[4-(2-Nitro-benzenesulfonylamino)-butyl]-[3-(2-nitro-benzenesulfonylamino)-propyl]-carbamic acid tert-butyl ester | 182576-26-7

• 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: [4-(2-Nitro-benzenesulfonylamino)-butyl]-[3-(2-nitro-benzenesulfonylamino)-propyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[4-[(2-nitrophenyl)sulfonylamino]butyl]-N-[3-[(2-nitrophenyl)sulfonylamino]propyl]carbamate
• CAS: 182576-26-7
• 化学式: C₂₄H₃₃N₅O₁₀S₂
• 分子量: 615.686
• InChiKey: MXGBBZQTYMDCCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  230
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [4-(2-Nitro-benzenesulfonylamino)-butyl]-[3-(2-nitro-benzenesulfonylamino)-propyl]-carbamic acid tert-butyl ester 在 potassium carbonate 、 caesium carbonate 、 苯硫酚 、 三氟乙酸 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 3,12-Bis-(3-bromo-benzyl)-3,7,12,18-tetraaza-bicyclo[12.3.1]octadeca-1(18),14,16-triene
  参考文献：
  名称：

  Solution Phase Combinatorial Chemistry. Discovery of Novel Polyazapyridinophanes with Potent Antibacterial Activity by a Solution Phase Simultaneous Addition of Functionalities Approach

  摘要：

  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.

  DOI：

  10.1021/ja964153r
• 作为产物：
  描述：

  亚精胺 在 ammonium hydroxide 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.0h， 生成 [4-(2-Nitro-benzenesulfonylamino)-butyl]-[3-(2-nitro-benzenesulfonylamino)-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Solution Phase Combinatorial Chemistry. Discovery of Novel Polyazapyridinophanes with Potent Antibacterial Activity by a Solution Phase Simultaneous Addition of Functionalities Approach

  摘要：

  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.

  DOI：

  10.1021/ja964153r

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）。
• Synthesis of novel polyazadipyridinocyclophane scaffolds and their application for the generation of libraries
  作者：Tingmin Wang、Haoyun An、Timothy A. Vickers、Ramesh Bharadwaj、P.Dan Cook

  DOI：10.1016/s0040-4020(98)00441-4

  日期：1998.7

  Six novel, asymmetric, 19- to 26-membered polyazadipyridinocyclophane scaffolds 1-6 have been synthesized in high yields by an efficient cyclization of ditosylate 39 with the appropriate six fully protected triamines 40-45, followed by removing the 2-nitrobenzenesulfonyl protecting groups. intermediate 39 was synthesized by the Mitsunobu reaction of 2-nitrobenzenesulfonamide (37) with 2,6-pyridinedimethanol (36), and a subsequent tosylation of the resulted diol 38. The fully protected asymmetric triamines 41 and 43 were prepared from the corresponding commercially available triamines 52 and 53. A new synthetic route was developed for the synthesis of the protected asymmetric triamines 44 and 45. Ah reactions were carried out at room temperature in high yields. The reaction of t-Boc-protected scaffold 1, having three reactive sites, with nine benzylic bromides and bromoacetonitrile, using a solution phase simultaneous addition of functionalities combinatorial strategy, Save t-Boc-protected library 7 containing 1000 compounds. Deprotection of library 7 generated the intermediate library 8 with one reactive site. Subsequent reactions at the unsubstituted position of 8 with various functionalities by four types of reactions gave sixteen final libraries 9-24. Libraries 7-24 have different functionalities at the fixed position, and each of them contains 1000 compounds. The reaction of scaffold 2, having four reactive sites without protecting groups, with six sets of polar functionalities afforded eleven diverse libraries 25-35 containing 625 compounds in each library. Totally, twenty-nine libraries containing 24875 compounds were obtained. Eight libraries exhibited antibacterial activity against Escherichia coli imp(-) and Streptococcus pyogenes with the MIC's of 2 to 10-50 mu M. Seven libraries disrupted HIV-1 tat/TAR protein-RNA interactions with IC50's as low as 0.08 mu M. (C) 1998 Elsevier Science Ltd.All rights reserved.
• US6191273B1
  申请人：——

  公开号：US6191273B1

  公开（公告）日：2001-02-20