New 4-imino-4H-Chromeno[2,3-d]Pyrimidin-3(5H)-Amine: Synthesis, Cytotoxic Effects on Tumoral Cell Lines and in Silico ADMET Properties

The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.

Synthesis and fungicidal activity of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines

A number of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines were synthesized. The structures of these new compounds were confirmed by ^1H NMR, IR and elemental analysis. Biological evaluation in the greenhouse showed several compounds have good fungicidal activities at 25 mg/L.

Synthesis, Crystal Structure and Antitumor Activity of (E)-4-tert-Butyl-N-(2,4-dichlorobenzylidene)-5-(1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound （E）-4-tert-butyl-N-（2,4-dichlorobenzylidene）-5-（1,2,4-triazol-1-yl）-thiazol-2-amine was synthesized by the reaction of 4-tert-butyl-5-（1,2,4-triazol-1-yl）-thiazol-2-amine with 2,4-dichlorobenzaldehyde, and its crystal structure was determined by singlecrystal X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a = 7.9748（4）, b = 10.1803（5）, c = 11.4603（6）, α = 102.882（1）, β = 100.253（1）, γ = 104.457（1）°, V = 850.95（7）3, Z = 2, F（000） = 392, C16H15Cl2N5S, Mr = 380.29, Dc = 1.484 g/cm3, S = 1.095, μ = 0.512 mm-1, the final R = 0.0301 and wR = 0.0965 for 3334 observed reflections （I 〉 2σ（I））. The preliminary antitumor activity shows that for the title compound the IC50 of Hela is 0.175 μmol/mL and that of Bel7402 is 0.156 μmol/mL.

Synthesis, Crystal Structure and Antitumor Activity of 4-tert-Butyl-N-(2-fluorophenyl)-5- (1H-1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound has been synthesized by the reaction of 1-bromo-3,3-dime- thyl- 1 - （1 H- 1,2,4-triazol- 1 -yl）butan-2-one with 1 -（2-fluorophenyl）thiourea, and its crystal struc- ture was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with a = 15.2568（6）, b = 12.1533（5）, c = 16.7307（7） A, Z = 8, V = 3102.2（2） A3, Mr = 317.39, Dc = 1.359 g/cm3, S = 1.05, μ = 0.223 mm-1, F（000） = 1328, the final R = 0.034 and wR = 0.097 for 2590 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intramolecular N-H…N hydrogen bond, which plays an important role in stabilizing the crystal structure. In addition, the preliminary biological test on the title compound shows good antitumor activity, with IC50 of 0.122 μmol/mL against the Hela cell line.

Synthesis, Crystal Structure and Antitumor Activity of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-3,5-diiodinebenzyl)-thiazol-2-amine

The title compound, 4-（tert-butyl）-5-（1 H- 1,2,4-triazol- 1 -yl）-N-（2-hydroxy-3,5-diio- dinebenzyl）thiazol-2-amine, was synthesized via the reduction of 4-（tert-butyl）-5-（1H-l,2,4- triazol-l-yl）-N-benzylidene-thiazol-2-amine with NaBH4, and its crystal structure was determined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic system, space group P21/c with a = 7.91944（19）, b = 10.5250（3）, c = 24.4985（6） A, Z = 4, V = 2041.66（9） A3, Mr = 599.22, Dc = 1,949 Mg/m3, S = 1.120, p = 3.203 mm-1, F（000） = 1152, the final R = 0.0283 and wR = 0.0592 for 3490 observed reflections （I 〉 2σ（I））. X-ray analysis displays that the crystal water takes part in three intermolecular hydrogen bonds of O（2）-H（2A）…O（1）, O（2）-H（2B）…N（I） and N（5）-H（5）…O（2）, and an octatomic ring R^（8） is formed via intramolecular hydrogen bond of O（I）-H（IA）…N（4）. Furthermore, the I…I contacts are involved in stabilizing the overall three-dimensional network structure. The preliminary biological test shows the title compound has good antitumor activity with the IC50 value of 26 μM against the Hela cell line.

