Imidoyl Radicals for the Synthesis of Chromenoquinolines and Naphthyridines

The stability of imidoyl radicals prepared from 2-(2-alkenyloxy)-phenyl selenoimidates and 2-(2-allylamino)-phenyl selenoimidates and their intramolecular free radical cyclization through the slow addition of tri-N-butyltin hydride and AIBN to obtain 4-chromanones and 4-quinolones were studied. The extension of the methodology to N-phenyl substituted imidoyl selenoates produced tandem cyclizations of the imidoyl radical with the allyl substituent, followed for a second cyclization of the intermediate radical with the aromatic substituent to produce dihydro-chromenoquinolines or tetrahy-dro-dibenzonaphtyridines. Further oxidation with DDQ produced: 6H-chromeno [4,3,b] quinoline and 7-methyl-6H-chromenoquinoline from 2-alkenylamino-phenylbenzamide and 5,6-dihydro-dibenzo [b,h][1,6] naphthyridine and 5,6-dihydro-7-methyl-dibenzo [b,h][1,6] naphthyridine from 2-2-(alkylamino)-N-phenylbenzamides. The cyclization of 2-(N,N-di-prop-2.enylamino)-N-phenylnicotinamide selenoate obtained from 2-aminonicotinic acid, produced 5,6-dihidro-benzo[b]pyrido2,3-h] [1,6] naphthyridine.

Pd(OAc)2 catalyzed synthesis of heteroaryl-substituted 1,8-naphthyridine derivatives via C-N-coupling reactions of chloronaphthyridines

An efficient route to synthesize the heteroaryl-substituted 1,8-naphthyridine derivatives was described. Eight 2-heteroaryl- and 2,7-diheteroaryl-1,8-naphthyridine derivatives were obtained through palladium-catalyzed C-N-coupling reactions of chloronaphthyridines with imidazole, benzimidazole, morpholine, 3,5-dimethylpyrazole, and phthalimide in moderate to good yields.

Reactions of Naphthyridines with Aldehydes： Novel Derivatives with Red-Fluorescence Emissions and Two-Photon Absorptions

Four new 1,8-naphthyridine derivatives were synthesized by reacting the parent molecules with aldehydes and characterized. Two of the compounds have completely new and unusual skeletons, and display red-fluorescence emissions and two-photon absorption. Their structures were determined using MS, 1D and 2D NMR, and density functional theory calculations. The structural investigations of 2-methyl-l,8-naphthyridine hydrochloride and hydrobromide showed that abundant hydrogen-bonds and π-π interactions lead to extended networks.

Synthesis,Crystal Structure and Antitumor Activities of(14S)-2,14-diphenyl-6,6a,11,12-tetrahydro-5H,10H,14H-[1,8]naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile

The title compound（14 S）-2,14-diphenyl-6,6 a,11,12-tetrahydro-5 H,10 H,14 H-[1,8] naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile（C31 H26 N4, Mr = 454.56） has been synthesized with 2-aminonicotinaldehyde and 3-oxo-3-phenylpropanenitrile as starting materials, and its crystal structure was determined by single-crystal X-ray diffraction for the first time. The crystal belongs to the triclinic system, space group P1 with a = 8.5833（8）, b = 11.9168（12）, c = 14.4424（14） ？, α = 84.208（3）o, β = 88.427（3）o, γ = 73.704（3）o, V = 1410.7（2） ？3, Z = 2, F（000） = 480, μ = 0.064 mm–1, S = 0.966, the final R = 0.0484 and wR = 0.1388 for 5041 observed reflections with I 〉 2s（I） and 316 variable parameters. The preliminary biological tests show that the title compound has a good antitumor activity against K562 in vitro.

Synthesis,Crystal Structure and Biological Activity of 8-((4-((2,3-diaminopyridin-4-yl)oxy)-3-fluorophenyl)-amino)-2-(4-fluorophenyl)-3-methyl-2,7-naphthyridin-1(2H)-one

The new title compound 8-（（4-（（2,3-diaminopyridin-4-yl）-oxy）-3-fluorophenyl）-amino）-2-（4-fluorophenyl）-3-methyl-2,7-naphthyridin-1（2H）-one（C26H20F2N6O2, Mr = 486.48） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 15.365（3）, b = 13.144（2）, c = 11.863（2）, β= 108.882（3）°, Z = 4, V = 2267.0（7）3, Dc = 1.425 g/cm3, F（000） = 1008, μ = 0.105 mm-1, MoKa radiation（λ = 0.71073）, R = 0.0480 and wR = 0.1294 for 3197 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that the region C（substituents of 8-amino group and 3-methyl group on the 2,7-naphthyridin-1（2H）-one ring） of compound 6 are effectively planar. Intramolecular and intermolecular hydrogen bonds together with π···π interations are found in the structure. In addition, compound 6 shows potent c-Met and c-Kit kinase inhibition activities.

An efficient synthesis of 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles

Ethyl α-（dimethylaminomethylene）-2-cyanomethyl-4-phenylquinoline-3-carboxylate（2） as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate（1） and N,N-dimethylformamide dimethyl acetal（DMFDMA）.Reaction of this enamine with primary amines（3） in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives（4） in good yields by a tandem addition-elimination-cyclization reaction.

Synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3-e][1,6]naphthyridine-8-ones via Pictet–Spengler cyclization

An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′：5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet-Spengler cyclization is reported. The reaction of 4-（3-aminopyrimido[4,5-d]thieno-2-yl）quinoline-2-ones, which could be obtained from Thorpe-Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF3·OEt2 gives pyrimidothieno[1,6]naphthyridines in good yields.

Rigid chelating dicarbene ligands based on naphthyridine-fused bisimidazolium salts

Naphthyridine-fused bisimidazolium salts were designed and synthesized for the first time. The study of the Cu(Ⅱ) and Pd(Ⅱ) complexes demonstrated that the deprotonated dicarbene ligands are rigid chelating C,C-ligands with strong electron-donating ability in analogy with the classic phenanthroline N,N-ligands.