ethyl 4-[3-[6-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pyridin-2-yl]-4,5,6,7-tetrahydroindazol-1-yl]benzoate | 224324-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-[3-[6-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pyridin-2-yl]-4,5,6,7-tetrahydroindazol-1-yl]benzoate
• CAS: 224324-79-2；154420-41-4
• 化学式: C₂₈H₂₉N₅O₂
• 分子量: 467.571
• InChiKey: VHYNBCLMKGKZNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-[3-[6-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pyridin-2-yl]-4,5,6,7-tetrahydroindazol-1-yl]benzoate 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 24.0h， 以73%的产率得到2-[1-(4-carboxyphenyl)-4,5,6,7-tetrahydroindazol-3-yl]-6-(2H-4,5,6,7-tetrahydroindazol-3-yl)pyridine
  参考文献：
  名称：

  Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 3. Unsymmetrically Substituted Tridentates and Ditopic Bis(tridentates) en Route to Singly Stranded Helicates

  摘要：

  A strategy for the synthesis of helical multinuclear complexes (helicates) of any length is outlined, making use of ditopic ligands to bridge between metals and monotopic ligands to cap the chain's termini. We present the syntheses of both ditopic and monotopic ligands with tridentate binding units for octahedral metals, in liposoluble and functionalized varieties. Of special interest are ligands bearing benzoic acid or toluic acid side-chains which can ionize and serve as counteranions. Several singly N(1)-substituted 2,6-bis(4,5,6,7-tetrahydroindazol-3-yl)pyridines were prepared by regioselective, chelation-controlled mono;ni-alkylation or -arylation of the tautomeric N,N'-H-2 parent compound. These were then either coupled with CH2 linkages to provide the ditopic ligands or were further N-functionalized to give unsymmetrically substituted capping ligands. The regiochemistry of the N-substitutions and the ring-to-ring conformations were ascertained by H-1 NMR spectra with and without added complexands (H+, D+, Zn2+, and Na+). The formation of a bis(ZnBr2) adduct confirmed the independence of the metal binding sites while Na+ formed the 2:2 helicate.

  DOI：

  10.1021/jo970815z
• 作为产物：
  描述：

  对氟苯甲酸乙酯 、 2,6-Bis(1H-4,5,6,7-tetrahydrobenzopyrazol-3-yl)pyridine 在 1.) K 作用下， 生成 2,6-Bis[1-(4-carboxyphenyl)-4,5,6,7-tetrahydrobenzopyrazol-3-yl]pyridine diethyl ester 、 ethyl 4-[3-[6-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pyridin-2-yl]-4,5,6,7-tetrahydroindazol-1-yl]benzoate
  参考文献：
  名称：

  Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 3. Unsymmetrically Substituted Tridentates and Ditopic Bis(tridentates) en Route to Singly Stranded Helicates

  摘要：

  A strategy for the synthesis of helical multinuclear complexes (helicates) of any length is outlined, making use of ditopic ligands to bridge between metals and monotopic ligands to cap the chain's termini. We present the syntheses of both ditopic and monotopic ligands with tridentate binding units for octahedral metals, in liposoluble and functionalized varieties. Of special interest are ligands bearing benzoic acid or toluic acid side-chains which can ionize and serve as counteranions. Several singly N(1)-substituted 2,6-bis(4,5,6,7-tetrahydroindazol-3-yl)pyridines were prepared by regioselective, chelation-controlled mono;ni-alkylation or -arylation of the tautomeric N,N'-H-2 parent compound. These were then either coupled with CH2 linkages to provide the ditopic ligands or were further N-functionalized to give unsymmetrically substituted capping ligands. The regiochemistry of the N-substitutions and the ring-to-ring conformations were ascertained by H-1 NMR spectra with and without added complexands (H+, D+, Zn2+, and Na+). The formation of a bis(ZnBr2) adduct confirmed the independence of the metal binding sites while Na+ formed the 2:2 helicate.

