CH629826A5 - Steroids, process for preparing them and their use in the synthesis of tritium-labelled steroids - Google Patents

Description

The subject of the present invention is the new steroids of formula:

in which R represents hydrogen, an alkyl group having from 1 to 4 carbon atoms, or a tetrahydropyrannyl, trityl or trimethylsilyl radical, and Ri represents hydrogen, an acyl radical having from 1 to 5 carbon atoms or the tetrahydropyrannyl radical.

When R represents an alkyl group, it can be, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl.

When R 1 represents an acyl radical, it can be derived from formic, acetic, propionic, butyric or valeric acid.

Among the products of formula I, there may be mentioned in particular:

- dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 diol-3,20ç;

- dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 methoxy-3 ol-20 £;

- dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6-methoxy-3 acetoxy-20ç;

- dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 ol-3 acetoxy-20ç.

The products of general formula I are useful as starting materials for the synthesis of substituted steroid derivatives labeled with tritium.

The subject of the invention is also a process for preparing the products corresponding to general formula I above.

This process is characterized in that:

- subject to methylation at position 21, by means of a methyl halide, methyl-17a 19-nor-pregna-trien-1,3,5 (10) 3-methoxy-one-20,

- Acting, on dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 (10) methoxy-3 one-20 resulting, a reducing agent to obtain dimethyl-17a, 21 19-nor-pregnatrien-1,3 , 5 (10) 3-methoxy ol-20 £;

- subjects the latter to the action of lithium in ammonia according to the Birch reaction;

- isomerizes dimethyl-17a, 21 19-nor-pregnen-5 (10) oI-20Ç one-3 obtained, by means of a strong acid, into dimethyl-1 7a, 21 19-nor-pregnen-4 ol- 20ç one-3;

- subject the latter to the action of an esterification or etherification agent;

- faitagirsurlediméthyl-17a, 21 19-nor-pregnen-4 Ri0-20ç one-3 resulting, Ri having the abovementioned meanings, a halogenating agent, obtains 2,6-dihalo dimethyl- 17a, 21 19-nor-pregnen -4 Ri0-20ç one-3;

- dehalohydrate the latter by means of an alkali metal halide in dimethyl formamide;

- blocks the hydroxyl function in 3 of dimethyl-17a, 21 19-nor-pregnatétraen-1, 3,5 (10), 6 ol-3 Ri0-20ç of formula I

obtained, by means of a compound chosen from the group consisting of alkylating agents, dihydropyran, trityl chloride and trimethylsilyl chloride;

- obtains the product of general formula I in which R represents an alkyl group having from 1 to 4 carbon atoms or one of the tetrahydropyrannyl, trityl or trimethylsilyl radicals, and Ri represents an acyl residue having from 1 to 5 carbon atoms or the radical tetrahydropyrannyl, product of formula I from which the hydroxyl function is freed, where appropriate, in position 20 £, by the action of a base or of an acid, to obtain the product of general formula I in which R has the abovementioned meanings, and R 1 represents hydrogen, from which the 3-hydroxyl function is freed, where appropriate, by the action of an acid to obtain the product of general formula I in which R and R 1 represent hydrogen.

Under the preferred conditions of implementation, the method of the invention is carried out as follows:

- Methylation in position 21 is carried out by means of methyl iodide in the presence of a tertiary base such as potassium t-butoxide and one operates in toluene;

the reducing agent used to reduce the ketone function to 20 is an alkaline borohydride, such as that of sodium,

- The Birch reaction is carried out in the presence of ethanol;

the strong acid used during the isomerization of the double bond 5 (10) into 4 is hydrochloric acid and the operation is carried out in methanol;

the agent for the esterification of the hydroxyl function in 20C is a functional derivative of acetic acid, such as acetic anhydride, in pyridine, and the agent for the esterification of the hydroxyl function in 20C is the dihydropyran;

- The halogenating agent is bromine in acetic acid and one operates in ether;

- The alkali metal halide by means of which the dehalogenation is carried out is lithium chloride;

- The agent by means of which the hydroxyl function is blocked at 3 is dimethyl sulfate in the presence of sodium hydroxide, dihydropyran, trityl chloride or trimethylsilyl chloride;

- The base by means of which the hydroxyl function is released in position 20Ç is alcoholic potash or soda;

- The acid by means of which the hydroxyl function is released in position 20Ç is aqueous acetic acid;

- The acid by means of which the 3-hydroxyl function is released is aqueous acetic acid or a hydracid, such as hydrochloric acid.