Synthesis of Racemic Bis[2-(6-fluoro-2-chromanyl)-2-hydroxyethyl]-amine Methanesulfonic Acid Salt Using Lithium Aluminum Amide as a Promoter in Regioselective Ring Opening of Epoxide

Lithium aluminium amide [LiAI（NHR）4] 5 obtained by treating the primary amine 4 with LiAlH4 could promote the ring opening of epoxide 2 and led to high regioselective product of racemic bis[2-（6-fluoro-2-chromanyl）-2-hydroxyethyl]amine methanesulfonic acid salt 7.

Facile Synthesis of [1,2,4]Triazolo[4,3-a]pyrazin-3-amines via Oxidative Cyclization of 1-(Pyrazin-2-yl)guanidine Derivatives

In this study, we applied a novel, mild, and convenient synthetic method involving the oxidative cyclization of 1-(pyrazin-2-yl)guanidine derivatives to produce [1,2,4]triazolo[4,3-a ]pyrazin-3-amines. We optimized the reaction procedure to easily obtain 5-chloro-[1,2,4]triazolo[4,3-a ]pyrazin-3-amine. Various types of halogenated pyrazines can successfully undergo this process. We synthesized a series of 1-(pyrazin-2-yl)guanidines and [1,2,4]triazolo[4,3-a ]pyrazin-3-amines, and then elucidated their structures based on their ~1H-NMR, ^(13)C-NMR, ESI-HRMS, and nuclear Overhauser effect spectra.

4-(7-Methoxy-2,2-dimethyl-2,3-dihydrobenzo-furan-5-yl)-N-(pyridin-2-yl)thiazol-2-amine: Chiral Crystal from Achiral Molecule

The title compound 4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N- （pyridin-2-yl） thiazol-2-amine was synthesized by reacting 2-bromo-1-（7-methoxy-2,2-dime- thyl-2,3-dihydrobenzofuran-5-yl）ethanone with 1-（pyridine-2-yl）thiourea, and its crystal was determined by single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, chiral space group C2 with a = 18.1328（14）, b = 5.5969（5）, c = 19.2195（15） A, β= 115.5420（10）°, V= 1759.9（2）A3, Z = 4, F（000） = 744, C19H19N3O2S, Mr= 353.43, Dc= 1.334 g/cm3, S = 1.15, μ = 0.201 mm-1, the final R = 0.035 and wR = 0.111 for 2307 observed reflections （I 〉 2σ（I））. The Flack parameter is -0.03（10）. The preliminary bioassay result indicated that the title compound exhibits strong insecticidal activity （93.75% mortality） against Mythimna separate at the concentration of 1.000 g/L.

Synthesis and Crystal Structure of N-((6-chloropyridin-3-yl)methyl)-6-ethoxy-N-ethyl-3-nitropyridin-2-amine

The title compound N-（（6-chloropyridin-3-yl）methyl）-6-ethoxy-N-ethyl-3-nitropyri-din-2-amine（4） was synthesized by reacting the mixture of 6-chloro-2-ethoxy-3-nitropyridine（1） and 2-chloro-6-ethoxy-3-nitropyridine（2） with 3,and its structure was determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P21/n with a = 7.3441（2）,b = 9.9041（3）,c = 11.7368（3） ,α = 101.410（2）,β = 102.1340（10）,γ = 99.594（2）o,μ = 0.260 mm^-1,Mr = 336.78,V = 798.58（4）（A°）^3,Z = 2,Dc = 1.401g/cm^3,F（000） = 352,T = 296（2） K,R = 0.0210 and wR = 0.1053.

