DE1958533B2 - PROCESS FOR THE PRODUCTION OF STEROIDS CONTAINING 17 ALPHA-PROPADIENYL GROUPS - Google Patents

Description

I H

Zl

R ₁₁

RcO H R _n

Z7

where Rs is hydrogen, alkyl with! up to 3 carbon atoms, Cycloalkyl of 5 to 7 carbon atoms or alkanoyl of 2 to 4 carbon atoms means Re is hydrogen, 6 <x -methyl or 7'-methyl, R7 is hydrogen or methyl and Re is hydrogen, fluorine, chlorine or methyl, with the proviso that if the rings A and B are represented by the formula image Zl, where Re> represents hydrogen, as well as R2 and Rs, which can be identical or different, Signify hydrogen or alkanoyl with 2 to 4 carbon atoms, R «then represents hydrogen, characterized in that one compounds of the general formula

R _S O

/ V

R ₅ O

Z2

Z 3

40

45

60

L (

C = C-CH, -NR ₁ V, Y

R ₄ \

ίο

where Ri, R4 and Z have the above meaning, wöbe the hydroxyl or keto groups in Z may be protected by methylation 'Rio' and Rio "can be the same or different and each represent alkyl of 1 to 3 carbon atoms or together with the nitrogen atom form a pyrrolidino or piperidino ring Rk represents alkyl having 1 to 3 carbon atoms unc Y- stands for a nucleofugic leaving group, mi a complex metal hydride in an inert one Reacts solvent, optionally protected «Z-structures of the reaction products obtained ir unprotected Z-structures converted and obtained «compounds of the formula 1, in which R2 is water substance, if necessary then by reaction with an acylating agent with 2 bi: 4 carbon atoms in compounds of the formula I in which R2 is an alkanoyl group with 2 bii 4 carbon atoms, or by reaction with a methylating agent in compounds dei Formula I, in which R2 is methyl, converted.

OR ₁ ,

Z 6

In US Pat. Nos. 33 92 165 and 33 92 16f, steroid compounds that have a <in the 17-position Hydroxyl group and optionally one with one

Have methyl radical substituted propadienyl group, has been disclosed by formula. However, it has been shown that it is after that in these patents specified procedure is not possible to make the connections in question. It has now been recognized that the production of the formulas specified there and similarly structured steroid compounds with a Propadienyl group in the 17-position according to the formula I. is possible in the mode of operation specified in the claim without difficulty

The ring structures A and B of the steroid compounds of the formula which are represented by the formulas Zl to Z7 are shown, have hydroxyl or keto groups, which are attacked by the reaction conditions can be, among which either the starting materials used in the last stage manufactures, or works at the last stage yourself. It is therefore a preferred feature of the invention to have this Structures by customary protecting groups, which are stable under the respective reaction conditions protection. Correspondingly protected groups can easily be converted into the desired ones in a known manner Introduce structures. In the reactions according to the invention, the Zl to Z7 structures can therefore in those cases in which appropriately protected forms are possible, in unprotected forms or preferably protected form.

In the process according to the invention, the complex metal hydride can be, for example, lithium aluminum hydride. The reaction can be carried out at temperatures between about -80 ° and + 8O ⁰ C, wherein the inert solvent may, for example, use of diethyl ether or tetrahydrofuran. Neither temperature nor solvent are critical. The nucleofuge group Y "can be, for example, a chlorine, bromine, iodine, methanesulphonate or p-toluenesulphonate ion. The substituents P10, Rio 'and Rio" are preferably each the same and preferably each represent methyl.

The acylation process which may be necessary can be used in the acylation of steroid alcohols known manner. A method is preferred in which only those in position 17 located OH group is acylated.

In the case of the compounds which have a large number of OH groups, one OH group is in position 3 secondary or phenolic, one OH group in position 16a secondary and one OH group in position 17JJ tertiary. It is well known that acylation reacts first the secondary as phenolic and finally the tertiary hydroxyl groups, while one Saponification first on the phenolic, then on the secondary and finally on the tertiary hydroxyl groups accordingly, depending on the hydroxyl groups to be acylated, the strength and degree of Acylation can be selected. For the acylation in position 3 and / or 16a, acids or acid halides can be used or acid anhydrides of the formulas ACOOH, ACO-Hal and (ACO) 2O, wherein A is alkyl with 1 to 3 means carbon atoms and Hai stands for bromine or chlorine, as well as use their mixtures. If If an acetyl group is desired, acylation is preferably carried out with acetic anhydride. The acylation can be carried out in the presence of an inert solvent or in an excess of acylating agent will. Preferably it is applied in the presence of an acid binder, e.g. B. pyridine, made, wherein at temperatures between -10 ° and 50 ° C

