1,2,4-triazines. 1. A convenient synthesis of 4,5-dihydro-1,2,4-triazin-3-(2H)one and its 6-substituted derivatives

A facile synthesis of 4,5-dihydro-1,2,4-triazin-3-(2H)one (2a) from 5-methylthio-1,2,4-triazin-3-(2H)one (1a) with sodium borohydride is described. The reaction provides a convenient method for its 6-substituted derivatives (2b-h).     

1,2,4-Triazines. II. A new general synthesis of 3,4-dihydro-1,2,4-triazin-5-(2H)ones

3,4-Dihydro-1,2,4-triazin-5-(2H)ones were prepared by the reduction of 3-methylthio-1,2,4-triazin-5-(2H)-ones with sodium borohydride in dimethylformamide. The synthesis appears to be general.     

Synthesis and structure of dihydro-1,2,4-triazin-6(1H) ones

Reactions of the iminoesters 3a-c with hydrazine or 1,2-dimethylhydrazine gave 4,5-dihydro- 4a-c or 2,5-dihydro-1,2,4-triazin-6(1H) ones 7a-c , respectively. When methylhydrazine was employed, 1-methyl-4, 5-dihydro- 5a-c and 2-methyl-2,5-dihydro-1,2,4-triazin-6(1H) ones 6a-c were obtained. Compounds 6a-c exist as zwitterions in the solid state and in polar aprotic solvents.     

Efficient solid-phase synthesis of 4,5-dihydro-1,2,4-triazin-6(1H)-ones

A new and easy protocol for the formation of substituted 4,5-dihydro-1,2,4-triazin-6(1H)-ones was developed on solid support. The heterocyclic compounds were formed by nucleophilic reaction of hydrazine on thioamide esters. As cyclization was concomitant with cleavage from the support, substituted 4,5-dihydrotriazinones were obtained in high purity.     

Efficient synthesis of 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones and 5-substituted-1,2,4-triazin-6-ones

Treatment of methyl α-(dimethylarninomethyleneamino)carboxylates 1 (from α-amino acids and dimethylformamide dimethylacetal) with hydrazine gives 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones 2 , which are smoothly dehydrogenated to 5-substituted-1,2,4-triazin-6-ones 3 with potassium permanganate in acetone/acetic acid.     

Direct introduction of heterocyclic residues into 1,2,4-triazin-5(2H)ones

3-Aryl-1,2,4-triazin-5(2H)-ones 1a-c react with indoles 2a-c in trifluoroacetic acid/chloroform or in boiling butanol or acetic acid to give 3-aryl-6-(indolyl-3)-1,6-dihydro-1,2,4-triazin-5(2H)-ones 3a-g . Oxidation of the dihydro-1,2,4-triazin-5(2H)-ones 3a-e afforded 6-(indolyl-3)-1,2,4-triazin-5(2H)-ones 4a-e , products of nucleophilic substitution of hydrogen in 1a-c . Refluxing 1b with N-methylpyrrote 5b in butanol for an extended time resulted in the formation of 3-(4-chlorophenyl)-6-(1-meuiylpyrrolyl-2)-1,2,4-triazin-5(2H)-one 4h. The reaction of 1a-c with indoles 2a-c , pyrroles 5a,b , 1,3-dimethyl-2-phenylpyrazol-4-one (8) and aminothiazoles 9a,b in acetic anhydride affords the 1-acetyl-3-aryl-6-hetaryl-1,6-dihydro-1,2,4-triazin-5(2H)-ones 6a-s . Reaction of 1a-c with N-methyl-pyrrole 5b in acetic anhydride gives beside the 1:1 addition products 6h-k also the 2:1 addition products 7a-c .     

Heterocycles from substituted amides. VII Oxazoles from 2-isocyanoacetamides

Certain heretofore unknown tertiary α-isocyanacetanilides 1 are reported for the first time, prepared by methods necessarily different from those employed to prepare the previously cited aliphatic α-isocyano-acetamides 2 . Like 2, 1 has been shown to readily undergo dialkylation with alkyl halides. Moreover, 1 also gives rise to oxazole and oxazoline derivatives upon reaction with acyl halides and aldehydes, respectively, resembling the similarly activated α-isocyano esters and sulfones. Further, in a demonstrable ring-chain tautomeric equilibration, apparently restricted to tertiary amides, 1 readily cyclizes, providing the only known synthesis of 5-amino-2,4-unsubstituted oxazoles 3 . In other examples 4-chloro and 4-alkyl-5-amino-oxazoles are produced. The materials and reactions are characterized, and compared with previous related studies.     

New synthesis of 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives through cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

Some 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetones or acetophenones 2 were easily prepared. These compounds reacted with hydrazine derivatives to give 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives 3 , 4 and 6 in good yields. With phenylhydrazine, the intermediate hydrazones 5 were obtained. Their conversion into triazinones necessitated the presence of sodium ethylate.     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).     

6-(4-取代苯基)-5-甲基-4,5二氢-3(2H)哒嗪酮化合物的合成及其抑制血小板聚集作用

血小板聚集在血栓形成中起着先导而关键的作用,而严重威胁人类生命健康的心脑血管疾病多数与血栓形成和血栓栓塞有着密切的联系[1]。二氢哒嗪酮类化合物对抑制血小板聚集有较强的药理活性,对二磷酸腺苷(ADP)、花生四烯酸(AA)、血小板活化因子(PAF)和胶原(Collagen)引起的血小板聚集均有抑制作用。深入研究二氢哒嗪酮类化合物的构效关系,以期寻找活性更强的抗血小板聚集药物,是开发新型心脑血管系统疾病药物的重要研究方向之一。本文设计合成了6-(4-取代苯基)-5-甲基-4,5二氢-3(2H)哒嗪酮类化合物[2,3,4],并进行了体外药理实验。1实验部…     

Synthesis of 4-(2-acetoxyethoxymethyl)-6-methyl-1,2,4-triazin-3(4H)-one 1-oxide as thymidine analogue

Alkylation of the sodium salt and the trimethyl silylated derivatives of 6-methyl-1,2,4-triazin-3(4H)-one 1-oxide with chloromethoxyethyl acetate, n-hexyl chloride and benzyl bromide gave the 4-substituted products. However, attempts to achieve the ring closure of N⁴-(2-acetoxyethoxymethyl)thiosemicarbazide with bicarbonyl compounds to the corresponding as-triazines under different reaction conditions was not possible without disruption of the acetoxyethoxymethyl moiety. Although the as-triazine nucleoside analog II did not show antileukemic activity, this and other 4-alkylated as-triazine 1-oxides revealed good growth inhibitory effects against a representative spectrum of microorganisms.     

Heterocyclic synthesis using nitrile imines. 6. Synthesis of some new substituted 4,5-dihydro-1H-1,2,4-triazoles

A new series of substituted 1,2,4-triazoles was synthesized from the cycloaddition reaction of alkanal and cycloalkanal hydrazones containing electron-withdrawing groups (MeCO, PhCO, and MeOCO) with appropriate hydrazonoyl halides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 392–398, March, 2007.     

The Reactions of 6-(tert-Butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with Carbonyl Compounds

The reaction of 6-(tert-butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with acetone and benzaldehyde yields the corresponding hydrazones. In the presence of thionyl chloride the benzaldehyde hydrazone is converted to 3-(tert-butyl)-6-phenyl-1,2,4-triazolo[4,3-b]-1,2,4-triazin-2(1H)-one and this can also be formed via the acylation of the starting hydrazinotriazinone using benzoyl chloride.