US2933510A - 3-keto-4-halo-delta 4, 5 steroid - Google Patents
3-keto-4-halo-delta 4, 5 steroid Download PDFInfo
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- US2933510A US2933510A US554419A US55441955A US2933510A US 2933510 A US2933510 A US 2933510A US 554419 A US554419 A US 554419A US 55441955 A US55441955 A US 55441955A US 2933510 A US2933510 A US 2933510A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to new steroid compounds and the method of preparing them. More particularly, it relates to certain physiologically active 3-lreto-4-halo-A' compounds and the method of preparing them.
- the invention provides 4-halo derivatives of active androgenic, anabolic, progestational and corticoid hormones.
- the components of this invention have hormone activity and, more specifically, variously have advantageous anabolic, androgenic, progestational and cortical activity with minimal side efiects. It is well known that the active steroid hormones normally exhibit a plurality of physiological effects and that subsidiary efiects limit the clinical use of the hormones. It has been found that the compounds of this invention have an advantageous ratio of I desirable to undesirable activity.
- this invention provides a novel and inexpensive method for producing halogen derivatives of important steroids.
- the compounds of this invention are 3-keto-4-halo-A steroids derived from 4-estrenes, 4-androstenes or 4-pregnenes.
- the compounds of this invention have the following structure:
- Aliphatic, aryl and aralkyl esters of the above compounds such as, for example, acetate, benzoate, propionate, phenylacetate and half-succinate esters are also in cluded within the scope of this invention.
- Such esters ' may, be obtained by utilizing the desired ester of the epoxy starting material or by the preferred method of reacting the 4-halo derivative with the desired acyl halide or anhydride in a tertiary amine such as pyridine.
- 3-keto-4,5-epoxysteroid has the following structural formula:
- the desired 4-halo end product can be obtained by treating a solution or suspension of the 4,5 epoxysteroid in a halogenated or oxygenated water immiscible solvent such as carbon tetrachloride, methylenechloride, chloroform or ether with hydrohalic acid such as, for example, hydrogen chloride or hydrogen bromide either as a solution in a solvent miscible with the solvent for the epoxy compound or as a gas bubbled through the reaction mixture.
- the solvent for the hydrohalic acid may be, for example, a ketone solvent such as acetone or a lower aliphatic alcohol such as methanol, ethanol or propanol.
- the epoxy compound may be dissolved in a water miscible solvent such as, for example, dioxane, acetic acid, propionic acid, acetone or ethanol and reacted with an aqueous or acetic acid solution of the hydrohalic acid.
- a water miscible solvent such as, for example, dioxane, acetic acid, propionic acid, acetone or ethanol
- the Zi-keto-4-halo-A steroid of this invention is ob tained from the'reaction mixture by use of ordinary isolation procedures well known to the art.
- the reaction mass may be diluted with water and the 3-keto-4-halo-A compound extracted with a suitable solvent such as, for example, methylene chloride, benzene, chloroform or ether.
- a suitable solvent such as, for example, methylene chloride, benzene, chloroform or ether.
- the solvent extract is washed with water, dried and concentrated to a crystalline
- the end product can be recrystallized from an alcohol such -as,'for example, ethanol or from a mixture of solvents, such as methylene chloride-pentane.
- the epoxy starting materials of Formula 2 are readily prepared by treating a 3-ket'o-A '-steroid compound of the 4-estrene, 4-androstene, or 4-pregnene series in a watermiscible solvent with an alkaline hydrogen peroxide aqueoussolution. This reaction is shown in the following scheme, in which R R2 and R are as-given abover;
- the reaction is preferably carried out until the major proportion of the starting material has been expoxidized.
- the course of the reaction will be checked spectrophotometrically and thereaction mixture quenched preferably with cold water immediately after the disappearance of unsaturation in ring A, which is indicated by the disappearance of the characteristic cap-unsaturated ketone absorption in the 238 -m -242 mp. region.
- the desired 4,5 epoxy com'pounds are obtained by filtration or by solvent extraction.
