3-amino-2-<(1S)-1-tert-butyldimethylsilyloxyethyl>-3,4-dihydroquinazolin-4-one | 175085-35-5

• 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: 3-amino-2-<(1S)-1-tert-butyldimethylsilyloxyethyl>-3,4-dihydroquinazolin-4-one
• 英文别名: (S)-3-amino-2-(1-tert-butyldimethylsilyloxy)ethyl-quinazolin-4(3H)-one；3-amino-2-[(1S)-1-[tert-butyl(dimethyl)silyl]oxyethyl]quinazolin-4-one
• CAS: 175085-35-5
• 化学式: C₁₆H₂₅N₃O₂Si
• 分子量: 319.479
• InChiKey: UAHLTPUBRXSHPL-NSHDSACASA-N

物化性质

• 沸点：
  401.2±47.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-2-<(1S)-1-tert-butyldimethylsilyloxyethyl>-3,4-dihydroquinazolin-4-one 在 六甲基二硅氮烷 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 生成 2-[(1S)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-3-[(2S,3S)-2-phenyl-3-trimethylsilylaziridin-1-yl]quinazolin-4-one
  参考文献：
  名称：

  Desilylative elimination of the quinazolinone ring from 1-(4-oxoquinazolin-3-yl)-2-silylaziridines; preparation of an N–H aziridine in high enantiomeric excess by in situ nucleophilic addition to the derived azirine

  摘要：

  乙烯基硅烷的氮丙啶化 PhCHCHSiR3 (R = Me, Et, Ph) 与 对映体纯 3-乙酰氧基氨基喹唑啉酮 11 给出 相应的氮丙啶 12 [非对映异构体比例 (dr) 10-1]、18（13-1 博士）和 20（2-1 博士）。 从这些物质中脱甲硅烷基消除喹唑啉酮 在氰化物存在下与氟化铯反应生成氮丙啶 氮丙啶 14 通过氰化物加成到 3-未取代的氮丙啶上 13、原地制作。氮丙啶 14 的酰化 (S)-乙酰氧基丙酰氯得到 N-酰基氮丙啶16；之间的良好相关性 氮丙啶 12、18 和 20 的非对映异构体比例 每种情况下产生的 N-酰基氮丙啶 16 表明 中间体氮丙啶 13 在构型上是 稳定的。

  DOI：

  10.1039/a606092g
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 (S)-3-amino-2-(1-hydroxyethyl)quinazolin-4(3H)-one 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以80%的产率得到3-amino-2-<(1S)-1-tert-butyldimethylsilyloxyethyl>-3,4-dihydroquinazolin-4-one
  参考文献：
  名称：

  Desilylative elimination of the quinazolinone ring from 1-(4-oxoquinazolin-3-yl)-2-silylaziridines; preparation of an N–H aziridine in high enantiomeric excess by in situ nucleophilic addition to the derived azirine

  摘要：

  乙烯基硅烷的氮丙啶化 PhCHCHSiR3 (R = Me, Et, Ph) 与 对映体纯 3-乙酰氧基氨基喹唑啉酮 11 给出 相应的氮丙啶 12 [非对映异构体比例 (dr) 10-1]、18（13-1 博士）和 20（2-1 博士）。 从这些物质中脱甲硅烷基消除喹唑啉酮 在氰化物存在下与氟化铯反应生成氮丙啶 氮丙啶 14 通过氰化物加成到 3-未取代的氮丙啶上 13、原地制作。氮丙啶 14 的酰化 (S)-乙酰氧基丙酰氯得到 N-酰基氮丙啶16；之间的良好相关性 氮丙啶 12、18 和 20 的非对映异构体比例 每种情况下产生的 N-酰基氮丙啶 16 表明 中间体氮丙啶 13 在构型上是 稳定的。

  DOI：

  10.1039/a606092g

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。
• 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。
• The stereoselective synthesis of aziridine analogues of diaminopimelic acid (DAP) and their interaction with dap epimerase
  作者：Christopher M. Diaper、Andrew Sutherland、Bindu Pillai、Michael N. G. James、Paul Semchuk、John S. Blanchard、John C. Vederas

