Preparation of indole containing building blocks for the regiospecific construction of indole appended pyrazoles and pyrroles

Gupton, John T.; Telang, Nakul; Gazzo, Dominic F.; Barelli, Peter; Lescalleet, Kristin; Fagan, Jonathan W.; Mills, B.; Finzel, Kara; Kanters, R. P. F.; Crocker, Kyle R.; Dudek, Sean T.; Lariviere, Corinne M.; Smith, Stanton Q.; Keertikar, Kartik M.

doi:10.1016/j.tet.2013.05.045

Cited by 14 publications

(6 citation statements)

References 19 publications

(21 reference statements)

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“…Sodium hydride (60% suspension in mineral oil, 280 mg, 7 mmol) was washed with hexane (3 × 2 mL), and THF (24 mL) was added. The suspension was cooled to 0 °C under an argon atmosphere, and 4-indol-3-yl-1H-pyrazole 42 (549 mg, 3 mmol) was added in one portion. The mixture was stirred for 30 min at 0 °C, and methyl iodide (1.87 g, 6.6 mmol) was added.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Rh(II)-Catalyzed Ring Expansion of Pyrazoles with Diazocarbonyl Compounds as a Method for the Preparation of 1,2-Dihydropyrimidines

et al. 2018

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A high yield synthesis of 1,2-dihydropyrimidines by the Rh(II)-catalyzed reaction of diazocarbonyl compounds with 1,4-di- and 1,4,5-trisubstituted pyrazoles is reported. This reaction represents the first example of a carbenoid insertion into a N-N bond and provides a novel approach to 4-unsubstituted 1,2-dihydropyrimidines with a broad range of functional group tolerance. According to DFT calculations, the pyrazole ring expansion proceeds via the sequential formation of the metal-bound pyrazolium ylide, metal-free pyrazolium ylide, and 1,5-diazahexatriene followed by 1,6-cyclization.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Rh(II)-Catalyzed Ring Expansion of Pyrazoles with Diazocarbonyl Compounds as a Method for the Preparation of 1,2-Dihydropyrimidines

et al. 2018

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“…3-Ethynyl-1-methyl-1H-indole ( 6 ). Yield: 113 mg (73%); Spectral characteristics are the same as previously published [ 64 ].…”

Section: Methodsmentioning

confidence: 94%

Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles

et al. 2023

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It has been found that the addition of CH2CN− anion to the carbonyl group of acylethynylpyrroles, generated from acetonitrile and t-BuOK, results in the formation of acetylenic alcohols, which undergo unexpectedly easy (room temperature) decomposition to ethynylpyrroles and cyanomethylphenylketones (retro-Favorsky reaction). This finding allows a robust synthesis of ethynylpyrroles in up to 95% yields to be developed. Since acylethynylpyrroles became available, the strategy thus found makes ethynylpyrroles more accessible than earlier. The quantum-chemical calculations (B2PLYP/6-311G**//B3LYP/6-311G**+C-PCM/acetonitrile) confirm the thermodynamic preference of the decomposition of the intermediate acetylenic alcohols to free ethynylpyrroles rather than their potassium derivatives.

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“…utilized indole‐attached vinamidinium salt ( 171 ), vinylogous amide ( 174 ) and chloroenal ( 175 ) to regioselectively construct the 3‐pyrazolyl indole derivatives ( 172 , 176 & 177 ) (Scheme 31). [75] Indolyl vinamidinium hexfluorophosphate ( 171 ) was prepared by treating indole‐3‐acetic acid ( 170 ) with the Vilsmeier‐Haack‐Arnold reagent followed by aqueous sodium hexafluorophosphate. Compound 171 reacted with monosubstituted hydrazines in the presence of a mild base such as Na 2 CO 3 in EtOH and selectively formed 1,4‐isomer ( 172 ) whose indole moiety is introduced to the C4‐ position of pyrazole.…”

Section: Direct‐linked Indole‐c3 Pyrazole Hybridsmentioning

confidence: 99%

“…). [75] Indolyl vinamidinium hexfluorophosphate (171) was prepared by treating indole-3-acetic acid (170) with the Vilsmeier-Haack-Arnold reagent followed by aqueous sodium hexafluorophosphate. Compound 171 reacted with monosubstituted hydrazines in the presence of a mild base such as Na 2 CO 3 in EtOH and selectively formed 1,4-isomer (172) whose indole moiety is introduced to the C4-position of pyrazole.…”

Section: Chemistryselectmentioning

confidence: 99%

Recent Developments in the Synthesis of Indole‐Pyrazole Hybrids

et al. 2022

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Indole and pyrazole are two important scaffolds in the field of medicinal chemistry. Compounds bearing indole and/or pyrazole moiety have been extensively investigated for a wide range of biological applications. Of them, compounds containing both indole and pyrazole moieties (also termed as indole‐pyrazole hybrids) are of particular interest since synergistic pharmacological activities may be gained comparing to those with each individual pharmacophore. Indole‐pyrazole hybrids can be classified into two general classes of direct‐linked hybrids and spacer‐linked hybrids. For each class, it can be sub‐divided into indole‐C2 pyrazole hybrids, indole‐C3 pyrazole hybrids and indole‐C4/5/6/7 pyrazole hybrids based on the substitution position of pyrazole on the indole moiety. Many types of indole‐pyrazole hybrids have been reported with good antimicrobial, anticancer, antitumor, anti‐inflammatory, anti‐oxidant activities etc. However, no papers have been noted to comprehensively summarize the chemical synthesis of these important indole‐pyrazole hybrids as bioactive compounds except for a few reviews focusing on the synthesis of each individual indole‐ and pyrazole‐containing derivatives. Thus, we here present a comprehensive and updated review focusing on the progress of chemical synthesis of all types of indole‐pyrazole hybrids in order to provide a better understanding of the indole‐pyrazole hybrids to researchers in the fields of synthetic chemistry and to facilitating drug development.

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Preparation of indole containing building blocks for the regiospecific construction of indole appended pyrazoles and pyrroles

Abstract: The preparation of an indole appended vinamidinium salt, an indole appended vinylogous amide and an indole appended chloroenal are described. The subsequent regiospecific conversion of these indole containing building blocks to functionalized pyrazoles and pyrroles is detailed.

Cited by 14 publications

References 19 publications

Rh(II)-Catalyzed Ring Expansion of Pyrazoles with Diazocarbonyl Compounds as a Method for the Preparation of 1,2-Dihydropyrimidines

Rh(II)-Catalyzed Ring Expansion of Pyrazoles with Diazocarbonyl Compounds as a Method for the Preparation of 1,2-Dihydropyrimidines

Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles

Recent Developments in the Synthesis of Indole‐Pyrazole Hybrids

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