- Example III.-4-chl0r0test0ster0ne To a solution of 1.0 g. of 4,5-epoxytestosterone (stereoisomeric. mixture) in 10 ml. of glacial acetic acid was added 2 ml. of an 8% hydrogen chloride in acetic acid solution. The reaction was kept for 12 hours at room temperature, then diluted cautiously with water to induce crystallization. The precipitate was removed by filtration and dried yielding 1.04 g. of 4-chlorotestosterone,
- Example V.4-br0mopr0gester0ne One. gram of 4,5-epoxyprogesterone (stereoisomeric mixture) was dissolved in 10 ml. of purified dioxane and 2 ml. of 48% hydrobromic acid were added. 'The reaction, was kept at 25 C. .for 3.6 hours with occasional swirling, then was diluted with 75 ml; of water. The precipitated solid was filtered and washed well with V Crystallization from -methylene chloride-ether afforded 0.7 g. of 4-brom0progesterone, 178-180," C., 1 3 1110900, which .gave no depression on .melting with that of Example'lV.
- Example X .-4-br0m0-19-n0rtest0sterone One gram of 4,5-epoxy-19-nortestosterone was dissolved in ml. of glacial acetic acid and the solution cooled to C. One ml. of a hydrogen bromide in acetic acid solution was added and the solution kept at 15 C. for one hour. Dilution with water afforded a precipitate which was extracted with benzene, washed with water and dried. The benzene extract upon concentration yielded 100 mg. of 4-bromo-19-nortestosterone, M.P.
- Example XI.-4-bromo-19-n0rtest0ster0ne benzoate A solution of 1.5 g. of 4,5-epoxy-l9-nortestosterone benzoate (stereoisomeric mixture) in 20 ml. of acetic acid was cooled in an ice bath and treated with 2 ml. of 27% hydrogen bromide in acetic acid for 20 minutes. The reaction was diluted with water and the bromo compound extracted with methylene chloride. The methylene chloride extract was washed with water, sodium bicarbonate solution and water. The solution was concentrated in vacuo and the product crystallized from ether. The yield of product, M.P. 118-122" C.
- Example XIII .4-br0mo-1 7a-methyltcstosterone A solution of 4 g. of 4,5-epoxy-17a-methyltestosterone (stereoisomeric mixture) in 50 ml. of glacial acetic acid was cooled in an ice bath. A saturated solution of hydrogen chloride in glacial acetic acid was added. The mixture was allowed to come to room temperature and to; stand for 24 hours with occasional swirling. The desired 4-bromo-l7e-methyltestosterone was isolated by quenching in water, filtering and washing well with water. A characteristic unsaturated ketone absorption on the crude product was observed spectrophotometrically.
- Example XIV.4-chIorotestosterone-I 7-acemte A solution of 1.2 g. of 4,5-epoxytestosterone-l7-acetate, M.P. 132-135 C., in 40 ml. of dimethylformamide was mixed with a solution of one equivalent of collidine hy drochloride in 5 ml. of dimethylformarnide. The reaction mixture was heated at 80 to 90 C. for ten hours. After quenching in water, extracting with chloroform and washing with water and dilute acid, the desired crude compound as indicated by ultraviolet absorption was obtained.
- Example XV One gram of 4-bromotestosterone in 4 ml. of pyridine was reacted with 0.3 g. of succinic anhydride at room temperature for two days. The reaction mixture was quenched carefully with Water to separate the desired 17-succinate half ester after washing well with water and air drying. A satisfactory E was noted on the ultraviolet spectrum.