works To acylate all three positions one can work under more severe conditions, i.e. in the presence a strongly acidic catalyst such as p-toluenesulfonic acid or perchloric acid. When using such catalysts you can in addition to the above named acylating agents or enol acylates, preferably esters of "isopropenyl alcohol", d. H. Isopropenyl acetate, use a All other measures are familiar to the person skilled in the art. How to get the desired Combination of free OH groups and acylated positions can therefore be achieved does not need any further details to be discussed.

For the methylation process stage, the methylating agent used is, for example, a methyl halide, preferably methyl iodide. This is preferably used in an excess, for example between about 1 and £ 0 equivalent of halide per equivalent of the anion of the steroid compounds strong base, for example sodium or potassium amide, in liquid. Ammonia or with methyllithium in diethyl ether The reaction treated with a strong base can be carried out at temperatures between about -30 ° and + 30 ⁰ C, using from 1 to 1.2 equivalent of strong base per equivalent of compounds of formula I.

The starting compounds of the formula V can be prepared as follows:

Compounds of the formula II in which Ri, R4 and Z are above Have meaning, the hydroxyl and carbonyl groups in the formulas Zl to Z7 are optionally protected, for example by methyl, tetrahydropyranyl or ethylenedioxy groups, are made with connections of the form! ! V, where X

for lithium, sodium, potassium, -MgBr, -MgJ,, or

stands, and Rio 'and Rio "have the above meaning,

in an inert organic solvent, such as. B. tetrahydrofuran, if X is -MgBr, -MgJ or lithium, or liquid ammonia, diethyl ether, liquid ammonia / tetrahydrofuran, dioxane, pyridine or dioxane / pyridine, if X is sodium or potassium, reacted and the reaction product then, for example, with Hydrolyzed with the aid of an aqueous ammonium chloride solution The compounds of the formula IHa thus obtained, in which Ri, R4, Rio ', Rio "and Z have the above meaning, are then treated with compounds of the formula VI, in which Rio has the above meaning, in an inert solvent, e.g. acetone at temperatures from -20 ° to +30 ⁰ C, converted to compounds of the formula V.

Processes for protecting carbonyl and hydroxyl groups are known from the literature. See, for example "The Protection of Carbonyl and Hydroxyl Groups" by John F. W. K e a n a in "Steroid Reactions, An Outline for Organic Chemists «, Carl D j e r a s s i, Holden-Day Inc., San Francisco (1963), chapter 1.

The protective group is preferably split off by treatment with acids in one of the Reaction conditions inert organic solvent, for example with the aid of 11 η-hydrochloric acid in Methanol or glacial acetic acid and water at room temperature.

The compounds of general formula I are valuable pharmaceuticals. They are particularly suitable

others as fertility inhibitors. The compounds of the general formula I ₁ in which Z stands for the structures Z1 to Z3 have an estrogenic effect. The compounds of the general formula I in which Z stands for the structures Z4 to Z8 have a progestational effect.

The dose to be administered daily is between about 0.01 and 10 mg. Suitable doses for internal Administration range between about 0.005 and 10 mg, in admixture with a solid or liquid carrier or Diluents. ι ο

A preferred compound is 17 "-Propadienylöstra-4-en-3 / M 7/3 dioL

A pharmaceutical preparation - e.g. B. a capsule - with the compounds of the invention as an active ingredient can be formulated as follows: '5

23 parts by weight of 17 "-Propadienylöstra-4-en-3p, 17jJ-diol, 2 parts by weight tragacanth, 87 parts by weight lactose, 5 parts by weight corn starch, 3 parts by weight talc, O ^ parts by weight of magnesium stearaL

The ^ ° given in the following examples NMR spectra were measured at 60 megahertz in CDCb solution, and using tetramethylsilane as standard.

