- Synthesis method of ulipristal acetate intermediate
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The invention provides a synthesis method of a ulipristal acetate intermediate. The synthesis method of the ulipristal acetate intermediate comprises the following steps: 1) a cyano reaction: dissolving a 3-ketal compound (I) in ethyl acetate, adding acetone cyanohydrin and triethylamine, and carrying out reacting to obtain a 17-cyanohydrin compound (II); 2) a protective reaction: adding dichloromethane, imidazole and a silanization reagent into a wet product of the 17-cyanohydrin compound (II), keeping the above raw materials at a temperature of 20-25 DEG C until the raw materials react completely so as to obtain a protected compound (III); 3) a methylation reaction: adding an ether solvent into a wet product of the protected compound (III), controlling a temperature to be -10 DEG C to 5DEG C, dropwise adding a lithium methide solution, carrying out a reaction with a temperature controlled to be -40 DEG C to 5 DEG C until the raw materials are completely reacted so as to obtain a methide (IV-1) solution; and 4) a ketalation reaction: adding ethylene glycol, triethyl orthoformate and p-toluenesulfonic acid (PTS) into the methide (IV-1) solution, and carrying out a heat-preserved reaction at a temperature of 20-25 DEG C until the raw materials are completely reacted so as to obtain a diketal (V).
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- Environmentally-friendly synthesis method of ulipristal acetate intermediate and ulipristal acetate
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The invention provides a method for environmentally-friendly synthesis of an ulipristal acetate intermediate and ulipristal acetate. According to the invention, a compound 2 is used as a starting rawmaterial, and reacts with acetylene in a solvent to form an alkynyl alcohol compound intermediate 3, a hydration reaction is performed with water under the catalysis of an ionic liquid and CO2 to obtain an intermediate 4, the intermediate 4 is subjected to carbonyl protection to obtain an intermediate 5, and the intermediate 5 is subjected to double bond epoxidation, a Grignard reaction, decarbonylation protection and acetylation to obtain the high-purity ulipristal acetate. The method is environment-friendly, convenient in steps, mild in conditions, low in cost, easy to amplify and suitable for industrial production, and the solvent can be recycled.
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- 20-ketofatty -11β-arylpropionic agonists or antagonists and having its deriv. nonsteroid antiandrogenic characteristics
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The invention is directed to a novel class of steroids which exhibit potent antiprogestational activity.
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- INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17α-ACETOXY-11β-[4-(N,N-DIMETHYL-AMINO)- PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS
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The present invention relates to a new industrial process for the synthesis of solvate- free 17α-acetoxy-11β-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB -2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method, ii) the obtained 3-(ethylene-dioxy)-17α-ethynyl-17β-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid, iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, then v) the obtained 3-(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11l)-diene-20- one of formula (VI) is reacted with ethylene glycol hi dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-19-norpregna- 5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5α,10α- and 5β,10β-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran in the presence of copper(I) chloride catalyst without separation of the isomers by known method, viii) the obtained 3,3,20,20-bis(ethylene-dioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norpregn-9(11)-ene of formula (III) is reacted with potassium hydrogensulfate in water by known method, ix) the obtained 11β-[4-(N,N-dimethylamino)-phenyl]-17α-hydroxy-19-norpregn-4,9-diene-3,20-dione of formula (II) is acetylated with acetic anhydride in the presence of perchloric acid by known method, finally x) the solvate-free compound of formula (I) is liberated from the obtained solvate containing compound of formula (I) in a 1 : 1 mixture of ethanol and water at 70° C.
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Page/Page column 9; 13
(2008/06/13)
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- 17β-acyl-17α-propynyl-11β-(cyclic amino) aryl steroids and their derivatives having antagonist hormonal properties
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The invention is directed to a novel class of 17β-acyl-17α-propynyl steroids which exhibit potent antiprogestational activity.
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Page/Page column 20
(2008/06/13)
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- 20-keto-11β-arylsteroids and their derivatives having agonist or antagonist hormonal properties
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The invention is directed to 20-keto-11 beta -arylsteroids of formula I: wherein R1, R6, R7, R9, R12 and X are as defined by the specification. The compounds exhibit progestational and antiprogestational activities.
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