3-<(S)-2-Acetoxypropanoyl>amino-2-diphenylmethyl-3,4-dihydroquinazolin-4-one | 178422-79-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-<(S)-2-Acetoxypropanoyl>amino-2-diphenylmethyl-3,4-dihydroquinazolin-4-one
• 英文别名: [(2S)-1-[(2-benzhydryl-4-oxoquinazolin-3-yl)amino]-1-oxopropan-2-yl] acetate
• CAS: 178422-79-2
• 化学式: C₂₆H₂₃N₃O₄
• 分子量: 441.486
• InChiKey: KGRRSASHIRBXLD-KRWDZBQOSA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-<(S)-2-Acetoxypropanoyl>amino-2-diphenylmethyl-3,4-dihydroquinazolin-4-one 在 吡啶 作用下， 生成
  参考文献：
  名称：

  3-Di-[(S)-2-acetoxypropanoyl]aminoquinazolin-4(3H)-ones: stereostructure and application in kinetic resolution of amines

  摘要：

  Whereas 3-diacylaminoquinazolin-4(3H)-ones (DAQs) have been previously shown to undergo rapid exo/endo-endo/exo conformational interconversion of their imide carbonyl groups, the title DAQs are believed to exist in one single exo/endo form and consequently their N-N bonds are chiral axis: one of these DAQs, substituted with a diphenylmethyl group on the Q-2 position, reacts preferentially with one enantiomer of racemic 2-methyl-piperidine at the 2-acetoxypropanoyl imide carbonyl group (ee 94%). (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)00139-8
• 作为产物：
  描述：

  N-(2-Hydrazinocarbonyl-phenyl)-2,2-diphenyl-acetamide 在 吡啶 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 53.0h， 生成 3-<(S)-2-Acetoxypropanoyl>amino-2-diphenylmethyl-3,4-dihydroquinazolin-4-one
  参考文献：
  名称：

  The N–N bond as a chiral axis: 3-diacylaminoquinazolinones as chiral acylating agents

  摘要：

  3-Diacylaminoquinazolinones 10 and 15 have high enough barriers to rotation around their N-N bonds to allow separation of each into diastereoisomers. Interconversion of diastereoisomers 10a and 10b occurs on heating in boiling toluene and thermodynamic parameters for this process have been measured, The barriers to rotation around the N-N bonds in analogous monoacylaminoquinazolinones are not sufficient to permit isolation of stereoisomers at room temperature unless the exocyclic nitrogen is additionally substituted e.g. by an alkyl group as in 28, X-Ray crystal structure determinations carried out on 10a, 10b, 15a and 28b confirm the presence of chiral axes, Reaction of both diastereoisomers 15a and 15b with 1-phenylethylamine takes place with exclusive reaction at the 1-acetoxypropionyl carbonyl group and with partial kinetic resolution: the preferred sense of enantioselectivity obtained is dominated by the N-N axis.

  DOI：

  10.1039/p19960001047

文献信息

• Kinetic resolution of amines with enantiopure 3-N,N-diacylaminoquinazolin-4(3H)-ones
  作者：Al-Sehemi, Abdullah G.、Atkinson, Robert S.、Fawcett, John

  DOI：10.1039/b105917n

  日期：2002.1.7

  The title compounds (DAQs) are chiral when the two N-acyl groups are different because of the absence of rotation around the N–N bond (a chiral axis). Enantiopure DAQs have been obtained by incorporation of a chiral centre in enantiopure form either into the substituent at the Q2-position or into one of the N-acyl groups, or into both, followed by separation of diastereoisomers. This separation is unnecessary in one case because conversion of the N-monoacylaminoquinazolinone (MAQ) into the DAQ is completely diastereoselective. Neither is separation of diastereoisomers necessary with 3-[N,N-di-(S)-2-acetoxypropanoylamino]-2-diphenylmethylquinazolin-4(3H)-one 37a: this DAQ 37a has its N–N bond rendered a chiral axis by the bias in its imide moiety wholly in favour of one exo/endo conformation.The high chemoselectivity exhibited by N,N-diacetyl- or N,N-dibenzoylaminoquinazolinones in reaction with the less hindered of two secondary amines (pyrrolidine in the presence of 1 eq. of piperidine) has a stereoselective counterpart: reaction of the above enantiopure DAQs enantioselectively with racemic amines leading to kinetic resolution. Using 1 eq. of DAQ and 2 eq. of amine, both the derivatised and unreacted amine enantiomers are recovered with high enantiomeric excess (ee) (better than 90% ee in some cases). Some of the higher ees are found in the recovered amides where non-chemoselective attack on both N-acyl groups of the DAQ has occurred: from the opposite configurations of the amine component in the two amides and from the low enantiopurity of the recovered unreacted amine, reaction of each of the N-acyl groups with complementary enantiomers of the amine is occurring (parallel kinetic resolution).Although higher ees are, in general, obtained using secondary amines, high ees are obtained in some cases using 1-phenylethylamine and, in particular, amino acid esters (valine and alanine).The sense of enantioselectivity in the reactions of these DAQs with amines is controlled by the configuration of the N–N axis: replacing the Q group in an N-(S)-2-acetoxypropanoyl-N-acetyl-bearing DAQ by phthalimide, thus eliminating the N–N chiral axis, drastically reduces the level of kinetic resolution.

