Synthesis and autooxidation of 2-amino-1,3-dialkylindoles

Кост, А. Н.; Portnov, Yu. N.; Golubeva, G. A.; Попова, А. Н.; Mushket, B.

doi:10.1007/bf00742837

Cited by 4 publications

(5 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hydrochloride salt of 4 was isolated and found to be inactive; its free-base, however, was exceedingly unstable, leading to the rapid formation of the overoxidized 3-ol derivative 5 , presumably via autoxidation 66 (Scheme 1), which was also inactive in primary screens.…”

Section: Resultsmentioning

confidence: 99%

“…With 3-pentyl-quinoline-2-amine as our point of departure, we initially targeted the ring-contracted 2-amino-3-alkylindole analogue 4 , accessed via sequential C-alkylation of commercially available 2-nitrophenylacetonitrile, reduction of the 2-nitro group, and Brønsted acid-promoted, microwave-assisted intramolecular cyclization (Scheme 1 ). The hydrochloride salt of 4 was isolated and found to be inactive; its free-base, however, was exceedingly unstable, leading to the rapid formation of the overoxidized 3-ol derivative 5 , presumably via autoxidation 66 (Scheme 1 ), which was also inactive in primary screens.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Human Toll-Like Receptor 8-Selective Agonistic Activities in 1-Alkyl-1H-benzimidazol-2-amines

et al. 2014

View full text Add to dashboard Cite

Toll-like receptor (TLR)-8 agonists strongly induce the production of T helper 1-polarizing cytokines and may therefore serve as promising candidate vaccine adjuvants, especially for the very young and the elderly. Earlier structure-based ligand design led to the identification of 3-pentyl-quinoline-2-amine as a novel, human TLR8-specific agonist. Comprehensive structure–activity relationships in ring-contracted 1-alkyl-1H-benzimidazol-2-amines were undertaken, and the best-in-class compound, 4-methyl-1-pentyl-1H-benzo[d]imidazol-2-amine, was found to be a pure TLR8 agonist, evoking strong proinflammatory cytokine and Type II interferon responses in human PBMCs, with no attendant CD69 upregulation in natural lymphocytic subsets. The 1-alkyl-1H-benzimidazol-2-amines represent a novel, alternate chemotype with pure TLR8-agonistic activities and will likely prove useful not only in understanding TLR8 signaling but also perhaps as a candidate vaccine adjuvant.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Human Toll-Like Receptor 8-Selective Agonistic Activities in 1-Alkyl-1H-benzimidazol-2-amines

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It is known that in solutions of aminoindoles a tautomeric equilibrium exists between the aminoindole and the iminoindoline forms 1 and 6 [4]. Furthermore aminoindoles are capable of radical reactions, for example with oxygen [5]. Consequently it may be suggested that the reaction forming compound 5 begins with a one-electron transfer, after which follows proton exchange, interaction with a second molecule of 1d, opening of the ring, and stabilization of the reaction product (Scheme 1).…”

mentioning

confidence: 97%

Interaction of 2-Aminoindoles with Tetracyanoethylene. 2. 3-Dicyano-methylene-2-iminoindolines

