PRODUCTION METHOD FOR ULIPRISTAL ACETATE AND ITS INTERMEDIATES Russian patent published in 2017 - IPC C07J41/00 C07J21/00 C07J75/00 A61K31/58 A61P15/18 

FIELD: biotechnology.

SUBSTANCE: invention relates to a method of producing ulipristal acetate which includes the following stages:

where R is a hydroxyl protective group isolated from -CH(CH₃)-OR₁, where R₁ is isolated from C₁-C₁₀ of alkyl and the dashed lines in formula V represent the double bonds in 5(10), 9(11) or 4(5), 9(10). The method also comprises of the following stages: a) use of 3.3-(ethylene dioxyl)-19-norpregn-5(10), 9(11)-diene-3.17-dione by formula II as the starting material and the use of spirits as the reaction solvent with cyan reagent to prepare the compound 3.3-(ethylene dioxy)-17β-cyano-7α-hydroxyl-19-norpregn-5(10), 9(11)-diene by formula III in a faintly acid medium at a temperature from -10°C to the room temperature; b) the production of the compound by formula IV via the reaction of the compound by formula III and hydroxyl protective group of the reagent in an acid medium in a solvent; c) interaction of the compound by formula IV with a methylating reagent and hydrolysis of compound by formula IV in an acid medium after a methylating reaction to obtain 5(10), 9(11)-diene-3.20-dione or 4(5), 9(10)-dienen-3.20-dione by formula V, or their mixture; d) interaction of the compound by formula V with ethylene glycol by the catalysis of p- toluenesulfonic acid and trimethyl orthoformate or triethyle orthoformate at the room temperature in dichloromethane with the yield of the compound 3.3-(ethylene-dioxy)-17α-hydroxy-19-norpregn-5(10), 9(11)-diene by formula VI; e) epoxidation of the compound in formula VI by hydrogen peroxide with the yield of the compound 3,3,20,20-bis (ethylene dioxyl)-17α-hydroxyl-5,10-epoxy-19-norpregn-9(11)-en by formula VII; f) additional reaction between the compound by formula VII and 4-(N, N-dimethyl amidogen) phenyl magnesium bromide of the Grignard reagent with the yield of the compound 3,3,20,20-bis(ethylene dioxy)-5α-17α-dihydroxy-11β--[4-(N,N-dimethylamino)-phenyl-]-19-norpregn-9(11)-en by formula VIII; g) the hydrolys of the compound by formula VIII in acid conditions with the production of 17α-hydroxy-11β-[4(N,N-dimethylamino)-phenyl-]-19-norpregn-9(11)-diene-3,20-dione by formula IX and h) the acetylation of the compound by formula IX with acetic acid, perchloric acid, acetic anhydride at a temperature of 0-10°C by dichloromethane with the production of the ulipristal acetate compound by formula I. The invention also relates to the compound by formula IV, to the method of production of the compound by formula IV, to the method of production of the compound by formula V.

EFFECT: new method proposed for producing ulipristal acetate with a high yield and high purity of the final product, applicable in the industrial production.

8 cl, 22 ex