Example 1 -5

17Ä-Propadienyl-3-methoxyestra-13,5 (10) -trien-170-ol

A. Manufacture of the raw material

a) 17oc- (3-dimethylamino-1-propynyl) -3-methoxyestra-1,3,5 (10) -trien-170-ol

A mixture of 15.8 g of 17'-ethynyl-3-methoxyestra-13.5 (10) -trien-17 /? - ol, 15.0 ml of dimethylaminomethanol, 500 mg of copper (I) chloride, 8.5 ml Glacial acetic acid and 125 ml of dioxane are ^{kept at 70 °} C. for 5 hours. Ice water is then added, the pH is adjusted to 10 and the title compound is extracted with ether. It stays a

Foam back with [«]" '8.84 (c = 1, CHCb).

Yield: 70% of theory.

b) 17 <x- (3-Dimethylamino-1-propynyl) -3-methoxyestra-13,5 (10) -trien-17j3-ol-methiodide

A mixture of 10.0 g of the above process product, 290 ml of acetone and 87 ml of methyl iodide is

Maintained at 0 ^° C. for 24 hours. The desired product precipitates in crystalline form and is isolated by filtration, melting point: 237 to 239 ° C .; Yield: 95% of theory

B. Method according to the invention.

c) Woc-Propadienyl-S-methoxyöstra-

13.5 (10) -trien-170-ol

A suspension of 3.006 g of the process product obtained above in 65 ml of anhydrous tetrahydrofuran is mixed at -75 ° C. with 11.25 ml of a 0.525 molar lithium aluminum hydride-tetrahydrofuran solution. ^{After stirring for 2} hours at -10 ° C., a clear solution is obtained which is kept at room temperature overnight. It is cooled to 0 ° C., saturated aqueous ammonium chloride solution is added and the title compound is extracted with ether. To 129.5 hereby obtained a quantitative yield, calculated over all the above process steps, the crystalline material of mp to 130.5 ⁰ C. [φ = + 7.18 ° (c = 1, CHCb). Yield: 90% of the

Example 2

Among those described in Example 1

Terms and use of the following

Starting material:

17 "-äthinylöstra-4-en-3A17 ^ -diol leads to 17 _Ä -propadienylöstra-4-en-3A17 /? - d.ol, mp 72 to 79 ° C (yields of the individual stages: 85% of theory, 70% and 65% of theory)

Example 3

17Ä-PropadienyI-3-methoxyestra-2,5 (10) -diene-17jS oil

A. Manufacture of the raw material.

a) 17flt- (3-Dimethylamino-l-propynyl) -3-methoxyestra-2,5 (l 0) -dien-170-ol

A Grignard mixture prepared from 1.50 g of magnesium, 4.68 g of ethyl bromide and 70 ml of tetrahydrofuran is added dropwise with 5.3 g of dimethylaminopropine dissolved in 10 ml of tetrahydrofuran. After the evolution of ethane has ceased, a solution of 1.716 g of 3-methoxyestr? -2,5 (10) -dien-17-one in 30 ml of tetrahydrofuran is added dropwise, the temperature being kept at 0 to 5 ° C. during the addition is, and then allowed to react at 20 to 25 ° C for 4 hours. After adding 100 ml of 2N sodium hydroxide solution, the mixture is ^{concentrated in vacuo at temperatures not exceeding 30 °} C. to a total volume of 100 ml. The concentrate is extracted with ether (5 25 ml), whereby to facilitate phase separation centrifuged. The title compound is obtained by evaporating the dried ether solutions and suctioning off any excess dimethylaminopropine. Yield: 60% of theory.

b) 17a- (3-Dimethylamino-1-propynyl) -3-methoxyestra-2,5 ( 10) -diene-170-ol-methiodide

2.0 g of the process product obtained above are dissolved in 30 ml of acetone. After addition of 3.5 g of methyl iodide, the mixture is kept 18 hours 8 ⁰ C. The title compound crystallizes out, is filtered off and washed with anhydrous ether. Yield: 95% of theory.

B. Method according to the invention.

c) 17a-Propadienyl-3-methoxyestra-2,5 (10) -dien-17 /? - ol

9.3 ml of a 0.525 molar lithium aluminum hydride-tetrahydrofuran solution are added at -75 ° C. to a suspension of 2.5 g of the process product obtained above in 50 ml of tetrahydrofuran. The mixture is brought to -10 ⁰ C and up to obtain a clear solution (about 90 minutes) stirred and then held for 12 hours at room temperature. 100 ml of aqueous 2N sodium hydroxide solution, which contains 50 ml of di-tert-butylcresol, are added, whereupon the mixture is concentrated in vacuo to a total volume of 100 ml. After extraction with 5 × 20 ml of ether, phase separation using a centrifuge, drying of the ether solutions over potassium carbonate and evaporation, 17-x-propadienyl-3-methoxyestra-2,5 (10) -dien-170-ol is obtained. Mp. 160 to 163 ° C from methanol. Yield: 50% of theory.