In addition to the compounds of formula I, the following products are also new:

- ledimethyl-17a, 21 19-nor-pregnatrien-l, 3,5 (10) methoxy-3 one-20,

- dimethyl-17a, 21 19-nor-pregnatrien-1, 3,5 (10) methoxy-3 ol-20ç,

- dimethyl-17a, 21 19-nor-pregnen-5 (10) ol-20Ç one-3,

- dimethyl-17a, 21 19-nor-pregnen-4 ol-20 £ one-3,

- dimethyl-17a, 21 19-nor-pregnen-4acétoxy-20Ç one-3,

- ledibromo-2,6dimethyl-17a, 21 19-norpregnen-4acé-toxy-20ç one-3.

As already indicated, the products of general formula I are the starting products for the synthesis of steroid derivatives labeled with tritium.

Their application as such is also an object of the present invention, and is characterized in that a product of general formula I is reduced in which R and Ri have the

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meanings cited above, by the action of tritiated hydrogen in the presence of a catalyst, and subjects the (6,7-3H) dimethyl-17a, 21 19-nor-pregnatrien-1, 3,5 (10) RO- 3 Ri0-20ç obtained,

either when R represents the methyl radical and Ri represents an acyl radical having from 1 to 5 carbon atoms, the tetrahydropyrannyl radical, or hydrogen, directly to the action of lithium in ammonia in the presence of ethanol, according to Birch's reaction, to obtain, when Ri represents hydrogen or an acyl radical, the (6,7-3H) dimé-thyl-17a, 21 19-nor-pregnadien-2,5 (10) methoxy- 3 ol-20ç, or when Ri is the tetrahydropyrannyl radical, (6,7-3H) dimethyl * 17a, 21 19-nor-pregnadien-2,5 (10) 3-methoxy-tetrahy-dropyrannyloxy-20ç,

- either when R represents an aforementioned radical other than methyl or hydrogen, and Ri has the meanings other than hydrogen, to the action of an acid, such as acetic acid, or a hydracid, such hydrochloric acid, obtains (6,7-3H) dimethyl-17a, 21 19-nor-pregnatrien 1,3,5 (10) ol-3 Ri0-20ç, product which is treated with an agent methylation, such as dimethyl sulfate, subjects the (6,7-3H) dimé-thyl-17a, 21 19-nor-pregnatrien 1,3,5 (10) methoxy-3 Ri 0-20 £ obtained to the action lithium in ammonia according to the Birch reaction in the presence of ethanol, to obtain, when R 1 represents hydrogen or an acyl radical, also (6,7-3H) dimethyl-17a, 21 19-nor- pregnadien-2,5 (10) methoxy-3 ol-20ç, or when Ri is the tetrahydropyrannyl radical, (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-2,5 (10) methoxy- 3 tetrahydropyrannyloxy-20 ^.

General formula products:

GOLD

CH

RO

T

in which R and Ri are defined as above, and among these in particular (6,7-3H) dimethyl-17a, 21 19-nor-pre-gnatrien-1,3,5 (10) methoxy-3 ol-20 |, lead in particular to (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-2,5 (10) methoxy-3 ol-20 |, described in French patent No. 2,374,335 at name of the company ROUSSEL-UCLAF.

This product is an important intermediate during the synthesis of (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-4,9 dione-3,20.