- Example X VI.4-br0mo2estosterone A solution of 0.5 g. of 4,5-epoxytestosterone (stereoisomeric mixture) in dry ether was saturated with hydrogen bromide gas several times over a period of twelve hours at room temperature. The excess acid was removed from wherein X is a member selected from the group consisting of bromo and chloro; R is a member selected from the group consisting of hydrogen and methyl; when R is hydrogen R is a member selected from the group consisting l :H and and when R, is methyl R is a member selected from the group consisting of on 00 on. OH
- X is a member selectedfrom the group consisting of bromo and chloro;
- R is a member selected from the ro pv consis ing of hydrogen and methyl;
- R1 is drogen
- R is a member selected from the, group consisting of and v CHI and hen 1 s me hyl R3 a member elected from V the group consisting of 0H coon ⁇ 01-1 4 4 6 n rt "on;
- cocmorr which comprises reacting a .3-keto-4,5-epoxy steroid having the following formula:
Description
'3-KETO-4-HALO-A STEROID Percy L. Julian, Oak Park, and Helen C. Printy, Chicago, Ill., assignors to The Julian Laboratories, Inc., Franklin, Park, 111., a corporation of Illinois No Drawing. Application December '21, 1955 Serial No. 554,419
17 Claims. 7 (Cl. 260--397.3)
This invention relates to new steroid compounds and the method of preparing them. More particularly, it relates to certain physiologically active 3-lreto-4-halo-A' compounds and the method of preparing them. The invention provides 4-halo derivatives of active androgenic, anabolic, progestational and corticoid hormones.
The components of this invention have hormone activity and, more specifically, variously have advantageous anabolic, androgenic, progestational and cortical activity with minimal side efiects. It is well known that the active steroid hormones normally exhibit a plurality of physiological effects and that subsidiary efiects limit the clinical use of the hormones. It has been found that the compounds of this invention have an advantageous ratio of I desirable to undesirable activity.
In addition, this invention provides a novel and inexpensive method for producing halogen derivatives of important steroids.
The compounds of this invention are 3-keto-4-halo-A steroids derived from 4-estrenes, 4-androstenes or 4-pregnenes. Advantageously the compounds of this invention have the following structure:
FORMULA 1 in which:
I I I R is hydrogen or methyl, R; is C!=O, ([311; or OH-(])H and x is halogen, preferably chlorine or bromine.
Aliphatic, aryl and aralkyl esters of the above compounds such as, for example, acetate, benzoate, propionate, phenylacetate and half-succinate esters are also in cluded within the scope of this invention. Such esters 'may, be obtained by utilizing the desired ester of the epoxy starting material or by the preferred method of reacting the 4-halo derivative with the desired acyl halide or anhydride in a tertiary amine such as pyridine.
The method in accordance with this invention comg 2 acid or the hydrqhalig salt of a tertiary amine to obtain the corresponding 3-keto-4'-halo-A*- steroid. 3-keto-4,5-epoxysteroid has the following structural formula:
FORMULA 2 in which R R and R are as given above. It will be understood that the above structure includes the 411,50:- ep'oxides and the 45,5}9-epoxides, the bonds indicated by the solid lines in the 4 and 5 positions and connected to the oxygen not specifically indicating the isomeric form but rather being intended to include both the alpha and beta forms in the formula as given above and where used hereinafter, including in the claims. Since it is known to the art that epoxy compounds react with a hydrohalic acid to give the related halohydrins, it is surprising that the method in'accordance with this invention produces halogen-containing olefins under comparable conditions.
More specifically, the desired 4-halo end product can be obtained by treating a solution or suspension of the 4,5 epoxysteroid in a halogenated or oxygenated water immiscible solvent such as carbon tetrachloride, methylenechloride, chloroform or ether with hydrohalic acid such as, for example, hydrogen chloride or hydrogen bromide either as a solution in a solvent miscible with the solvent for the epoxy compound or as a gas bubbled through the reaction mixture. The solvent for the hydrohalic acid may be, for example, a ketone solvent such as acetone or a lower aliphatic alcohol such as methanol, ethanol or propanol. Alternatively, the epoxy compound may be dissolved in a water miscible solvent such as, for example, dioxane, acetic acid, propionic acid, acetone or ethanol and reacted with an aqueous or acetic acid solution of the hydrohalic acid. In the case of both methods it is preferred to maintain the temperature of the reaction fluid from about 0 C. to about 35 C. for from about t 10 minutes to several days.
