(2-aminoethyl)(3-aminooxypropyl)carbamic acid tert-butyl ester | 182576-29-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2-aminoethyl)(3-aminooxypropyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(2-aminoethyl)-N-(3-aminooxypropyl)carbamate
• CAS: 182576-29-0
• 化学式: C₁₀H₂₃N₃O₃
• 分子量: 233.311
• InChiKey: ZWCAINKYIKBAKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  90.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-aminoethyl)(3-aminooxypropyl)carbamic acid tert-butyl ester 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 3-{Benzyl-[2-(benzyl-{6-[(dibenzylamino)-methyl]-pyridin-2-ylmethyl}-amino)-ethyl]-amino}-propan-1-ol
  参考文献：
  名称：

  Solution Phase Combinatorial Chemistry. Synthesis of Novel Linear Pyridinopolyamine Libraries with Potent Antibacterial Activity

  摘要：

  Novel linear pyridinopolyamine derivatives 1-3, 7, and 8 have been synthesized as scaffolds for combinatorial drug discovery. The mono-t-Boc- and monotosyl-protected linear scaffolds 1 and 2 were obtained by a Schiff base type cyclization of 2,6-pyridinedicarboxaldehyde (24) with monoprotected triamines 22 and 23 using Ni2+ as a metal template, followed by reductive cleavage and decomplexation in a one-pot procedure. The unprotected linear scaffold 3 was obtained by treating 1 with TFA, Scaffold 1 was also synthesized from the orthogonally protected pyridinopolyamine 7 which was constructed from 2,6-bis(bromomethylipyridine (29) in four steps. Selective deprotection of the key intermediate 7 afforded 8, which was further selectively deprotected to give scaffold 1. A combinatorial chemistry strategy involving solution phase simultaneous addition of functionalities (SPSAF) is described. Thirteen high-purity tertiary amine libraries 19-21) (total 1638 compounds) were synthesized by the SPSAF and fix last methodologies from linear polyamine scaffolds 1 and 2. All libraries were examined by TLC, purified by chromatographic techniques, and characterized by H-1 NMR and ESI RIS spectral data. A fur last methodology was utilized to minimize chemical reactions and perform SAR studies directly on libraries. Several first-round sublibraries of scaffold 1 containing 126 compounds each, exhibited potent antibacterial activity with MICs of 1-12 mu M against Streptococcus pyogenes and Escherichia coli imp(-).

  DOI：

  10.1021/jo970535j
• 作为产物：
  描述：

  2-[2-[Benzyl(3-hydroxypropyl)amino]ethyl]isoindole-1,3-dione 在 palladium on activated charcoal 氢气 、 三乙胺 、 三苯基膦 、 肼 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 25.0~45.0 ℃ 、379.21 kPa 条件下， 反应 22.0h， 生成 (2-aminoethyl)(3-aminooxypropyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Solution-Phase Synthesis of Novel Linear Oxyamine Combinatorial Libraries with Antibacterial Activity

  摘要：

  Use of solution phase combinatorial library synthesis led to the discovery of several oxyamine-containing antibacterial compounds. Solution-phase simultaneous addition of meta-substituted benzyl bromides and "fix-last" combinatorial strategies were used to prepare libraries. Additional structure-activity relationship studies were conducted by reductive cleavage of the oxyamine moiety and led to loss of antibacterial activity. Several single compounds were designed and synthesized on the basis of library screening results and were shown to have antibacterial activity.

  DOI：

  10.1021/jo971655u

文献信息

• Solution phase combinatorial chemistry I. synthesis of polyazacyclophane scaffolds and tertiary amine libraries
  作者：Haoyun An、P.Dan Cook

  DOI：10.1016/0040-4039(96)01627-9

  日期：1996.9

  Three novel unsymmetrical polyazacyclophane scaffolds 1–3 were efficiently synthesized in high yields by a new cyclization method followed by selective deprotection. Scaffold 2 was combinatorialized by solution phase simultaneous addition of functionalities to provide 16 pure tertiary amine libraries (total 1600 compounds).

