 3 was obtained by alkylation of 9b with N-Boc-3-indolylmethyl bromide followed by indole deprotection. (C) 2002 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.