, mass.
- prises treating a 3-keto-4,5-epoxysteroid with a hydrohalic mide, collidine hydrochloride or a-picoline hydrobromide.
The Zi-keto-4-halo-A steroid of this invention is ob tained from the'reaction mixture by use of ordinary isolation procedures well known to the art. Thus, for example, the reaction mass may be diluted with water and the 3-keto-4-halo-A compound extracted with a suitable solvent such as, for example, methylene chloride, benzene, chloroform or ether. The solvent extract is washed with water, dried and concentrated to a crystalline If desired, the end product can be recrystallized from an alcohol such -as,'for example, ethanol or from a mixture of solvents, such as methylene chloride-pentane. The epoxy starting materials of Formula 2 are readily prepared by treating a 3-ket'o-A '-steroid compound of the 4-estrene, 4-androstene, or 4-pregnene series in a watermiscible solvent with an alkaline hydrogen peroxide aqueoussolution. This reaction is shown in the following scheme, in which R R2 and R are as-given abover;
CH: CH:
Rs R:
R! l R1 H30: A Alkali mixture with a major proportion ofja lower aliphatic alcohol such as methanol or ethanol are satisfactory- The reaction will be carried out at a low temperature,
preferably from'a-bout -20 'C. to about 30 C. and advantageously from about -20 C. to +10 C.
The reaction is preferably carried out until the major proportion of the starting material has been expoxidized. Advantageously the course of the reaction will be checked spectrophotometrically and thereaction mixture quenched preferably with cold water immediately after the disappearance of unsaturation in ring A, which is indicated by the disappearance of the characteristic cap-unsaturated ketone absorption in the 238 -m -242 mp. region. The
quenching at this state of the reaction insures the avoid- I 'ance. of further undesired oxidation to acidic products. The desired 4,5 epoxy com'pounds are obtained by filtration or by solvent extraction.
assault) r gave no depression when melted with the 4-bromotestosterone described in Example 1.
Example III.-4-chl0r0test0ster0ne To a solution of 1.0 g. of 4,5-epoxytestosterone (stereoisomeric. mixture) in 10 ml. of glacial acetic acid was added 2 ml. of an 8% hydrogen chloride in acetic acid solution. The reaction was kept for 12 hours at room temperature, then diluted cautiously with water to induce crystallization. The precipitate was removed by filtration and dried yielding 1.04 g. of 4-chlorotestosterone,
- MP. 210-218 C. Recrystallization from methylene chloride-pentane. afforded. glistening prisms, M.P. 215- The epoxy starting materials of .Formula '2 and the 7 'method of their preparation are fiully 'set forth inour copendingpatent application, Serial No. "486,014, filed February 3, 1955, the-disclosure' of which-is incorporated herewith. Reference may be madev to said application, Serial No; 486,014, for specific examples ofsaid epoxy starting =materials as well as: for specific detail-as to the method of their preparation.
The compounds of this invention and the method of' their preparation will be more specifically illustratedhy the following examples; "Our copending patent application, SerialNo. 486,014, specifically illustrates the. pre aration of the starting material usedin each ofithefollowing examples.-
Example I 4-bro'motestosterone A solution of' 0l5 g. of 4,5-'epoxytestosterone, 'M.P. 138-140" C.,'was dissolved in 5 ml. of glacial 'aceticjaci'd and cooled to 15 C 'One milliliter of 30% hydrogen bromidein; acetic acidwas added and the reaction kept at 10-l5 C. for 30'minut'es. The solution was poured withstirring into 200 m1. of water, and the'precipitated solidw'as collectedby filtration. The product, 4-broniotestosterone, M.P.'l52- -15,4 C. 'hadan absorption maximumat 261 mp=11,600,fand"weighed 590 mg.
When 05 g. of the isomeric 4,5-epoxytestost erone, M.P.- 152-155 C., was treated in the manner described in Example I, 0.58 g. ofthe identical 4-bromo-testoster- --one,- M.P. 155'157 C.,- E -1-1,800 was obtained; This water.