  通过一种新的环化方法，然后进行选择性脱保护，可以高产率高效地合成了三种新型的非对称多氮杂氮杂环庚烷骨架1-3。通过溶液相的同时添加功能来组合支架2，以提供16个纯叔胺库（总共1600种化合物）。
• Solution Phase Combinatorial Chemistry. Discovery of Novel Polyazapyridinophanes with Potent Antibacterial Activity by a Solution Phase Simultaneous Addition of Functionalities Approach
  作者：Haoyun An、Lendell L. Cummins、Richard H. Griffey、Ramesh Bharadwaj、Becky D. Haly、Allister S. Fraser、Laura Wilson-Lingardo、Lisa M. Risen、Jacqueline R. Wyatt、P. Dan Cook

  DOI：10.1021/ja964153r

  日期：1997.4.1

  Chemical modification of pre-formed asymmetric polyazaphane scaffolds by simultaneous addition of Functionality (letters) in solution has been developed for the preparation of tertiary nitrogen-based combinatorial chemistry libraries. This approach has some significant advantages over the more commonly employed solid phase bead splitting/resction/mixing procedures for the preparation of libraries. Three novel, asymmetric polyazaphanes 32, 33, and 37 have been synthesized in high yields by an efficient cyclization of 2,6-bis(bronzomethyl)pyridine (31) with new orthogonally protected triamines 29, 30, and 35, respectively. Selective deprotection of 32, 33, and 37 provided mono-t-Boc-protected scaffolds 1-3 suitable for solution phase, simultaneous addition of functionalities. Model studies of small libraries of scaffold 2 using CZE analyses indicated that simultaneous addition of 10 benzylic bromide alkylating functionalities would result in libraries containing approximately equimolar amounts of all possible compounds. Sixteen purified tertiary amine libraries 4-19 (total complexity of 1600 compounds) were generated by this procedure from scaffold 2. A ''fix-last'' combinatorial method was devised to minimize chemical reactions. Several first-round sublibraries of scaffold 2, containing a mixture of 100 compounds, exhibited potent antimicrobial activities. Twenty single compounds 63-82 with uniform functionalities at the combinatorialized sites were synthesized. Some of these pure compounds were more active, while others were less active, compared with the parent mixtures 5 and 10.
• Solution Phase Combinatorial Chemistry. Synthesis of Novel Linear Pyridinopolyamine Libraries with Potent Antibacterial Activity
  作者：Haoyun An、Becky D. Haly、Allister S. Fraser、Charles J. Guinosso、P. Dan Cook

  DOI：10.1021/jo970535j

  日期：1997.7.1

  Novel linear pyridinopolyamine derivatives 1-3, 7, and 8 have been synthesized as scaffolds for combinatorial drug discovery. The mono-t-Boc- and monotosyl-protected linear scaffolds 1 and 2 were obtained by a Schiff base type cyclization of 2,6-pyridinedicarboxaldehyde (24) with monoprotected triamines 22 and 23 using Ni2+ as a metal template, followed by reductive cleavage and decomplexation in a one-pot procedure. The unprotected linear scaffold 3 was obtained by treating 1 with TFA, Scaffold 1 was also synthesized from the orthogonally protected pyridinopolyamine 7 which was constructed from 2,6-bis(bromomethylipyridine (29) in four steps. Selective deprotection of the key intermediate 7 afforded 8, which was further selectively deprotected to give scaffold 1. A combinatorial chemistry strategy involving solution phase simultaneous addition of functionalities (SPSAF) is described. Thirteen high-purity tertiary amine libraries 19-21) (total 1638 compounds) were synthesized by the SPSAF and fix last methodologies from linear polyamine scaffolds 1 and 2. All libraries were examined by TLC, purified by chromatographic techniques, and characterized by H-1 NMR and ESI RIS spectral data. A fur last methodology was utilized to minimize chemical reactions and perform SAR studies directly on libraries. Several first-round sublibraries of scaffold 1 containing 126 compounds each, exhibited potent antibacterial activity with MICs of 1-12 mu M against Streptococcus pyogenes and Escherichia coli imp(-).
• Solution-Phase Synthesis of Novel Linear Oxyamine Combinatorial Libraries with Antibacterial Activity
  作者：Pei-Pei Kung、Ramesh Bharadwaj、Allister S. Fraser、Daniel R. Cook、Andrew M. Kawasaki、P. Dan Cook

  DOI：10.1021/jo971655u

  日期：1998.3.1

  Use of solution phase combinatorial library synthesis led to the discovery of several oxyamine-containing antibacterial compounds. Solution-phase simultaneous addition of meta-substituted benzyl bromides and "fix-last" combinatorial strategies were used to prepare libraries. Additional structure-activity relationship studies were conducted by reductive cleavage of the oxyamine moiety and led to loss of antibacterial activity. Several single compounds were designed and synthesized on the basis of library screening results and were shown to have antibacterial activity.