According to the synthesis described in the patent of the titular company indicated above, one acts on (6,7-3H) dimé-thyl-17a, 21 19-nor-pregnadien-2,5 (10) méthoxy-3 ol-20 £, an aqueous weak acid such as acetic acid, obtains (6,7-3H) dimethyl-17a, 21 19-nor-pregnen 5 (10) ol-20 £ one-3, submits the latter with the action of pyridinium perbromide, acts on the (6,7-3H) dimethyl-17a, 21 19-nor-pregna-dien-4,9 ol-20ç one-3 resulting, an aqueous sulfochromic solution, for form the (6,7-3H) dimethyl-17a, 21 19-nor-pre-gnadien-4,9 dione-3,20 sought.

Le (6,7-3H) dimethyl-17a, 21 19-nor pregnadien-4,9-

dione-3.20 allows the easy assay of the specific progesterone receptor in the uterine cytosol or in the cytoplasm of tumor cells (breast cancer), and in tumors induced by DMBA (9,10-dimethyl-1, 2-benzanthracene) in rats.

This product has the advantage, compared to progesterone, of not binding to transcortin and of having an affinity for said progesterone receptor 6 to 8 times greater than the affinity of the latter.

The use of (6,7-3H) dimethyl-17a, 21 19-nor-pregna-dien-4,9 dione-3,20 for the characterization of the pro-gestogenic receptor has been described in numerous publications, such as by example: JP RAYNAUD and D. PHILIBERT, STEROIDS, July 1973, pp 89-97.

The starting material for the process for preparing the products of general formula I has been described in French patent 1,480,247.

The following examples illustrate, without limitation, the implementation of the invention.

Example 1

Ledimethyl-17a, 21 19-nor-pregnatetraen-1, 3,5 (10), 6 methoxy-3 ol-20 £.

Stage A: Dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 (10) methoxy-3 one-20.

126 g of potassium terbutylate are introduced into 1840 ml of toluene, the mixture is stirred for 15 minutes at room temperature under an inert atmosphere, then 306 g of 17a-methyl 19-nor-pregnatrien-1 are introduced in 15 minutes , 3.5 (10) one-20 in 900 ml of toluene, rinsed with 300 ml of toluene, leaves the reaction mixture for one hour with stirring at room temperature, then cools to around 0 ° C. 600 ml of methyl iodide are introduced and the reaction mixture is left stirring for 20 hours at a temperature in the region of 0 ° C. 6000 ml of water are then added, the aqueous phase is separated, and it is extracted several times with chloroform. The combined extracts are washed with water, then dried over sodium sulfate and evaporated to dryness under reduced pressure. 312 g of dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 (10) methoxy-3 one-20 are obtained. This product can be purified by chromatography on silica gel with elution with a cyclo-hexane-benzene-ethyl acetate mixture (5-3.5-1.5), mp 97 ° C.

The product was used as is for the next stage of the synthesis.

Stage B: Dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 (10) methoxy-3 ol-20 |.

60 g of the product obtained in the preceding stage and 17.5 g of sodium borohydride are introduced, with stirring at room temperature, into 300 ml of ethanol and 90 ml of water. The reaction mixture is brought to reflux with stirring for approximately 5 hours, then cooled to around 50 ° C., and poured under stirring into 900 ml of water. The crystallized product is drained, washed with water and dried.

59.6 g of dimethyl-17a, 2119-nor-pregna-trien-1,3,5 (10) methoxy-3 ol-20 £ are obtained, which are purified by chromatography on silica gel, eluting with the cyclo-hexane-ethyl acetate mixture (7-3), m.p. 70 ° C. The product is used as is for the next stage of the synthesis.

Stage C: Dimethyl-17a, 21 19-nor-pregnen-5 (10) ol-20ç one-3.

The solution of 85 g of product obtained in stage B, in 850 ml of tetrahydrofuran, is added over 40 minutes at -40 ° C., in 1400 ml of ammonia, added with stirring at -40 ° C., under an inert atmosphere, 42 ml of ethanol, then in approximately 40 minutes, 8.940 g of lithium, and leaves the reaction mixture with stirring for 15 minutes at approximately -40 ° C.

