(S)-3-amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one | 182160-10-7

• 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: (S)-3-amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one
• 英文别名: 3-amino-2-[(1S)-1-hydroxy-2,2-dimethylpropyl]quinazolin-4-one
• CAS: 182160-10-7
• 化学式: C₁₃H₁₇N₃O₂
• 分子量: 247.297
• InChiKey: MLMPLBFQBAFAQU-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one 在 六甲基二硅氮烷 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 2-[(1S)-1-hydroxy-2,2-dimethylpropyl]-3-[[oxo(diphenyl)-lambda6-sulfanylidene]amino]quinazolin-4-one
  参考文献：
  名称：

  Synthesis of chiral sulfoximines derived from 3-aminoquinazolinones and their catalysis of enantioselective diethylzinc addition to aldehydes

  摘要：

  一系列亚砜通过铅四醋酸盐的氧化加成反应与3-氨基喹唑啉酮进行硫氧化胺化。在六甲基二硅氮的存在下，它们首次应用于对芳香醛的催化对映选择性加成，在2-甲氧基苯甲醛的情况下，产物的对映体纯度（ee）达到92%。

  DOI：

  10.1039/c1ob06205k
• 作为产物：
  描述：

  (S)-2-Acetoxy-3,3-dimethylbutansaeurechlorid 在 肼 作用下， 生成 (S)-3-amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Reagent- and chelation-controlled diastereoselective aziridination of electron-rich alkenes by 3-acetoxyamino-2-(1-hydroxy-2,2-dimethylprop-1-yl)-quinazolin-4(3H)-one

  摘要：

  在四氟化钛(IV)叔丁醇的存在下，标题中的3-乙氧基氨基喹唑啉酮能够完全的二氟选择性地对苯乙烯、丁二烯和茚进行腈化反应；通过X射线晶体学证明了苯乙烯衍生的腈化物6a的绝对构型，并且与涉及钛的配位控制的过渡态模型一致。

  DOI：

  10.1039/cc9960001935
• 作为试剂：
  描述：

  diethylzinc 、 肉桂醛 在 (S)-3-amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one 作用下， 以 甲苯 为溶剂， 反应 24.0h， 生成 (R)-1-phenylpent-1-en-3-ol 、 (S)-1-phenylpent-1-en-3-ol
  参考文献：
  名称：

  3-Aminoquinazolinones as chiral ligands in catalytic enantioselective diethylzinc and phenylacetylene addition to aldehydes

  摘要：

  A series of readily known enantiomerically pure 3-aminoquinazolinones 1a-d were synthesised from easily accessible chiral pool alpha-hydroxy acids and alpha-amino acids in only four steps without any requirement of chromatography. These quinazolinones were examined as chiral ligands for catalytic enantioselective diethylzinc and phenylacetylene additions to aldehydes. For enantioselective alkylations, the effects of temperature, solvent, diethylzinc and ligand criteria were analysed, and the desired chiral alcohols were obtained in up to 86% ee. 3-Aminoquinazolinones 1a-d were also shown to be very useful ligands in enantioselective alkynylations of aldehydes. Based upon the optimised conditions, the corresponding propargylic alcohols were obtained in up to 94% ee. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2014.04.019

文献信息

• 3-Aminoquinazoline–phosphine ligands and their ruthenium(II) complexes: application in catalytic hydrogenation and transfer hydrogenation reactions
  作者：Mustafa Kemal Yılmaz、Mustafa Keleş

  DOI：10.1007/s11243-018-0213-9

  日期：2018.4

  and microanalysis. The 3-aminoquinazolinone–phosphine ligands were found to coordinate with the Ru(II) center via their phosphorus and nitrogen atoms. The Ru(II) complexes were applied as catalysts for the hydrogenation and transfer hydrogenation of prochiral ketones. The results showed that these complexes are efficient transfer hydrogenation catalysts.

