Preparation of Polyfunctional Naphthyridines by Cobalt-Catalyzed Cross-Couplings of Halogenated Naphthyridines with Magnesium and Zinc Organometallics

Abstract

CoCl (5%) catalyzes cross-couplings of various halogenated naphthyridines with alkyl- and arylmagnesium halides. Also, arylzinc halides undergo smooth cross-couplings with various naphthyridines in the presence of CoCl·2LiCl (5%) and sodium formate (50%), leading to polyfunctional arylated naphthyridines. Two of these arylated naphthyridines are highly fluorescent, with quantum efficiencies reaching 95% and long excited-state lifetimes of up to 12 ns.

Recent Progress in Utilization of Functionalized Organometallic Reagents in Cross Coupling Reactions and Nucleophilic Additions

“…Greiner and Knochel et al 10 reported an efficient synthesis of novel polyfunctionalized arylated naphthyridines by Co-catalyzed cross couplings between various halogenated naphthyridines and arylzinc halides, which offered the desired polyfunctional arylated naphthyridines in moderate to good yields (Scheme 6). The upsides of this protocol were that it was also suitable for the reaction of the arylmagnesium with various halogenated naphthyridines.…”

Discovery of 8-Amino-Substituted 2-Phenyl-2,7-Naphthyridinone Derivatives as New c-Kit/VEGFR-2 Kinase Inhibitors

“…All reactions involving air-or moisture-sensitive reagents were performed under a nitrogen or argon atmosphere. 1 HNMR spectra (400 MHz) and 13 CNMR (100 MHz) spectra were recorded on a Bruker BioSpin AG (Ultrashield Plus AV 400, Fällanden, Switzerland) spectrometer as deuterochloroform (CDCl 3 ) or dimethyl sulfoxide-d 6 (DMSO-d 6 ) solutions using tetramethylsilane (TMS) as an internal standard (δ = 0) unless noted otherwise. MS spectra were obtained on an Agilent technologies 6120 quadrupole LC/MS (ESI).…”

“…HPLC purity: 98.3%. 1 3-methyl-2-phenyl-8-((pyridin-3-ylmethyl)amino)-2,7-naphthyridin-1(2H)-one (10f): Yellow solid (78% yield). HPLC purity: 97.9%.…”

“…N-Heterocyclic scaffolds are ubiquitous building blocks that are used for pharmaceuticals and agrochemicals and in materials science. Novel ring structures may exhibit unique biological or physical properties [1]. Naphthyridines, which act as bioisosteres of quinolone, universally exist in nature and form an important class of nitrogen-containing heterocyclic compounds [2].…”

“…H NMR (400 MHz, DMSO-d 6 ) δ: 9.55 (t, J = 4.8 Hz, 1H), 8.55 (m, 1H), 8.43 (m, 1H), 8.08 (d, J = 4.4 Hz, 1H), 7.72-7.31 (m, 7H), 6.59 (d, J = 4.4 Hz, 1H), 6.48 (s, 1H), 4.68 (d, J = 4.8 Hz, 2H), 1.92 (s, 3H); 13 C NMR (100 MHz, DMSO-d 6 ) δ: 163.44, 158.12, 150.60, 148.91, 147.97, 145.17, 144.80, 138.23, 135.38, 135.10, 129.39, 128.55, 123.45, 107.11, 104.24, 103.45, 41.35, 21.18; ESI-MS m/z: 343.4 ([M + H] + ).3-methyl-2-phenyl-8-((pyridin-4-ylmethyl)amino)-2,7-naphthyridin-1(2H)-one (10g): Yellow solid (67% yield). HPLC purity: 97.7% 1. H NMR (400 MHz, DMSO-d 6 ) δ: 9.60 (t, J = 5.6 Hz, 1H), 8.46 (d, J = 5.0 Hz, 2H), 8.04 (d, J = 5.6 Hz, 1H), 7.56-7.46 (m, 3H), 7.34 (m, 2H), 7.28 (d, J = 5.0 Hz, 2H), 6.59 (d, J = 5.6 Hz, 1H), 6.49 (s, 1H), 4.70 (d, J = 5.6 Hz, 2H), 1.93 (s, 3H); 13 C NMR (100 MHz, DMSO-d 6 ) δ: 163.47, 158.19, 150.55, 149.44, 149.17, 145.18, 144.85, 138.24, 129.40, 128.58, 126.56, 122.15, 107.23, 104.23, 103.51, 42.74, 21.19; ESI-MS m/z: 343.4 ([M + H] + ).3-methyl-2-phenyl-8-((quinolin-4-ylmethyl)amino)-2,7-naphthyridin-1(2H)-one (10h): Yellow solid (88% yield).…”