Synthesis and Structural Characterization of Di(2-amino-5-methyl-1,8-naphthyridin-1-ium-7-carboxylato)dichlorocuprate(Ⅱ) Dihydrate

Di（2-amino-5-methyl-1,8-naphthyridin-1-ium-7-carboxylato）dichlorocuprate（Ⅱ） di- hydrate has been prepared from 5,7-dimethyl-1,8-naphthyridine-2-amine, CuCl2·2H2O and concentrated hydrochloride acid, and its structure was determined by X-ray diffraction at 298 K. The compound （C20H22Cl2CuN6O6, Mr = 576.88） crystallizes in monoclinic, space group P21/n with a = 9.102（9）, b = 12.150（12）, c = 10.619（10） A,β = 91.20°, V= 1174.1（19） A^3, Z= 2, Dc= 1.632 g/cm^3, F（000） = 590,μ = 1.208 mm^-1, R = 0.0392 and wR = 0.0984. The Cu^2＋ ion is six-coordinated by two nitrogen and two oxygen atoms from two different naphthyridine ligands at the equatorial positions together with two chloride ions located at the axial positions.

Novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives as dual-action hypoglycemic agents that activate GK and PPARc

A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARg.When given orally to normal mice,the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.

Synthesis and Crystal Structure of N_3-(Dimethyl-pyrimidine)-N_4-(tri-O-acetyl-xylosyl) Thiourea

The crystal structure of the title compound （C18H24N4O7S, Mr = 440.47） was prepared by the condensation of 2,3,4-tri-O-acetyl-β-D-xylopyranosyl isothiocyanate with 4,6-dimethylpyrimidin-2-amine and structurally determined by single-crystal X-ray diffraction. The crystal belongs to the monochnic system, space group P2 1 with a = 7.5500（17）, b = 10.498（2）, c = 14.208（3） A, β = 99.929（4）°, V = 1109.2（4） A^3, Z = 2, Dc = 1.319 g/cm^3,μ = 0.191, F（000） = 464, Flack = 0.00（15）, R = 0.0684 and wR = 0.1103. In the crystal structure, the xylose ring adopts a ^4C1 chair conformation. Due to the hydrogen bonding interaction between N（4）-H（4A） and N（1）, the pyrimidine ring is well positioned.

New method in synthesizing an optical active intermediate for (R,R)-formoterol

（R）-1-（4-Methoxyphenyl）propan-2-amine 2a, an optical active intermediate for （R,R）-formoterol, was synthesized from Dalanine in 65% overall yield by using a simple route, which contained protecting amino group, cyclization, coupling with Grignard reagent, reduction and deprotection.

Cu（OAc）2/Pyrimidines-Catalyzed Cross-coupling Reactions of Aryl Iodides and Activated Aryl Bromides with Alkynes under Aerobic, Solvent-free and Palladium-free Conditions

Excellent results have been achieved in the Cu（OAc）2-catalyzed Sonogashira cross-couplings of aryl iodides and activated aryl bromides utilizing TBAF （tetrabutylammonium fluoride） as the base and 4,6-dimethoxypyrimidin-2-amine as the ligand. It is noteworthy that the reaction is conducted under aerobic, solvent-free and palladium-free conditions.

One-pot synthesis of acenaphtho[l,2-b]furan derivatives

New 9-（alkyl or aryl）acenaphtho[l,2-b]furan-8-（alky or aryl）amine compounds has herein been reported by one-pot reaction of （acenaphthylen-l-yloxy）trimethylsilane,alkyl and aryl aldehydes,and aryl and alky isocyanides in refluxing DMF.

Heterocyclization of thiocarbonohydrazides:Facile synthesis of 5-unsubstituted-1,3,4-thiadiazoles

2-（Hydrazinecarbothioyl）-N-substituted hydrazinecarbothioamides react with 2,3,5,6-tetrachloro-1,4-benzoquinone in high yields in a novel fast and facile method to give 5-unsubstituted-1,3,4-thiadiazole-2-amine derivatives.The synthesized compounds were characterized by spectroscopic methods and confirmed by using X-ray crystallography.A rationale for the formation of the products is presented.