Synthesis of 4-alkyl-4H-benzo[e]- and 4H-pyrido[2,3-e]-1,2,4-triazin-3-one 1-oxides for potential anticancer activity

Alkylation of the sodium salt of 4H-benzo[e]-1,2,4-triazin-3-one 1-oxide and its 7-methyl homolog with benzyl bromide and chloromethoxyethyl acetate gave the 4-substituted products. Alkylation with aceto-bromoglucose formed the 3-ether. Alkylation of 4H-pyrido[2,3-e]-1,2,4-triazin-3-one 1-oxide gave the 4-substi-tuted products with both benzyl bromide and acetobromoglucose. Deacetylation of both the tetra-O-acetyl-glucosyl and acetoxyethoxymethyl derivatives was accompolished was accompolished. Antileukemia tests for several of the 4-alkyl derivatives showed no activity.     

Synthesis of thieno[2,3-e]-1,2,4-triazines

3-Methylmercapto-5-oxo-6-vinyl- and 2-methyl-3-mercapto-5-oxo-6-vinyl-2,5-dihydro-1,2,4-triazines were readily converted into the corresponding thieno[2,3-e]-1,2,4-triazine in one step by the action of phosphorus pentasulfide in pyridine. 4-Methyl-3-mercapto-5-oxo-4,5-dihydro-1,2,4-triazine is only converted into the 5-thioxo analog and no thiophene ring product was obtained under the same conditions. Thieno[2,3-e]-1,2,4-triazines were also more efficiently obtained by the action of phosphorus petnasulfide in pyridine on the appropriate 6-acylmethyl-3-mercapto-5-oxo-2,5-dihydro-1,2,4-triazine.     

3-Phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones and 2-Phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-ones

Condensation of 2,3-diaminopyridine ( 1 ) with ethyl o-, m- and p-substituted benzoylpyruvates 2–9 gave two isomeric products. The preferential formation of one or the other isomer has been achieved by different reaction conditions. All the products appear to exist in the enamine form as evidenced by their ¹H nmr and ir spectra.     

Synthesis of some pyrazolo[4,3-e][1,2]- and thiazolo[4,5-e][1,2]thiazine 1,1-dioxide derivatives

The synthesis of various 2-methylpyrazolo[4,3-e]- and thiazolo[4,5-e][1,2]thiazine 1,1-dioxide derivatives is described.     

Reactivity of 4-amino-6,7-diphenyl-8H-pyrazino[2,3-c]-1,2,6-thiadiazine 2,2-dioxide towards methylating agents

Reaction of the title compound with different methylating agents to give mono-, di- and trisubstituted derivatives has been studied.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

1,2,4-Triazines VIII. The synthesis of 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazines and 1,2,4-triazino[4,3-e]pyrazolo[],5-a] -1,3,5-triaziness

Substituted 2,5-dihydro-3[3-methyI(or phenyl)-5-aminopyrazolyl]-1,2,4-triazin-5-ones reacted with orthoesters to yield exclusively 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazin-5-ones. The structure elucidation was supported by independent synthesis of the isomeric 1,2,3-triazino-[4,3-e]pyrazolo[1,5-α]-1,3,5-triazin-7-one as well as by spectroscopical methods.