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This ethanol and lithium addition operation is repeated two more times. Then 127.5 ml of ethanol are added, the ammonia is distilled under an inert atmosphere until the internal temperature reaches 15 ° C. 850 ml of water are then added, the mixture is left to stir for approximately 1 hour, then approximately 20 hours at rest, under an inert atmosphere, at 20 ° C. It is drained, the precipitate rinsed with ether, the organic phases are collected, distilled under vacuum, the residue is taken up with 85 ml of tetrahydrofuran, added to the solution obtained 255 ml of acetic acid, and left to stir for 1 hour at 20 ° C under an inert atmosphere.

The solution is poured into a water-ice-ammonia mixture, the precipitate formed is drained, washed with water, taken up in 850 ml of ether, dried over sodium sulphate, then evaporated to dryness under vacuum.

The residue is pasted with stirring with 170 ml of petroleum ether (bp 64 ° -75 ° C), then drained and dried. 70.7 g of dimethyl-17a, 21 19-nor-pregnen-5 (10) ol-20 are obtained | one-3, mp 129 ° C.

This product is used as is for the next stage of the synthesis.

Stage D: Dimethyl-17a, 21 19-nor-pregnen-4 ol-20ç one-3.

7.85 g of product prepared in Stage C are introduced into 78.5 ml of methanol, 7.9 ml of 1N hydrochloric acid are added to the resulting solution and the reaction mixture is brought to reflux for approximately 1 hour.

The mixture is cooled, the precipitate is filtered off, washed with methanol and petroleum ether (bp 40 ° -70 ° C), dried under vacuum and 6.68 g of dimethyl-17a, 21 19-nor-pregnen- are obtained. 4 ol-20ç one-3.

The product can be purified by chromatography on silica gel, eluting with a methyl chloride-ethyl acetate mixture (9-1), mp = 221 ° C.

Stage E: Dimethyl-17a, 21 19-nor-pregnen-4 acetoxy-20ç one-3.

6.68 g of the product prepared in Stage D are introduced into 33.5 ml of pyridine and 16.5 ml of acetic anhydride, the reaction mixture is stirred for approximately 24 hours at 70 ° C., then poured into the mixture of 200 ml of 1N hydrochloric acid and ice, extracted several times with methylene chloride, washing the extracts with 1N hydrochloric acid with water and with a saturated aqueous solution of sodium bircabonate, dried over sodium sulfate sodium, treated with activated carbon + alumina, filtered and concentrated to dryness under vacuum.

The residue is taken up in isopropyl ether, filtered and dried under vacuum, and 6.3 g of dimethyl-17a, 21 19-nor-pre-gnen-4 acetoxy-20ç one-3 are obtained, which are purified by Chromatography on silica gel, eluting with a methylene chloride-ethyl acetate mixture (95-5) and recrystallization from a mixture of methylene chloride-isopropyl ether, M = 222 ° C.

Analysis: (C24H38O3)

Calculated: C 77.37; H 9.74;

Found: C 76.9; H 9.7

Stage F: 2,6-Dibromo-dimethyl-17a, 21 19-nor-pre-gnen-4 acetoxy-20ç one-3.

4.88 g of product prepared in Stage E is suspended in 50 ml of ether, then 27 ml of bromine, 15.6% solution in acetic acid, is introduced slowly at 15 ° C. The reaction mixture is stirred at about 15 ° C for 15 minutes. 100 ml of methylene chloride are then added, poured into water, washed with an aqueous solution of sodium bicarbonate, then with water, dried over sodium sulfate, filtered and a solution of 2,6-dibromo-dimethyl is obtained. -17a, 21 19-nor-pregnen-4 acetoxy-20ç one-3 which is used as is for the next stage of the synthesis without isolation of the desired product.

Stage G: Dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 ol-3 acetoxy-20ç.

