METHOD FOR THE PREPARATION OF 1-(2-PROPARGYL)-1H-NAPHTHO[2,3-d][1,2,3]TRIAZOLE-4,9-DIONE-4-OXIME-2-OXIDE Russian patent published in 2023 - IPC C07D249/22 A61K31/4192 A61P35/00 

FIELD: organic chemistry and medicine.

SUBSTANCE: invention relates to the field of organic chemistry and medicine and relates to a method for obtaining biologically active chemical compounds with cytotoxic activity. The method for obtaining 1-(2-propargyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione-4-oxime-2-oxide (I) is carried out according to the scheme, without purification of isolated intermediates, 4,9-dioxo-1-(2-propargyl)-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazole-2 is used as the starting material -oxide (V), while a five-fold molar excess of sodium nitrite is added to 2-propargylamino-3-chloro-1,4-naphthoquinone (II) in acetic acid in small portions for 1 h, the reaction mass is stirred for 30 minutes at 20-22°C, then diluted with ice water, yellow precipitate of 2-(N-nitrosopropargylamino)-3-chloro-1,4-naphthoquinone (III) is separated by filtration, washed with water, dried in the dark without further purification, dissolved in dimethyl sulfoxide (DMSO) and a solution of sodium azide is added in water, the reaction mass is stirred for 30 min at 30°C. The resulting azide (IV) is isolated by pouring into a tenfold volume of ice water, the precipitate of azide (IV) is filtered off, dissolved in benzene and boiled for 30 min, then the solution is concentrated, cooled to 20°C, precipitated 4,9-dioxo-1 -(2-propargyl)-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazole-2-oxide (V) is separated by filtration, washed with two portions of water, then with ethanol, dried. Then the resulting triazole oxide (V) is oximated with hydroxylamine hydrochloride during short-term boiling in pyridine:

EFFECT: obtaining a product with antiproliferative activity and retaining the possibility of additional functionalization, while the reactions are carried out without purification of the isolated intermediate products, which makes it possible to reduce the number of stages and achieve a high total yield of the target product.

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