Example 4
17a-Propadienylöstra-5 (10) -en-17j9-ol-3-one

2.0 g of 17'-propadienyl-3-mezhoxyöstra-2,5 (10) -dien-17 / J-ol, obtained according to Example 3, are dissolved in a mixture of 20 ml of glacial acetic acid and 2 ml of water. After 2 hours, 200 ml of water are added and the product is extracted with ethyl acetate (5x10 ml). To Evaporation of the ethyl acetate extracts leads to 17 <x-Propadienylöstra-5 (lo) -en-17 | 9-ol-3-one as crystalline Solid with a melting point of 116 to 122 ° C. Yield: 75% of theory.

Example 5
Wa-Propadienylöstra ^ -en-nfl-ol-S-one

5.5 g of 17'-propadienyl-3-methoxyestra-2,5 (10) -dien-17S-ol, obtained according to Example 3, are dissolved in a mixture of 50 ml of methanol and 1.5 ml of HN aqueous hydrochloric acid and 30 Maintained at 30 ^° C. for minutes. After dilution with 100 ml of water, the product is extracted with methylene chloride (5 × 15 ml). After evaporation of the dried methylene chloride solutions and subsequent recrystallization of the residue from cyclohexane, pure 17'-propadienylöstra-4-en-17j3-ol-3-one with a melting point of 135 ° to 137.5 ° C. is obtained. Yield: 80% of theory.

Example 6

Following the procedure of Examples 3 and 5 using the following starting points:

a) estrone-3-tetrahydropyranyl ether,

b) 3-methoxy-13-ethylgona-2,5 (10) -dien-17-one,

following connections:

a) 17a-Propadienylöstra-1,3,5 (10) -triene-3, l 7j3-dioi [from methylene chloride / hexane (1: 5) \ mp. 134 to 136 ° C,

b) 13-ethyl-17 "-propadienylgona-4-en-170-ol-3-one, M.p. 122 to 125 ° C,

(Yields of the individual stages: 60% of theory and 60% of theory)

Example 7

1 78- acetoxy-3-methoxy-17 "-propadienylestra- U, 5 (10) -triene

60

65

A solution of 297.8 mg p

xyöstra-U ^ (10) -trien-17ß-ol (example) and 2 mg of p-toluenesulfonic acid in 6 ml of isopropenyl acetate are kept at room temperature for 18 hours. Ether is added, the solution is evaporated to dryness after washing with ice-cold sodium bicarbonate solution and drying over magnesium sulfate, and after recrystallization from methanol the 17.fi-acetoxy-3-methoxy-17'-propadienylöstra-U3 (10) -triene is obtained from m.p. 89 to 90 ⁰ C [<x] d = + 9.27 ° (C = 1, CHQa). Yield: 75% of theory.

Example 8

17j3-Methoxy-17 * -propadienylestra-4-en-3-one
A. Manufacture of the raw material

a) 17a- (3-Dimethylamino-1-propynyl) -3-methoxyestra-2,5 (10) -dien-17j3-ol

A Grignard mixture prepared from 1.50 g of magnesium, 4.68 g of ethyl bromide and 70 ml of tetrahydrofuran is added dropwise with 5.3 g of dimethylaminopropine dissolved in 10 ml of tetrahydrofuran. After the evolution of ethane has ceased, a solution of 1.716 g of 3-methoxyestra-2,5 (10) -dien-17-one in 30 ml of tetrahydrofuran is added dropwise, the temperature being kept at 0 to 5 ° C. during the addition , and then allowed to react at 20 to 25 ° C. for 4 hours. After adding 100 ml of 2 N sodium hydroxide solution, the mixture ^{is concentrated in vacuo at temperatures not exceeding 30 °} C. to a total volume of 100 ml. The concentrate is extracted with ether (5 × 25 ml), centrifuging to facilitate phase separation. The title compound is obtained by evaporating the dried ether solutions and suctioning off any excess dimethylaminopropine.

b) 17 «- (j-Dimethylamino-1-propynyl) -3-methoxyestra-2,5 ( 10) -dien-17β-ol-methiodide

2.0 g of the process product obtained above are dissolved in 30 ml of acetone. After adding 3.5 g Methyl iodide is kept at 8 ° C. for 18 hours. The title compound crystallizes out, is filtered off and washed with anhydrous ether.