4.88 g of lithium chloride are introduced into 50 ml of dimethyl formamide, heated using an oil bath at 120 ° C., then the solution of the dibromo product obtained is added in approximately 35 minutes, while distilling. stage F. Once the methylene chloride has been removed, the reaction mixture is maintained for approximately 15 minutes at 100 ° C., then allowed to cool to room temperature, added methylene chloride,

poured into water, washed with saturated aqueous sodium bicarbonate solution and water, extracted with methylene chloride, dried the combined organic phases over sodium sulfate, and concentrated in vacuo. The residue is taken up in methanol and purified by chromatography on silica gel, eluting with a methylene chloride-isopropyl ether mixture (95-5). 2.65 g of dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 ol-3 acetoxy-20c are thus obtained, mp = 246 ° C.

Stage H: Ledimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6-methoxy-3 acetoxy-20c.

1.92 g of product prepared in Stage F are introduced into 29 ml of methylene chloride and 19 ml of water, then 13 ml of 1N sodium hydroxide is added at 20 ° C. 1.45 ml of methyl sulphate and 190 mg tetrabutyl ammonium iodide.

The reaction mixture is stirred for 3 hours at 20 ° C., then poured into 100 ml of 0.1 N sodium hydroxide solution, extracted with methylene chloride several times, the organic phases are separated, washed with hydrochloric acid and at water, dry over sodium sulphate, concentrate, add isopropyl ether, concentrate, then cool, drain, wash with isopropyl ether, dry under vacuum and obtain 1.87 g of dimethyl-17a, 21 19- nor-pregnatetraen-1,3,5 (10,6-3-methoxy-acetoxy-20 |, mp = 162 ° C. The product can be purified by chromatography on silica gel, eluting with a cyclohexane-ethyl acetate mixture ( 85-15).

Stage I: Dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 methoxy-3 ol-20Ç.

1.87 g of product prepared in Stage H and 7.5 ml of 3N ethanolic potassium hydroxide are brought to reflux with stirring for 6 hours, then poured into 30 ml of water, extracted several times with methylene, wash the combined extracts with hydrochloric acid and then with water, dry over sodium sulfate, treat with alumina, concentrate to dryness under vacuum, take up the residue with isopropyl ether, cool, spin dry the product crystallized, washed with isopropyl ether and dried under vacuum. 1.13 g of dimethyl-17a, 21 19-nor-pre-gnatetraen-1,3,5 (10), 6 methoxy-3 ol-20 £ are obtained, which can be purified by gel chromatography. silica, eluting with a cyclohexane-ethyl acetate mixture (90-10).

The product purified to a melting point of 141 ° C.

Example 2

Stage A: (6,7-3H) dimethyl-17a, 21 19-nor-pregna-trien-1,3,5 (10) methoxy-3 ol-20 £.

The reaction mixture consisting of 65 mg of dimethyl-17a, 21 19-nor-pregnaté-traen-1,3,5 (10), 6 methoxy-3 ol-20ç, 20 mg of palladium black is cooled with liquid nitrogen. and 2.5 ml of ethyl acetate, then introduced under vacuum, 7.95 ml of tritium with an activity of 20 Ci then the reaction mixture is allowed to return to room temperature, stirred for 3

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hours, cool again with liquid nitrogen and recover the excess tritium, then allow the reaction mixture to return to room temperature, filter the catalyst, wash it with ethyl acetate, evaporate the filtrate under vacuum and obtain 65 mg of the crude product in the form of a resin.

The crude product is purified by thin layer chromatography on silica gel, eluting with a methylene chloride-acetone mixture (1-1). The eluate is then filtered, evaporated to dryness, the residue is taken up in the benzene-ethyl acetate mixture (10-1) and after evaporation of the solvent, 55 mg of product is obtained, Rf = 0.38, of which the specific activity is 56.5 Ci / m mol.

Stage B: (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-2,5 (10) methoxy-3 ol-20ç.