  DOI：

  10.1021/jo970815z

文献信息

• Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 2. Tridentates
  作者：Patrick van der Valk、Pierre G. Potvin

  DOI：10.1021/jo00086a029

  日期：1994.4

  A new, more reliable synthesis of tetraketone 4 was found. With (t)BuNHNH(2), PhNHNH(2), and 4-hydrazinobenzoic acid, it condensed to give mostly in,in-disubstituted derivatives (7ii-9ii) of the parent, C-linked 2,6-bis(pyrazol-3-yl)pyridine 5, along with some in,out materials. MeNHNH(2) also provided some out,out isomer (6oo). This same derivative was also produced by NaH-mediated methylation of 5 with CH3I, presumably via a Na+ chelate that disallowed access to the inner pyrazole nitrogens, and was able, as a tridentate, to solubilize solid sodium picrate (NaPic) into CDCl3, with H-1-NMR detection of the complex. In contrast, the bidentate in,out isomer did not solubilize NaPic. Similarly, ethyl bromoacetate produced 10oo and it also solubilized NaPic. Previously reported alkylations of 5 had also given out,out products that bound alkali metal ions. 10oo was hydrolyzed to the disalt 13oo. In the presence of ZnCl2, 1 reacted with PhNHNH(2) to give the out,out derivative 8oo, presumably through a metal-mediated activation of the inner carbonyls of 1. Though 8oo also solubilized NaPic, a better NMR spectrum was obtained by treatment with CF3COOD, which indicated multidentate binding of D+. The same phenomenon was also observed with the out,out diester 1 loo, which was obtained by the nucleophilic aromatic substitution by 5 of ethyl 4-fluorobenzoate, presumably via a Kf chelate that also disallowed in substitution. A mono-out-substituted product 12 was also isolated from this reaction. Apart from mechanistic arguments and the ability or inability to dissolve NaPic, the aromatic H-1-NMR regions were diagnostic of the regiochemistries: In all cases, the pyridine H-3/5 doublet lay upfield of the H-4 triplet for in,in. isomers and downfield for out,out isomers, while in,out isomers showed one doublet on either side of the triplet. The binding of Na+ or D+ by the out,out isomers resulted in shifts of the H-3/5 doublets to upfield positions. The deuteration of in,in isomers did not. This situation was analogous to that of the bidentates reported in the accompanying paper and was similarly interpreted in conformational terms, with support from MM2 calculations: Like terpyridine, the imino nitrogens of the out,out materials prefer anti orientations due to electronic and steric repulsions (calculated Delta G(syn-anti) > 2.7 kcal/mol between rotamers about each pyridine-pyrazole bond in 6oo and 7oo and about the out-substituted pyrazole-pyridine bonds of 6io and 7io), but they are forced into syn orientations upon binding Na+ or D+. This induces a shielding interaction between the pyridine H-3/5 and neighboring CH2 groups. This same shielding is present in any conformation of the in,in products and of the in-substituted side of in,out isomers, which are much closer in energy (/Delta G(syn-anti)/ less than or equal to 0.4 kcal/mol for any ring-ring bond in 6ii and 7ii and for the in-substituted pyrazole-pyridine bonds of 6io and 7io).
• Zadykowicz, Jerzy; Potvin, Pierre G., Inorganic Chemistry, 1999, vol. 38, # 10, p. 2434 - 2441
  作者：Zadykowicz, Jerzy、Potvin, Pierre G.

  DOI：——

  日期：——
• Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 3. Unsymmetrically Substituted Tridentates and Ditopic Bis(tridentates) en Route to Singly Stranded Helicates
  作者：Jerzy Zadykowicz、Pierre G. Potvin

  DOI：10.1021/jo970815z

  日期：1998.1.1

  A strategy for the synthesis of helical multinuclear complexes (helicates) of any length is outlined, making use of ditopic ligands to bridge between metals and monotopic ligands to cap the chain's termini. We present the syntheses of both ditopic and monotopic ligands with tridentate binding units for octahedral metals, in liposoluble and functionalized varieties. Of special interest are ligands bearing benzoic acid or toluic acid side-chains which can ionize and serve as counteranions. Several singly N(1)-substituted 2,6-bis(4,5,6,7-tetrahydroindazol-3-yl)pyridines were prepared by regioselective, chelation-controlled mono;ni-alkylation or -arylation of the tautomeric N,N'-H-2 parent compound. These were then either coupled with CH2 linkages to provide the ditopic ligands or were further N-functionalized to give unsymmetrically substituted capping ligands. The regiochemistry of the N-substitutions and the ring-to-ring conformations were ascertained by H-1 NMR spectra with and without added complexands (H+, D+, Zn2+, and Na+). The formation of a bis(ZnBr2) adduct confirmed the independence of the metal binding sites while Na+ formed the 2:2 helicate.