  DOI：10.1039/b513409a

  日期：——

  Aziridine analogues of diaminopimelic acid (DAP) have been prepared stereoselectively for the first time and evaluated as inhibitors of DAP epimerase. (2R,3S,3′S)-3-(3′-Aminopropane)aziridine-2,3′-dicarboxylate 4 was synthesised and shown to be a reversible inhibitor of DAP epimerase with an IC50 value of 2.88 mM. (2S,4S)- and (2S,4R)-2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (LL-azi-DAP 14 and DL-azi-DAP 29) were made as pure diastereomers, and both were shown to be irreversible inhibitors of DAP epimerase. LL-Azi-DAP 14 selectively binds to Cys-73 of the enzyme active site whereas DL-azi-DAP 29 binds to Cys-217 via attack of sulfhydryl on the methylene of the inhibitor aziridine ring. These observations are consistent with the two base mechanism proposed for the epimerisation of LL-DAP 1 and meso-DAP 2 by DAP epimerase.

  我们首次立体选择性地制备了二氨基亚庚酸（DAP）的氮丙啶类似物，并将其评估为 DAP 外切酶的抑制剂。合成了(2R,3S,3′S)-3-(3′-氨基丙烷)氮丙啶-2,3′-二甲酸酯 4，结果表明它是 DAP 表聚酶的可逆抑制剂，IC50 值为 2.88 mM。(2S,4S)-和(2S,4R)-2-(4-氨基-4-羧基丁基)氮丙啶-2-羧酸（LL-Azi-DAP 14 和 DL-azi-DAP 29）被制成纯非对映异构体，并被证明都是 DAP 表聚酶的不可逆抑制剂。LL-azi-DAP 14 可选择性地与酶活性位点的 Cys-73 结合，而 DL-azi-DAP 29 则通过巯基对抑制剂氮丙啶环亚甲基的攻击与 Cys-217 结合。这些观察结果与 DAP 表聚酶对 LL-DAP 1 和 meso-DAP 2 的表聚作用提出的双基机制是一致的。
• Atkinson, Robert S.; Williams, Paul J., Journal of the Chemical Society. Perkin transactions II, 1996, # 2, p. 205 - 212
  作者：Atkinson, Robert S.、Williams, Paul J.

  DOI：——

  日期：——
• Desilylative elimination of the quinazolinone ring from 1-(4-oxoquinazolin-3-yl)-2-silylaziridines; preparation of an N–H aziridine in high enantiomeric excess by in situ nucleophilic addition to the derived azirine
  作者：Robert S. Atkinson、Michael P. Coogan、Ian S. T. Lochrie

  DOI：10.1039/a606092g

  日期：——

  Aziridination of vinylsilanes PhCHCHSiR3 (R = Me, Et, Ph) with enantiopure 3-acetoxyaminoquinazolinone 11 gives the corresponding aziridines 12 [diastereoisomer ratio (dr) 10∶1], 18 (dr 13∶1) and 20 (dr 2∶1). Desilylative elimination of the quinazolinone from these aziridines by caesium fluoride in the presence of cyanide gives aziridine 14 by cyanide addition to the 3-unsubstituted azirine 13, produced in situ. Acylation of aziridine 14 with (S)-acetoxypropionyl chloride gives N-acylaziridine 16; the good correlation between the diastereoisomer ratios of aziridines 12, 18 and 20 and those of the N-acylaziridine 16 produced in each case suggests that intermediate azirine 13 is configurationally stable.

  乙烯基硅烷的氮丙啶化 PhCHCHSiR3 (R = Me, Et, Ph) 与 对映体纯 3-乙酰氧基氨基喹唑啉酮 11 给出 相应的氮丙啶 12 [非对映异构体比例 (dr) 10-1]、18（13-1 博士）和 20（2-1 博士）。 从这些物质中脱甲硅烷基消除喹唑啉酮 在氰化物存在下与氟化铯反应生成氮丙啶 氮丙啶 14 通过氰化物加成到 3-未取代的氮丙啶上 13、原地制作。氮丙啶 14 的酰化 (S)-乙酰氧基丙酰氯得到 N-酰基氮丙啶16；之间的良好相关性 氮丙啶 12、18 和 20 的非对映异构体比例 每种情况下产生的 N-酰基氮丙啶 16 表明 中间体氮丙啶 13 在构型上是 稳定的。