DE1056603B - Process for the preparation of 19-nor-17-alpha-alkyltestosterones - Google Patents

Description

Process for the preparation of 19-nor-17-a-alkyltestosterones In the British patent specification 723 697 describes 17-cyanohydrins of sterols, which carry an OH group in position 3. However, these connections are not immediate can be used in therapy.

It has now been found that 17-cyanohydrins, which are a 3-ethoxy or have a 3-ethylenedioxy group, immediately after decomposition with acids d receives 4-3-ketones (i.e. e.g. the 17-a-methyl-19-nortestosterone) which immediately can be used as therapeutic products and in any case one of the known compounds have various therapeutic effects.

As starting materials for the production of this important class of If there is a high biological and therapeutic interest, preference is given to using the 3-derivatives of 17-cyanohydrin of 19-norandrostendione, which are described in the patent application R21120IVb / 12o are described, namely 3-ethoxy-17-cyan-17-ol-oestra-3,5-diene and 3-Ethylenedioxy-17-cyano-17-ol-oestr-5-en. If you have a solution of said cyanohydrin with an ethereal solution of an alkyl magnesium halide (where the alkyl group Has 1 to 4 carbon atoms and the halide is a bromide or iodide) converts, receives after decomposition of the excess alkyl magnesium halide with H Cl, the Process product, 19-nor-17a-alkyltestosterone. This is how you get that 19-nor-17a-methyltestosterone, melting point 156 to 157 ° C, 19-nor-17a-ethyltestosterone, Melting point 140 to 141'C, the 19-nor-17a-propyltestosterone, melting point 121 to 122 ° C, 19-nor-17a-butyltestosterone, melting point 128 ° C.

Example 1 For the solution of 10 parts of 3-ethoxy-17-cyano-17-oloestra-3,5-diene 35 parts of methyl magnesium bromide are added to 150 parts of anhydrous benzene in 200 parts Add anhydrous ether to part. The mixture is refluxed for 2 hours in a nitrogen atmosphere boiled, then poured onto ice and acidified with 50% hydrochloric acid. After 1 to Separation is carried out for 2 hours at room temperature in a nitrogen atmosphere and under constant pressure Stirring the solvent; the aqueous layer is washed with a benzene-ether mixture (1: 1) extracted several times and the collected benzene ethereal solutions are washed neutral with water, dried with Na2S04 and evaporated to dryness in vacuo. The crystalline residue is taken up with an ether-hexane mixture (2: 1), digested by boiling at reflux temperature, cooled in the refrigerator and filtered off with suction. 8.3 parts of 17a-methyl-19-nor-testosterone, which melts at 152 to 155 ° C., are obtained.

@, mäk ° '`` °' at 240 m # t: 10 log s = 4.2.

By redissolving the melting point increases to 156 to 157 ° C. Yield: 940 / ,. Example 2 The procedure is as in Example 1, but with 3-ethylenedioxy-17-cyan-17-ol-oestr-5-ene instead of 3-ethoxy-17-cyan-17-ol-oestra-3,5-diene. Yield: 950/0.

Example 3 A solution of 10 parts of 3-ethylenedioxy-17-cyan-17-ol-oestr-5-ene 50 parts of ethylmagnesium iodide are added to 150 parts of anhydrous benzene in 200 parts Allocate anhydrous ether; the mixture was placed in a nitrogen atmosphere for 3 hours Heated to reflux, then poured into ice and acidified with 50% hydrochloric acid. After 2 hours, separation is carried out at room temperature in a nitrogen atmosphere and under constant pressure Stir the solvent off; the aqueous layer is washed with a benzene-ether mixture (1: 1) extracted several times and the combined benzene-ethereal solutions are Washed neutral with water, dried with Nag S 04 and im. Vacuum to dryness evaporated. The residue is recrystallized from methanol. The 17a-ethyl-19-nor-testosterone is obtained with a melting point of 140 to 141 ° C.

2 @ a '' ° "°` at 240 mp.: 10 log a = 4.2. Yield: 60%. example .4- ..

The procedure is as in Example 3 by adding 3-ethoxy-17-cyan-17-ol-oestra-3,5-diene used instead of 3-ethylenediocyanate-17-cyan-ol-oestr-5-en. Yield: 55%.

Claims (1)

PATENT CLAIM: 1. Process for the preparation of 19-nor-17a-alkyltestosterones, characterized in that a 3-derivative of 17-cyanohydrin of 19-nor-androstenedione, in particular 3-ethoxy-17-cyan-17-oloestra- 3,5-diene or 3-ethylenedioxy-17-cyano-f7 = ol-oestr-5 = en is reacted in a known manner with excess alkyl magnesium halide and the reaction mixture is then decomposed with HCl. 2.- The method according to claim 1, characterized in that an alkyl magnesium halide whose alkyl radical contains 1 to 4 carbon atoms is used. Documents considered: German Patent No. 931769. Journ. Amer. Chem. Soc., 76, p. 4092 (1954).