Palladium-Mediated Synthesis of 2-([Biphenyl]-4-yloxy)quinolin-3-carbaldehydes through Suzuki–Miyaura Cross-Coupling and Their in Silico Breast Cancer Studies on the 3ERT Protein

Abstract

A series of novel quinoline appended biaryls have been synthesized (5a−5o) by reacting various substituted boronic acids (4e−4h) with various substituted 2-(4-bromophenoxy)quinolin-3-carbaldehydes (3a−3d) through carbon−carbon bond formation. Effects of various quinoline appended biaryls (5a−5o) on the breast cancer protein 3ERT are moderate to high, as found by in silico molecular docking studies. Comparatively, all quinoline appended biaryls (5a−5o) 5h show better efficacy with a binding energy of −9.39 kcal/mol, and hydrogen bonds are Thr347, Glu353, and Arg394 in the binding pocket. Conclusively, the final novel quinoline appended biaryls (5a−5o) have been confirmed with all the spectral studies, and their efficacy has been validated with in silico studies.

Synthesis, Characterization, In Silico DFT, Molecular Docking, and Dynamics Simulation Studies of Phenylhydrazono Phenoxyquinolones for Their Hypoglycemic Efficacy

“…The synthesis of phenylhydrazono phenoxyquinolines ( 5a – 5x ) is demonstrated in Scheme . Initially, the core nucleus 2-chloroquinoline was treated with various substituted phenolic compounds ( 2a – i ) in the presence of K 2 CO 3 in DMF at 100 °C for 1 h, which affords the desired substituted 2-phenoxyquinoline-3-carbaldehyde ( 3a – 3i ) . Subsequently, hydrazide Schiff’s bases [3-((2-(4-nitro/bromophenyl)­hydrazono)­methyl)-2-phenoxyquinolines ( 5a – 5x )] were synthesized by a catalytic amount of acetic acid using appropriate aldehyde ( 3a–3i) with substituted (4-bromo or nitro) phenyl hydrazine ( 4a – 4b ) in methanol at 65 °C for 30 min.…”

“…Initially, the core nucleus 2-chloroquinoline was treated with various substituted phenolic compounds ( 2a – i ) in the presence of K 2 CO 3 in DMF at 100 °C for 1 h, which affords the desired substituted 2-phenoxyquinoline-3-carbaldehyde ( 3a – 3i ). 21 Subsequently, hydrazide Schiff’s bases [3-((2-(4-nitro/bromophenyl)hydrazono)methyl)-2-phenoxyquinolines ( 5a – 5x )] were synthesized by a catalytic amount of acetic acid using appropriate aldehyde ( 3a–3i) with substituted (4-bromo or nitro) phenyl hydrazine ( 4a – 4b ) in methanol at 65 °C for 30 min. The 1 H nuclear magnetic resonance (NMR) spectrum of compound 3-((2-(4-nitrophenyl)hydrazono)methyl)-2-phenoxyquinoline ( 5a ) exhibited chemical shifts in the aromatic region ranging from δ 11.63 to 7.32–7.27 ppm.…”

Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-b]pyridines Prepared by Suzuki Cross Coupling

“…m.p. > 300 (20), 20 was prepared according to general procedure from 6 (0.100 g, 0.35 mmol) and (4-methoxyphenyl)boronic acid 9 (0.063 g, 0.42 mmol) in the presence of 0.032 g (0.03 mmol) of Pd(PPh 3 ) 4 and K 2 CO 3 (0.120 g, 0.87 mmol) as a base in mixture of solvents dioxane:water 3:1. Product was isolated in the form of white crystals 0.057 g (52%).…”

“…There is a substantial difference in the structural and electronic properties of palladium chemistry when compared with classic methods that include corresponding carbocyclic compounds. One of the most used methods for the direct formation of carbon-carbon bonds is Suzuki cross coupling from boronic acid and an organohalide, utilizing mostly different palladium(0) complexes as catalysts as well as a corresponding base in the synthesis of biologically active compounds [17][18][19][20][21]. The main advantage of this reaction is the commercial availability of various boronic acids that are less toxic and safer for the environment, as well as mild reaction conditions like using water [22] as a solvent.…”