Three-component synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines from 1-aroyl-3,4-dihydroisoquinolines, electron-deficient alkynes and NH-acids

Miftyakhova, Almira R.; Sidakov, Matvey B.; Борисова, Т. Н.; Ilyushenkova, Valentina V.; Фахрутдинов, Артем Н.; Сорокина, Е. А.; Варламов, А. В.; Voskressensky, Leonid G.

doi:10.1016/j.tetlet.2022.153991

Cited by 9 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latest publications of our group have focused on the development and optimization of three-component syntheses of 5,6-dihydropyrrolo[2,1- a ]isoquinolines based on transformations of 1-aroyl-3,4-dihydroisoquinolines in the presence of electron-deficient alkynes (methylpropiolate and acetylacetylene) and CH or NH acids . The described domino reactions make it possible to obtain highly functionalized pyrrolo[2,1- a ]isoquinolines having pharmacophoric groups at position 3 (Scheme a).…”

Section: Resultsmentioning

confidence: 99%

“…13 4.00 (q, 2H, J = 6.9 Hz), 3.96−3.92 (m, 2H), 3.76−3.70 (m, 2H), 3.67 (s, 3H), 3.32−3.28 (m, 2H), 3.15− 3.06 (m, 2H), 1.32−1.27 (m, 6H), 1.21 (t, 3H, J = 6.9 Hz), 0.95 (t, 3H, J = 6.9 Hz) ppm. 13 19 ), 3.56 (s, 3H), 3.14 (t, 2H, J = 6.2 Hz), 3.08 (s, 3H) ppm. 13 (q, 2H, J = 6.9 Hz), 3.99 (q, 2H, J = 6.9 Hz), 3.81 (q, 2H, J = 6.9 Hz), 3.72 (s, 3H), 3.62 (s, 3H), 3.45 (q, 2H, J = 6.9 Hz), 3.13 (t, 2H, J = 6.4 Hz), 1.34−1.28 (m, 6H), 1.24 (t, 3H, J = 6.9 Hz), 1.01 (t, 3H, J = 6.9 Hz) ppm.…”

Section: -A M I N O -2 3 -D I M E T H O X Y -1 1 -M E T H Y L -1 2 -...mentioning

confidence: 99%

“…Column chromatography was carried out with silica gel grade 60 (0.040−0.063 mm) 230−400 mesh. The 1 H (500 MHz) NMR, 19 F (471 MHz) NMR, and 13 C{ 1 H} (126 MHz) NMR spectra were recorded on Bruker Avance Fourier transform NMR spectrometer (500 MHz). The 1 H (600 MHz) and 13 C{ 1 H} (151 MHz) NMR spectra were recorded on a Jeol JNM ECA Fourier transform NMR spectrometer (600 MHz) or Bruker Avance II Fourier transform NMR spectrometer (600 MHz).…”

Section: ■ Conclusionmentioning

confidence: 99%

“…The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.3c02133. Synthetic procedures for the preparation of all new compounds; NMR spectra of the synthesized products ( 1 H, 13 C{ 1 H}); 19 F NMR spectra for 4b-7b and 10b; 2D NMR spectra for compounds 4d; dynamic 1 H NMR spectra for 7d and 9d; and full data of X-ray diffraction analysis for compound 6b (PDF)…”

Section: Data Availability Statementmentioning

confidence: 99%

See 3 more Smart Citations

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

Miftyakhova,

Borisova,

Fakhrutdinov

et al. 2024

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

An easy synthesis of novel highly functionalized 5,6-dihydroindolo[2,1-a]isoquinolines was developed via a pseudo four-component domino reaction of 1-aroyl-3,4-dihydroisoquinolines, terminal α,β-ynones, and malononitrile. The selective formation of this biologically relevant heterocyclic core was achieved using a one-pot approach under microwave irradiation. The formation of the same skeleton through the reaction of 5,6-dihydropyrrolo[2,1-a]isoquinolines with malonic acid dinitrile supports the proposed mechanism, involving the intermediate product of the three-component reaction. Furthermore, the disproval of an alternative reaction pathway, which involved the dimerization of malononitrile followed by three-component transformation, was demonstrated. Introducing the malononitrile dimer as a CH acid resulted in the formation of a different pyrido[3′,4′:4,5]pyrrolo[2,1-a]isoquinoline core. Additionally, the synthesized 5,6-dihydroindolo[2,1-a]isoquinolines were examined for their photophysical properties, revealing their attractive luminescent characteristics.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: -A M I N O -2 3 -D I M E T H O X Y -1 1 -M E T H Y L -1 2 -...mentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

Section: Data Availability Statementmentioning

confidence: 99%

See 2 more Smart Citations

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

Miftyakhova,

Borisova,

Fakhrutdinov

et al. 2024

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, a microwave-assisted three-component domino metal-oxidizing agent-free reaction of 1-aroyl-3,4-dihydroisoquinolines 151 , terminal alkynes 170 , and cyclic NH-acids 171 (cyclic NH-amides and NH-azoles) in dry acetonitrile at 130 °C makes it possible to obtain quickly C-3- N -functionalized pyrrolo[2,1- a ]isoquinoline derivatives 172 . 79 On the other hand, metal-catalyzed reactions for preparing new functionalized pyrrolo[2,1- a ]isoquinolines are still relevant because it make easy the diversification of pyrroloisoquinoline skeleton…”

Section: Approach To the Synthesis And Diversification Of Isoquinolin...mentioning

confidence: 99%

Pyrrolo[2,1-a]isoquinoline scaffolds for developing anti-cancer agents

García Maza,

Salgado,

Kouznetsov

et al. 2024

RSC Adv.

View full text Add to dashboard Cite

show abstract

A single‐step synthesis of 5,6‐dihydropyrrolo[2,1‐a]isoquinolines and evaluation of their anti‐leukemic activity

Park,

Raikar,

Ahn

et al. 2024

Bulletin Korean Chem Soc

View full text Add to dashboard Cite

While a pharmaceutically intriguing scaffold, 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ), has precedently been prepared from diverse tetrahydroisoquinolines (THIQs) using elaborate conditions, convenient metal‐free methods were discovered from condensation of cyanomethylene‐THIQ (1) and α‐halo‐ketones or aldehydes (1a) to afford 15 DHPIQs (2–16) in moderate yields by employing unique reactivities of the secondary amine and α‐carbon to the nitrile of 1. Preliminary biological studies with chronic myelogenous leukemia K562 and adriamycin‐resistant K562 (K562/ADM) cells exhibited some of the DHPIQs tested were active in the both cell lines. In particular, cyclohexyl‐fused DHPIQ (10) showed GI50 values of 9.79 and 13.60 μM in K562 and K562/ADM cells, respectively. Based on the flow cytometry analysis of 10, the anti‐cancer activity could be from apoptosis‐related mechanisms. Overall, this DHPIQ scaffold may be further optimized to discover clinically meaningful anti‐leukemic agents overcoming adriamycin resistance.

show abstract

Three-component synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines from 1-aroyl-3,4-dihydroisoquinolines, electron-deficient alkynes and NH-acids

Cited by 9 publications

References 26 publications

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

Pyrrolo[2,1-a]isoquinoline scaffolds for developing anti-cancer agents

A single‐step synthesis of 5,6‐dihydropyrrolo[2,1‐a]isoquinolines and evaluation of their anti‐leukemic activity

Contact Info

Product

Resources

About