Example lV.-?4-bromoprogesterone One gram of 4,5-epoxyprogesterone (stereoisomeric mixture) was dissolved in 10 ml. of glacial acetic acid and the solution cooled to 15 C. To the cooled solution, 1 ml. of a 30% hydrogen bromide in acetic acid solution was added, and the reaction kept at 15 C. for 20, minutes. The solution was poured into 200 ml. of water and the precipitated product collected by filtration. The product, 1.18 g. of 4-brom0progesterone, was crystallized from methylene chloride-pentane to give glistening prisms, M.P. 170-172 C. dec., E =9,000.
Example V.4-br0mopr0gester0ne One. gram of 4,5-epoxyprogesterone (stereoisomeric mixture) was dissolved in 10 ml. of purified dioxane and 2 ml. of 48% hydrobromic acid were added. 'The reaction, was kept at 25 C. .for 3.6 hours with occasional swirling, then was diluted with 75 ml; of water. The precipitated solid was filtered and washed well with V Crystallization from -methylene chloride-ether afforded 0.7 g. of 4-brom0progesterone, 178-180," C., 1 3 1110900, which .gave no depression on .melting with that of Example'lV.
Example VI.4-chl0r 0pr0 gesterone To one gram of 4,5-epoxyprogesterone (stereoisomeric mixture) dissolved in 10 ml. of glacial acetic acid, 1 m1. of a 25% solution of hydrogen chloride in acetic acid was added. The reaction mixture was kept at room temperature for 15 hours, during which time crystals of 4- chloroprogesterone came out. The crystals, 410 mg, were collected by filtration. They melted at 205213 C., and had an absorp'tionmaximum at 255 mp.=l3,000. A second crop of material, 540 mg. melting at 2092l5 C., E =11,000 was obtained from the mother liquor.
Example VIl.4-bromoa'es0xycorticosterone Three grams of 4,5-epoxydesoxycorticosterone (stereoisomeric mixture) and 5 g. of pyridine hydrobromide were refluxed for Zhours in 50 ml. of anhydrous ethanol. The solution was then concentrated to remove the sol- Vent, diluted with water and extracted with methylene chloride. The methylene chloride extract was washed with water, dried and concentrated to a crystalline mass. Upon recrystallization from ethanol, 4sbromodesoxycorticosterone,M.P. 173-175 C., E mp=12,200.
Example VIII. 4-br0m0cortis0ne A solution of 1.0 g. of cortisone oxide (stereoisomeric mixture) in 10 ml. of methylene chloride was cooled to 5 C.,and 2'ml. st 30% "hydrogen bromide zin acetic acid Wasadded. The' reaction 'was=he ld:at 5-10 C. for
30 minutesg then was pourediinto iml. ofwater and extraeted'with'additional methylene chloride. Themeth- 'yl-ene chloride-extract waswashed free of acid =and:dried. 'Removal of solvent aflorded 4-bromocortisone as a'pale yellow flufffE g dfitlo. I
Example IX.4-br0mohydrocortistme A solution of lg. of 4;5-epoxyhydrocortisone (stereoisomr ric mixture) in 10 ml. of chloroform was cooled to C. and treated for 30 minutes at 5-10 C. with 2 ml. of 30% hydrogen bromide in acetic acid. Upon working up the reaction, 4-bromohydrocortisone was obtained as a yellow fluff, E mp=9,000.
Example X .-4-br0m0-19-n0rtest0sterone One gram of 4,5-epoxy-19-nortestosterone was dissolved in ml. of glacial acetic acid and the solution cooled to C. One ml. of a hydrogen bromide in acetic acid solution was added and the solution kept at 15 C. for one hour. Dilution with water afforded a precipitate which was extracted with benzene, washed with water and dried. The benzene extract upon concentration yielded 100 mg. of 4-bromo-19-nortestosterone, M.P.
125-128 C., dec., E =8,000.
