Richter Gedeon Nyrt.

Richter Gedeon Vegyeszeti Gyar Rt

Antal Aranyi

Sándor Mahó

Gábor Balogh

Zoltan Tuba

János Csörgei

Csaba Sánta

János Horváth

Zoltán Tuba

József Bódi

Zoltán Béni

László Terdy

Judit Horváth

Béla Sörös

György Visky

Csaba Molnár

György Gálik

Lajosné Dancsi

János Széles

Zoltán Horváth

Gyorgy Galik

Bela Soros

Judit Horvath

Janos Horvath

Zoltan Beni

Lajosne Dancsi

Zoltan Horvath

Laszlo Terdy

Janos Csorgei

Jozsef Bodi

The present invention relates to a new process for the synthesis of compounds of formula (I) (wherein the meaning of R is dimethylamino or acetyl group) using the compound of formula (II) (wherein the meaning of R is dimethylamino or 2-methyl-1,3-dioxolan-2-yl group) as starting material, as well as to the intermediate of the process. 

Industrial process for the synthesis of ulipristal acetate and its 4'-acetyl analogue

The invention relates to a new process for the synthesis of high purity 17&#x3b1;-cyanomethyl-17&#x3b2;-hydroxy-estra-4,9-diene-3-one (further on dienogest) of formula (I) from 3-methoxy-17-hydroxy-estra-2,5(10)-diene of formula (V). The invention relates also to the high purity 17&#x3b1;-cyanomethyl-17&#x3b2;-hydroxy-estra-4,9-diene-3-one and pharmaceutical compositions containing that as active ingredient. The pharmaceutical compositions according to this invention contain high purity dienogest of formula (I) in which the total amount of impurities is less than 0.1%, while the amount of 4-bromo-dienogest is under the detection limit (0.02%) as active ingredient or at least one of the active ingredients and auxiliary materials, which are commonly used in practice, such as carriers, excipients or diluents. According to our invention the dienogest of formula (I) is synthesized the following way: i) 3-methoxy-17-hydroxy-estra-2,5(10)-diene of formula (V) is reacted with aluminum isopropylate in the presence of cyclohexanone in an inert organic solvent under heating; ii) the so obtained 3-methoxy-estra-2,5(10)-diene-17-one of formula (IV) is reacted with cyanomethyl lithium at a temperature between 0 and &#x2212;30&#xb0; C.; iii) the obtained 3-methoxy-17&#x3b1;-cyanomethyl-17&#x3b2;-hydroxy-estra-2,5(10)-diene of formula (III) is reacted with a strong organic acid in tetrahydrofuran solution; iv) the obtained 17&#x3b1;-cyanomethyl-17&#x3b2;-hydroxy-estr-5(10)-ene-3-one of formula (II) is reacted with 1-1.5 equivalent of pyridinium tribromide in pyridine solution at a temperature between 0 and 60&#xb0; C., then the obtained crude dienogest of formula (I) is purified by recrystallization and preparative HPLC. 

High purity 17&#x3b1;-cyanomethyl-17&#x3b2;-hydroxy-estra-4,9-diene-3-one and process for the synthesis thereof

The invention relates to an industrial process for the preparation of 17-hydroxy-6&#x3b2;,7&#x3b2;;15&#x3b2;,16&#x3b2;-bismethylene-3-oxo-17&#x3b1;-pregn-4-ene-21-carboxylic acid &#x3b3;-lactone of formula (I), and to the key-intermediates for this process. 

Industrial process for the preparation of 17-hydroxy-6beta,7beta;15beta, 16beta-bismethylene-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid y-lactone and key intermediates for this process

The present invention relates to a process for the synthesis of the 17-acetoxy-11&#x3b2;-[4-(dimethylamino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione of formula (I): from 3,3-[1,2-etandiyl-bis(oxy)]-oestr-5(10),9(11)-dien-17-one of formula (II): 

Industrial method for the synthesis of 17-acetoxy-11&#x3b2;[4-(dimethylamino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione and the key intermediates of the process

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Érd, Hungary

Antal Aranyi