  摘要 制备了 3-氨基喹唑啉酮-膦前配体 (5a-e) 及其 Ru(II) 配合物 (6a-e)，并通过 NMR（1H、13C、31P1H}）、FTIR 和微量分析对其进行了表征。发现 3-氨基喹唑啉酮-膦配体通过其磷和氮原子与 Ru(II) 中心配位。Ru(II)配合物用作前手性酮加氢和转移加氢的催化剂。结果表明，这些配合物是有效的转移加氢催化剂。
• Aziridination of β-substituted styrene derivatives with 3-acetoxyaminoquinazolin-4(3H)-ones: probing transition state geometry from changes in diastereoselectivity
  作者：Robert S. Atkinson、John Fawcett、Ian S. T. Lochrie、Sabri Ulukanli、Thomas A. Claxton

  DOI：10.1039/b107327n

  日期：2002.3.25

  Reaction of (S)-3-acetoxyamino-2-[1-(t-butyldimethylsilyloxy)ethyl]quinazolin-4(3H)-one 5 (Q1NHOAc) with styrene and R(β)-substituted E-styrenes (R = SiMe3, Me, CH2Cl, CHCl2) gives the corresponding aziridines diastereoselectively. The diastereoselectivity increases in the same sense from 5 ∶ 1 → 20 ∶ 1 as the electron-withdrawing character of R increases [H(Me), CH2Cl, CHCl2] but is accompanied by a decrease in yield of aziridine. A similar increase in diastereoselectivity is found in the reaction of 3-acetoxyamino-2-(2,3,3-trimethylpropyl)quinazolin-4(3H)-one 38 (Q4NHOAc) with the same β-substituted styrenes.An explanation for these observations is offered based on a tighter, more symmetrical transition state for the aziridination of styrenes bearing the more electron-withdrawing β-substituents and is supported by SCF calculations.

  (S)-3-乙酰氧胺基-2-[1-(叔丁基二甲基硅氧基)乙基]喹唑啉-4(3H)-酮5 (Q1NHOAc)与苯乙烯及R(β)-取代的E-苯乙烯(R = SiMe3, Me, CH2Cl, CHCl2)的反应，可选择性地生成相应的氮丙啶。随着R的吸电子特性增强[H(Me), CH2Cl, CHCl2]，立体选择性从5:1增加到20:1，但氮丙啶的产率却降低。3-乙酰氧胺基-2-(2,3,3-三甲基丙基)喹唑啉-4(3H)-酮38 (Q4NHOAc)与相同的β-取代苯乙烯反应，也观察到类似的立体选择性增加。这些现象的解释基于更紧密、更对称的过渡态，用于带有更强吸电子β-取代基的苯乙烯的氮丙啶化，并通过SCF计算得到支持。
• Aziridination of cyclic dienes with enantiopure 3-acetoxyaminoquinazolin-4(3H)-ones
  作者：Robert S. Atkinson、Christopher K. Meades

  DOI：10.1039/b102592a

  日期：——

  Aziridination of cyclopentadiene and cyclohepta-1,3-diene with (S)-3-acetoxyamino-2-(3-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one 6 (Q1NHOAc) in the presence of titanium(IV) tert-butoxide in dichloromethane takes place highly diastereoselectively: X-ray structure determinations show that the preferred sense of diastereoselectivity in both cases is the same as that previously found for aziridination of butadiene with 6. Aziridination of cyclohexa-1,3-diene with 6 was less diastereoselective in dichloromethane solution but highly diastereoselective in acetonitrile: in this solvent two diastereoisomeric cis-4-(Q1-amino)cyclohexen-3-ols 27 and 28 were also obtained as by-products. The same two amino alcohols were obtained by ring-opening of the aziridine with acid and were each converted into Q1-free oxazolidinones having optical rotations which were similar in magnitude but opposite in sign.