  标题化合物(DAQs)在两个N-酰基团不同时是手性的，因为N-N键（一个手性轴）缺乏旋转。通过将手性中心以手性形式引入Q2-位点的取代基或其中一个N-酰基团，或两者中，随后分离diastereoisomers，得到了纯对映体的DAQs。在一个情况下，这种分离是不必要的，因为将N-单酰胺基喹唑啉酮(MAQ)转化为DAQ是完全立体选择性的。对于3-[N,N-di-(S)-2-乙酰氧基丙酰胺基]-2-二苯甲基喹唑啉-4(3H)-酮37a，也不需要分离diastereoisomers：这个DAQ 37a通过其亚胺部分的偏向完全倾向于一个exo/endo构象，使其N-N键成为一个手性轴。N,N-二乙酰基或N,N-二苯甲酰氨基喹唑啉酮在与两个次级胺中较少受到阻碍的胺（在存在1 eq.的哌啶的情况下使用吡咯烷）反应时表现出高度的化学选择性，这在立体选择性上有对应：上述纯对映体的DAQs与外消旋胺反应，导致动力学拆分。使用1 eq.的DAQ和2 eq.的胺，衍生化的和未反应的胺对映体都以高对映体过量（ee）回收（在一些情况下优于90% ee）。在一些回收的酰胺中发现较高的ee，其中非化学选择性地攻击DAQ的两个N-酰基团：从两个酰胺中胺组分的相反构型和回收的未反应胺的低对映纯度，每个N-酰基团与胺的互补对映体反应（并行动态拆分）。尽管通常使用次级胺得到较高的ee，但在某些情况下使用1-苯乙胺，特别是氨基酸酯（缬氨酸和丙氨酸）得到高ee。这些DAQs与胺反应的对映选择性的方向受N-N轴配置的控制：在带有N-(S)-2-乙酰氧基丙酰基-N-乙酰基的DAQ中，通过用邻苯二甲酰亚胺替换Q组，从而消除N-N手性轴，显著降低了动力学拆分的水平。
• The N–N bond as a chiral axis: 3-(diacylamino)quinazolin-4(3H)ones as chiral acylating agents
  作者：Robert S. Atkinson、Emma Barker、Christopher J. Price、David R. Russell

  DOI：10.1039/c39940001159

  日期：——

  Two diasteroisomers of 3-(diacylamino)quinazolinone 5 are separated and identified by crystal structure determinations which confirm the presence of an N–N chiral axis: one diastereoisomer of enantiopure 8 reacts with racemic 1-phenylethylamine exclusively at the 2-acetoxypropanoyl imide carbonyl group and with kinetic resolution to give a 3.6 : 1 ratio of diastereoisomers of 10.

  通过晶体结构测定，确认了 NâN 手性轴的存在，从而分离并识别出 3-（二酰氨基）喹唑啉酮 5 的两种非对映异构体：其中一种非对映异构体 8 与外消旋 1-苯基乙胺反应，只在 2-乙酰氧基丙酰亚胺羰基上发生反应，并通过动力学解析得到非对映异构体 10，比例为 3.6:1。
• 3-Di-[(S)-2-acetoxypropanoyl]aminoquinazolin-4(3H)-ones: stereostructure and application in kinetic resolution of amines
  作者：Abdullah G Al-Sehemi、Robert S Atkinson、John Fawcett、David R Russell

  DOI：10.1016/s0040-4039(00)00139-8

  日期：2000.3

  Whereas 3-diacylaminoquinazolin-4(3H)-ones (DAQs) have been previously shown to undergo rapid exo/endo-endo/exo conformational interconversion of their imide carbonyl groups, the title DAQs are believed to exist in one single exo/endo form and consequently their N-N bonds are chiral axis: one of these DAQs, substituted with a diphenylmethyl group on the Q-2 position, reacts preferentially with one enantiomer of racemic 2-methyl-piperidine at the 2-acetoxypropanoyl imide carbonyl group (ee 94%). (C) 2000 Elsevier Science Ltd. All rights reserved.
• The N–N bond as a chiral axis: 3-diacylaminoquinazolinones as chiral acylating agents
  作者：Robert S. Atkinson、Emma Barker、Paul J. Edwards、Gordon A. Thomson

  DOI：10.1039/p19960001047

  日期：——

  3-Diacylaminoquinazolinones 10 and 15 have high enough barriers to rotation around their N-N bonds to allow separation of each into diastereoisomers. Interconversion of diastereoisomers 10a and 10b occurs on heating in boiling toluene and thermodynamic parameters for this process have been measured, The barriers to rotation around the N-N bonds in analogous monoacylaminoquinazolinones are not sufficient to permit isolation of stereoisomers at room temperature unless the exocyclic nitrogen is additionally substituted e.g. by an alkyl group as in 28, X-Ray crystal structure determinations carried out on 10a, 10b, 15a and 28b confirm the presence of chiral axes, Reaction of both diastereoisomers 15a and 15b with 1-phenylethylamine takes place with exclusive reaction at the 1-acetoxypropionyl carbonyl group and with partial kinetic resolution: the preferred sense of enantioselectivity obtained is dominated by the N-N axis.