25 ml of liquid ammonia (cooled to -35 ° C and -40 ° C) are added to 25 ml of 55.7 mg (6.7-3H) dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 ( 10) 3-methoxy ol-20Ç, in solution in

5 ml of tetrahydrofuran and 0.5 ml of ethanol, then introduced in small portions 200 mg of lithium. The reaction mixture is stirred for 1 hour at approximately -35 ° C, then 10 ml of ethanol is added slowly. The ammonia is then removed by bringing the reaction mixture to room temperature, adding 50 ml of water and extracted several times with benzene, drying the organic phase over sodium sulfate, evaporating to dryness under vacuum and obtaining 55 mg of (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-2,5 (10) methoxy-3 ol-20ç in the form of a resin which is used as it is for the following stage of the synthesis of (6,7-3H) dimethyl-17a, 21 19-nor-pregna-dien-4,9 (10) dione-3,20.

The product obtained can be purified by chromatography on silica, eluting with a benzene-ethyl acetate mixture is (10-1). Rf: 0.38.

This product is identical to that described in Swiss patent application No. 15 389/77 (No. 1769) filed on December 14, 1977 by the titular Company.

B

Claims (3)

629826 2. Compounds of formula I according to claim 1, the names of which follow: - ledimethyl-17a, 21 19-nor-pregnatétraen-1, 3,5 (10), 6 diol-3,20Ç, - Iedimethyl-17a, 21 19-nor-pregnatétraen-1, 3,5 (10), 6 methoxy-3 ol-20ç, - ledimethyl-17a, 21 19-nor-pregnatétraen-1, 3,5 (10), 6 methoxy-3 acetoxy-20ç and - dimethyl-17a, 21 19-nor-pregnatetraen-1,3,5 (10), 6 ol-3 acetoxy-20ç. 3. Process for the preparation of the compounds of formula I above in which R represents an alkyl group having from 1 to 4 carbon atoms or one of the tetrahydropyrannyl, trityl or trimethylsilyl radicals and Ri represents an acyl residue having from 1 to 5 atoms carbon or the tetrahydropyrannyl radical, characterized in that: - subject to methylation at position 21, by means of a methyl halide, methyl-17a 19-nor-pregna-trien-1,3,5 (10) 3-methoxy-one-20, - faitagirsurlediméthyl-17a, 21 19-nor-pregnatrien-l, 3,5 (10) methoxy-3 one-20 resulting, a reducing agent to obtain dimethyl-17a, 21 19-nor-pregnatrien-l, 3,5 (10) 3-methoxy ol-20§, - subjects the latter to the action of lithium in ammonia, - isomerizes dimethyl-17a, 21 19-nor-pregnen-5 (10) ol-20 | one-3 obtained, by means of a strong acid, in dimé-thyl-17a, 21 19-nor-pregnen-4 ol-20 | one-3, - subject the latter to the action of an esterification or etherification agent, - acts on dimethyl-17a, 21 19-nor-pregnen-4 Ri0-20ç one-3 resulting, Ri having the above-mentioned meanings, a halogenating agent, obtains 2,6-dihalo-dimé-thyl-17a, 21 19-nor-pregnen-4 Rt0-20ç one-3, - dehalohydrate the latter by means of an alkali metal halide in dimethyl formamide and - blocks the hydroxyl function in 3 of dimethyl-17a, 21 19-nor-pregnatétraen-1,3,5 (10,6 ol-3 Ri0-20-ç obtained by means of a compound chosen from the group consisting of alkylating agents, dihydropyran, trityl chloride and trimethylsilyl chloride. 4. Method according to claim 3, characterized in that one operates under the following conditions: - Methylation in position 21 is carried out by means of methyl iodide in the presence of a tertiary base such as potassium t-butoxide and one operates in toluene; - The halogenating agent is bromine in acetic acid, and one operates in ether; - The alkali metal halide by means of which the dehalogenation is carried out is lithium chloride. 