Sadovoy

Golubeva

2005

Chem Heterocycl Compd

Self Cite

View full text Add to dashboard Cite

A. V. Sadovoy and G. A. Golubeva 3-Dicyanomethylene-2-iminoindolines are obtained on interacting 2-aminoindoles with tetracyanoethylene in acidic medium.We reported previously [1], that on interacting 2-aminoindoles 1 with tetracyanoethylene 2 in neutral or weakly alkaline medium 3,4-dicyano-2-imino-1,2-dihydro-α-carbolines 3 or 2-amino-3,4-dicyano-α-carbolines 3' are formed. However, according to [2] the oxygen analogs of 2-aminoindoles, the oxindoles, react with compound 2 differently, forming 3-dicyanomethylene derivatives. Assuming that in these processes the acidity of the medium is important, we attempted to obtain dicyanomethylene derivatives of 2-aminoindoles under other conditions.It turned out that on heating 2-aminoindoles 1a-c with compound 2 in an acidic medium for 10-60 min in reality the expected 3-dicyanomethylene-2-iminoindolines 4a-c are formed in good yield. They are easily purified, and are well crystallizing compounds, colored an intense red-violet. In their IR spectra (Table 1) bands were present for the stretching vibrations of conjugated C≡N groups and absorption bands for N-H bonds were absent. The 1 H and 13 C NMR spectra did not contradict the proposed structure, and in the mass spectra (Table 1) there was the expected peak for the molecular ion. The fragmentation confirmed the proposed structures.The shade of the coloring of solutions of these compounds depends on the solvent used. Solutions in chloroform and dichloromethane have a red-violet color, but in oxygen-containing solvents (alcohol, acetone, dioxane, DMSO) they are red. The positions of the absorption band maxima in the UV spectra of compounds 4a,c in DMSO and chloroform are practically unchanged, but in DMSO the absorption in the long wave portion of the spectrum is significantly weakened, and on the other hand the trough between the absorption bands at λ ≈ 430 nm ( Fig. 1) is reduced, which leads to a weakening of the blue component of the color. The reason for this effect may probably be coordination of one solvent molecule with the carbon atoms of both nitrile groups of the 4 molecule. Such coordination must lead to some disturbance of the planarity of the dicyanomethylene fragment and consequently to a reduction in the conjugation in molecule 4.

show abstract

“…This strategy was further developed by us in palladium-catalyzed MCRs to access amidines, where amines served as nucleophiles (Scheme , eq 3) . We expect the intramolecular nucleophilic attack on the in situ formed ketenimines, albeit without preceding reports, could furnish ring closure toward 2-aminoindoles, which, subsequently, is oxidized by O 2 allowing access to 2-amino-3-hydroxy-3 H -indoles quickly (Scheme , eq 4) . Herein, we wish to report such a synthetic pathway, which represents not only a key compliment to the sporadic synthetic methods toward 2-amino-3-hydroxy-3 H -indoles but also progress in N -tosylhydrazone, isonitrile, and ketenimine chemistry.…”

mentioning

confidence: 99%

“…After the dissociation of palladium to enter the catalytic cycle, the intramolecular attack of ketenimine 4 by the amino in the phenyl ring furnished the ring closure leading to 2-aminoindole 5 . Finally, the oxidation of 5 by O 2 produced the final product 2-amino-3-hydroxy-3 H -indole via the formation of 2-amino-3-peroxy-3 H -indole …”

mentioning

confidence: 99%

Synthesis of 2-Amino-3-hydroxy-3H-indoles via Palladium-Catalyzed One-Pot Reaction of Isonitriles, Oxygen, and N-Tosylhydrazones Derived from 2-Acylanilines

et al. 2017

View full text Add to dashboard Cite

A cyanide-free one-pot procedure was developed to access 2-amino-3-hydroxy-3H-indoles, which involved: (1) in situ formation of ketenimines by the reaction of N'-(1-(2-aminophenyl)ethylidene)-p-tosylhydrazones with isonitriles; (2) the intramolecular nucleophilic attack of ketenimines by the amino in phenyl furnishing the ring closure leading to 2-aminoindoles; (3) the oxidation of 2-aminoindoles by O leading to 2-amino-3-hydroxy-3H-indoles. This strategy represents not only a key compliment to the sporadic synthetic methods toward 2-amino-3-hydroxy-3H-indoles but also progress in N-tosylhydrazone, isonitrile, and ketenimine chemistry.

show abstract

Synthesis and autooxidation of 2-amino-1,3-dialkylindoles

Cited by 4 publications

References 6 publications

Human Toll-Like Receptor 8-Selective Agonistic Activities in 1-Alkyl-1H-benzimidazol-2-amines

Human Toll-Like Receptor 8-Selective Agonistic Activities in 1-Alkyl-1H-benzimidazol-2-amines

Interaction of 2-Aminoindoles with Tetracyanoethylene. 2. 3-Dicyano-methylene-2-iminoindolines

Synthesis of 2-Amino-3-hydroxy-3H-indoles via Palladium-Catalyzed One-Pot Reaction of Isonitriles, Oxygen, and N-Tosylhydrazones Derived from 2-Acylanilines

Contact Info

Product

Resources

About