B. Method according to the invention.

c) 17 "-Propadienyl-3-methoxyestra-2,5 (10) -dien-17j? -ol

9.3 ml of a 0.525 molar lithium aluminum hydride / tetrahydrofuran solution are added at -75 ° C. to a suspension of 2.5 g of the process product obtained above in 50 ml of tetrahydrofuran. The mixture is cooled to - 10 ⁰ C and brought up to obtain a clear solution (about 90 min.) Was stirred, and then kept for 12 hours at room temperature. 100 ml of aqueous 2N sodium hydroxide solution containing 50 ml of di-tert-butylcresol are added, whereupon the mixture is concentrated in vacuo to a total volume of 100 ml. After extraction with 5 × 20 ml of ether, phase separation using a centrifuge, drying the ether solution over potassium carbonate and evaporation gives 17α-propadienyl-3-methoxyestra-2 £ (10) -dien-17β-ol.

d) 3,17β-Dimethoxy 17oc-propadienylöstra-23 (10) -diene

A solution of 3.24 g of 17'-propadienyl-3-methoxyestra-25 (10) -dien-17β-ol in 50 ml of diethyl ether are added. The mixture is kept at reflux temperature for two hours and then 2J5 g of methyl iodide are added, whereupon the ammonia is allowed to evaporate. Dimethoxy

609 526/457

IS 58

ίο

17 "-propadienylöstra-2,5 (10) -diene. Yield: 30% of the Theory.

e) 17j3-Methoxy-17 "-propadienylestra-4-en-3-one

5.5 g of 3,17j9-dimethoxy-17 "-propadienylöstra-2,5 (10) -diene are dissolved in a mixture of 50 ml of methanol and 1.5 ml of 11 N aqueous hydrochloric acid and 30 minutes kept at 30 ° C. After dilution with 100 ml of water, the product is extracted with methylene chloride (5 15 ml). After evaporation of the dried methylene chloride solution and subsequent recrystallization the residue from cyclohexane gives pure 17/3-methoxy-17 «-propadienylöstra-4-en-3-one from Melting point 115.5 ° C. Yield: 80% of theory.

Example 9
3.beta., 1 7 β- diacetoxy-17a-propadienylöstra-4-ene

According to Example 7, using; o 17a-propadienylöstra-4-en-3 / ?, 17j9-diol, those in the title are obtained called connection. NMR spectrum:

I3-CH3 = 00.94 ppm

170-OCOCHa = (51.97 ppm ^

3-OCOCH3 = (52.04 ppm

Yield: 40% of theory.

10

Example 10

3ß- acetoxy-17a-propadienylestra-4-en-17j3-ol

0.8 g of 17a-Propadienylöstra-4-en-3 / J, 17j9-diol (Example 2) are added to a solution of 4.4 ml of acetic anhydride in 13.0 ml of pyridine, the resulting mixture is 17 hours at room temperature (20 ° C) stirred, then poured into 100 ml of water and 5ma.l with 10 m! Methylene chloride The combined methylene chloride extracts are dried over anhydrous sodium sulfate, the solvent is evaporated in vacuo, and after recrystallization of the residue from 95% ethanol, the title compound of mp. 107 to 108.5 ⁰ C obtained. Yield 80% of theory.

Example 11

3-methoxy-17 "-propadienylöstra-2,5 (10) -dien -170-ol

A. Manufacture of the raw material

a) 17a- (3-N-piperidino-1-propynyl) -aZ ^ l 0) -diene- 1

200 mg of copper (I) -ch] oride are added to a solution of 50 g of 17'-ethynyl-3-methoxyestra-2 ^ 5 (10) -dien-17 /? - ol in 50 ml of dioxane. 5 g of N-piperidino-carbinol and 02 ml of glacial acetic acid are added. The mixture is kept at a temperature between 40 and 50 ° C. for 1 hour, then cooled and the pH is adjusted to 9 by adding a 2 N aqueous sodium hydroxide solution is then diluted with water and the precipitated oil is extracted with methylene chloride. The methylene chloride extract is washed 3 times with water, then dried over anhydrous sodium sulfate, filtered off and evaporated to dryness. Here you get that

17 <x- (3'-N -piperidino-1-propynyl) -3-methoxyestra-2,5 (10) -dien-170-ol.

b) 17oc- (3-N-piperidino-1-propynyl) -3-methoxyestra-2,5 (10) -dien-17j3-ol-methiodide

50 g of 17 "- (3-N-piperidino-1-propynyl) -3-methc: <yöstra-2,5 (10) -dien-17 | 3-ol are dissolved in 50 ml of acetone and the solution with stirring with 5 ml of methyl iodide offset. The mixture is then stirred for a further 30 minutes at room temperature. The mixture is with 150 ml of diethyl ether diluted, whereby a precipitate is formed, which is filtered off and washed with diethyl ether will. After drying, the 17a- (3-N-piperidi-

no-1-propynyl) -3-methoxyestra-2,5 (10) -dien-17j9-ol methiodide.