5. Process for the preparation of the compounds of formulas I above in which R represents an alkyl group having from 1 to 4 carbon atoms or a tetrahydropyrannyl, trityl or trimethylsilyl radical and Ri represents hydrogen, characterized in that l compounds of formula I are prepared by the process according to claim 3, in which R has the meaning indicated above and R1 represents an acyl residue having from 1 to 5 carbon atoms or the tetrahydropyrannyl radical, and the hydroxyl function in position 20 £ by action of a base or an acid. 6. Process for the preparation of the compounds of formula I above in which R and Ri represent hydrogen, 20 characterized in that compounds of formula I are prepared by the process according to claim 3, in which R represents an alkyl group having from 1 to 4 carbon atoms or one of the tetrahydropyrannyl, trityl or trimethylsilyl radicals and Ri represents a acyl residue having 1 to 5 carbon atoms or the tetrahydropyrannyl radical, the hydroxyl function is released in position 20 £ by the action of a base or an acid to obtain compounds of formula I in which R represents an alkyl group having from 1 to 4 carbon atoms or a tetrahydropyrannyl, trityl or trimethylsilyl radical and R 1 represents hydrogen, and the hydroxyl function is released in position 3 by the action of an acid. 7. Use of the compounds according to claim 1 or 2, for the synthesis of corresponding compounds labeled with tri-tium, characterized in that said compounds are reduced 35 formula I, in which R and Ri have the meanings given in claim 1, by the action of tritiated hydrogen in the presence of a catalyst and subjects the (6,7-3H) dimethyl-17a, 21 19-nor pregnatrien- 1, 3.5 (10) RO-3 Ri0-20Ç obtained, when R represents the methyl radical and Ri represents an acyl radical 40 having from 1 to 5 carbon atoms, the tetrahydropyrannyl radical or hydrogen, to the action of lithium in ammonia in the presence of ethanol, to obtain, when R 1 represents hydrogen or an acyl radical, (6,7-3H) dimé-thyl-17a, 21 19-nor pregnadien-2, 5 (10) 3-methoxy ol-20ç or, 45 when R 1 is the tetrahydropyrannyl radical, (6,7-3H) dimé-thyl-17a, 21 19-nor pregnadien-2,5 (10 3-methoxy tetrahydro- pyrannyloxy-20 ^. 8. Use of the compounds according to claim 1 or 2, for the synthesis of corresponding compounds labeled with tri- 50 tium, characterized in that said compounds of formula I are reduced, in which R and Ri have the meanings given in claim 1, by the action of tritiated hydrogen in the presence of a catalyst and subjects the (6,7 -3H) dimethyl-17a, 21 19-nor pregnatrien-1,3,5 (10) RO-3 Ri0-20- | obtained, when 55 R represents an aforementioned radical other than methyl or hydrogen and Ri has the meanings other than hydrogen, to the action of an organic acid or of a hydracid, obtains the (6-7 -3H) dimethyl-17a, 21 19-nor-pregnatrien-1,3,5 (10) ol-3 Ri0-20Ç, product which is treated with a methylating agent, 60 submit (6,7-3H) dimethyl-17a, 21 19-nor-pregna-trien-l, 3,5 (10) 3-methoxy Ri0-20 | obtained by the action of lithium in ammonia in the presence of ethanol, to obtain, when R 1 represents hydrogen or an acyl radical, also (6,7-3H) dimethyl-17a, 21 19-nor pregna -65 dien-2,5 (10) 3-methoxy ol-20ç or, when Ri is the tetrahydropyrannyl radical, (6,7-3H) dimethyl-17a, 21 19-nor-pregnadien-2,5 (10) 3-methoxy-tetrahydropyrannyloxy-20ç. 2 CLAIMS 1. Steroids of general formula: in which R represents hydrogen, an alkyl group having from 1 to 4 carbon atoms or a tetra-hydropyrannyl, trityl or trimethylsilyl radical, and Ri represents hydrogen, an acyl radical having from 1 to 5 carbon atoms or the tetrahydropyrannyl radical. 3 629826