  环戊二烯和环七烯-1,3-二烯与(S)-3-乙酸氧氨基-2-(3-羟基-2,2-二甲基丙基)喹唑啉-4(3H)-酮6 (Q1NHOAc) 在四氧化钛和二氯甲烷的存在下发生了高的非对映选择性：X射线结构分析显示，两种情况下的非对映选择性偏好与之前发现的对丁二烯与6的非对映选择性一致。环己烯-1,3-二烯与6的环化反应在二氯甲烷溶液中表现出较低的非对映选择性，但在乙腈中则表现出高度的非对映选择性：在这种溶剂中还获得了两个非对映异构体的顺式-4-(Q1-氨基)环己烯-3-醇27和28作为副产物。这两个氨醇通过酸催化环戊烯开环也获得，并被转化为不含Q1的噁唑烷酮，且它们的光旋度在大小上相似但符号相反。
• Carbon–hydrogen bond insertion reactions of 3-acetoxy-aminoquinazolin-4(3H)-ones with cyclic dienes: stereochemistry and mechanism
  作者：Robert S Atkinson、Christopher K Meades

  DOI：10.1016/s0040-4020(01)01246-7

  日期：2002.2

  cyclohexadienyl ring carbon has been correlated with that at the 6-position of the major aziridine diastereoisomer co-produced in the reaction. A mechanism involving concerted insertion into the C–H bond of the diene by QNHOAc is proposed with endo-overlap of both double bonds of the diene with the Q group in the transition state.

  2-取代的3-乙酰氧基氨基喹唑啉-4（3 H）-ones（QNHOAc）与环己-1,3-二烯或环己-1,4-二烯（2当量）的反应除了稳定的叠氮化产物外，还可以稳定通过将[QN̈：]插入双烯丙基CH键中而正式产生的二氢芳族副产物。发生类似的插入9,10-二氢蒽或v吨（1.5-2当量）的亚甲基CH键的过程。使用3- acetoxyamino -2 - [（小号）-2,2-二甲基-1-羟基丙基]喹唑啉-4（3 H ^） -酮2（Q 1在钛的存在下NHOAc）（IV）吨-丁氧基，完全非对映选择性地插入环己-1,3-二烯中，并且在环己二烯基环碳上的构型与反应中共同生成的主要氮丙啶非对映异构体的6位上的构型相关。提出了一种机制，该机制涉及通过QNHOAc一致地插入二烯的CH键中，二烯的两个双键均与Q基团处于过渡态时发生内重叠。
• Direct Stereoselective Aziridination of Cyclohexenols with 3-Amino-2-(trifluoromethyl)quinazolin-4(3<i>H</i> )-one in the Synthesis of Cyclitol Aziridine Glycosidase Inhibitors
  作者：Marta Artola、Shirley Wouters、Sybrin P. Schröder、Casper de Boer、Yurong Chen、Rita Petracca、Adrianus M. C. H. van den Nieuwendijk、Johannes M. F. G. Aerts、Gijsbert A. van der Marel、Jeroen D. C. Codée、Herman S. Overkleeft

  DOI：10.1002/ejoc.201801703

  日期：2019.2.14

  configurational and functional isomers are powerful covalent inhibitors of retaining glycosidases, and find application in fundamental studies on glycosidases, amongst others in relation to inherited lysosomal storage disorders caused by glycosidase malfunctioning. Few direct and stereoselective aziridination methodologies are known for the synthesis of cyclophellitol aziridines. Herein, we present our studies

  环酚醇氮丙啶及其构型和功能异构体是保留糖苷酶的强大共价抑制剂，可用于糖苷酶的基础研究，其中包括与糖苷酶功能障碍引起的遗传性溶酶体贮积症相关的研究。很少有直接和立体选择性的氮丙啶化方法可用于合成环酚醇氮丙啶。在此，我们介绍了我们对各种构型和功能性环己烯醇等排体的直接 3-氨基-2-(三氟甲基)喹唑啉-4(3H)-one 介导的氮丙啶化作用范围的研究。我们证明了烯丙基或高烯丙基羟基可以通过氢键引导氮丙啶化反应，并且空间位阻在反应的非对映选择性中起着关键作用。