B. Method according to the invention.

c) 17 <x-PropadienyI-3-methoxyestra-

2,5 (10) -dien-17j9-ol

14 g of 17 "- (3-N-piperidino-1-propynyl) -3-methoxyestra-2,5 (10) -diene-17 | 9-ol-methiodide are suspended in 420 ml of tetrahydrofuran and the suspension with vigorous stirring with 4.5 ml of a 70% solution of Sodium bis (2-methoxyethoxy) aluminum hydride is added in benzene, the addition in 3 portions he follows. The suspension obtained is stirred at room temperature for 4 hours. The excess of the Hydrids is then added by adding 1 ml of water and then 5 ml of a 10% aqueous Sodium hydroxide solution decomposes. The precipitate formed is filtered off and washed with tetrahydrofuran washed. The filtrate and wash solution are combined and in vacuo to one evaporated syrupy residue. The residue is dissolved in methylene chloride and the obtained The solution was washed several times with water until the washing solution had a neutral reaction. After that the solution dried over sodium sulfate, filtered off and evaporated to dryness. This leads to the

17 "-Propadienyl-3-methoxyestra-2,5 (10) -dien-17j3-ol from m.p. 160 to 163 ° C (from methanol) (protected Form of the compounds described in Examples 4 and 5).

Example 12

17α-Propadienyl-3-methoxyöstΓa-2.5 (10) -dien-17β-ol

A. Manufacture of the raw material.

a) 17 "- (3-N-pyrrolidino-1-propynyl) -3-methoxyestra-2,5 (1O) -dien-170-ol

Using the procedure described in section a) of Example 11, but at Replacement of the N-piperidino-carbinol used there by equivalent proportions of N-pyrrolidino-carbinol one arrives at 17 "- (3-N-pyrrolidino-1-propynyl) -3-methoxyestra-2 ^ (10) -dien-170-ol.

b) 17 "- (3-N-pyrrolidino-1-propynyl) -i-methoxyostra-24 (10) -dien-170-ol-methiodide

Using the method described in section b) of Example 11, but replacing the 17 "- (3-N-Pi _pe ridino-1-propinyO-3-methoxyostra-23 (10) -dien-170-ol used there equivalent proportions of! 7a- {3-N-pyrrolidino-l-propynyl) -3-methoxyestra-

11 12

2,5 (10) -dien-17 /? - ol leads to the 17 "- (3-N-pyrroli replacement of the 17" - (3-N-piperidino-l

dino-l-propynyl) -3-methoxyöstra-2,5 (10) -diene-17j? -ol-propynyl) -3-methoxyöstra-2,5 (10) -dien-17j9-ol-methjo-

methiodide. did by equivalent proportions of 17 "- (3-N-Pyrrolidi

B. Method according to the invention. no-1-propynyl) -3-methoxyöstra-2,5 (10) -diene-17 /} - ol-

. , _,. ._, .. ,, ...,,. , -, «ι ^s methiodide leads to 17 & -propadienyl-3-metho

c) 17 "-Propad ₁ enyl-3-methoxyostra-2,5 (10) -d.en-17 ^ ol _xyöst ra-2,5 (10) -dien-17β-ol with a melting point of 160 to 163 ° C

Using the in section c) of the (from methanol) (protected form of that in the examples <

Example 11 described method, but with and 5 described compounds).

Claims (1)

Claim: Process for the preparation of steroids of the formula 1 containing 17a-propadienyl groups where Ri denotes alkyl with 1 to 3 carbon atoms, R2 denotes hydrogen, methyl or aikanoyl with 2 to 4 carbon atoms, R4 denotes hydrogen, hydroxy or alkanoyloxy with 2 to 4 carbon atoms and Z denotes the rings A and B as well as substituents on them and through the formula images Zl to Z8 is reproduced.