Example XI.-4-bromo-19-n0rtest0ster0ne benzoate A solution of 1.5 g. of 4,5-epoxy-l9-nortestosterone benzoate (stereoisomeric mixture) in 20 ml. of acetic acid was cooled in an ice bath and treated with 2 ml. of 27% hydrogen bromide in acetic acid for 20 minutes. The reaction was diluted with water and the bromo compound extracted with methylene chloride. The methylene chloride extract was washed with water, sodium bicarbonate solution and water. The solution was concentrated in vacuo and the product crystallized from ether. The yield of product, M.P. 118-122" C. dec., E m =l3,000 was Example XII.4-brom0-19-n0rtestoster0ne b enzoate One gram of crude 4,5-epoxy-l8-nortestosterone benzoate (stereoisomeric mixture) was dissolved in 15 ml. of
anhydrous ether, cooled, and stirred for 20 minutes with 2 m1. of 27% hydrogen bromide in acetic acid. Upon working up as described in the previous example, 420 mg.
'of 4-bromo-l9-nortestosterone benzoate, M.P. ll8120 C. dec., E m =12,000 was obtained.
Example XIII .4-br0mo-1 7a-methyltcstosterone A solution of 4 g. of 4,5-epoxy-17a-methyltestosterone (stereoisomeric mixture) in 50 ml. of glacial acetic acid was cooled in an ice bath. A saturated solution of hydrogen chloride in glacial acetic acid was added. The mixture was allowed to come to room temperature and to; stand for 24 hours with occasional swirling. The desired 4-bromo-l7e-methyltestosterone was isolated by quenching in water, filtering and washing well with water. A characteristic unsaturated ketone absorption on the crude product was observed spectrophotometrically.
Example XIV.4-chIorotestosterone-I 7-acemte A solution of 1.2 g. of 4,5-epoxytestosterone-l7-acetate, M.P. 132-135 C., in 40 ml. of dimethylformamide was mixed with a solution of one equivalent of collidine hy drochloride in 5 ml. of dimethylformarnide. The reaction mixture was heated at 80 to 90 C. for ten hours. After quenching in water, extracting with chloroform and washing with water and dilute acid, the desired crude compound as indicated by ultraviolet absorption was obtained.
Example XV One gram of 4-bromotestosterone in 4 ml. of pyridine was reacted with 0.3 g. of succinic anhydride at room temperature for two days. The reaction mixture was quenched carefully with Water to separate the desired 17-succinate half ester after washing well with water and air drying. A satisfactory E was noted on the ultraviolet spectrum.
Example X VI.4-br0mo2estosterone A solution of 0.5 g. of 4,5-epoxytestosterone (stereoisomeric mixture) in dry ether was saturated with hydrogen bromide gas several times over a period of twelve hours at room temperature. The excess acid was removed from wherein X is a member selected from the group consisting of bromo and chloro; R is a member selected from the group consisting of hydrogen and methyl; when R is hydrogen R is a member selected from the group consisting l :H and and when R, is methyl R is a member selected from the group consisting of on 00 on. OH
H H, o H;
and
c o CHiOH 2. 4-chloroprogesteronef 3. A compound having the formula wherein R is selected from the group consisting of hydrogen and acyl.
4. 4-chlorotestosterone-17-acetate.
5. 4-chlorotestosterone.
6. 4-bromotestosterone.
7. A compound having the formula wherein X is a member selected from the group consisting of bromo and chloro.
8, 4wbromo-17 methyltestosterone 9. A, on pqunih vingtheio mula I i on wherein X is a member selected from the group consisting of bromo and chloro and R is selected from the group consisting of hydrogen and acyl.
10. 4-bromo-19-n01'tcs1osterone.
11. 4-bromo-19-nortestosteroue benzoate.
12. 4-bromocortisone.
13. 4-bromohydrocortisqne.
14. 4-bromodesoxycorticosterone.
15. The process of preparing a steroid having the folpwiu ru tura tormula:
wherein X is a member selectedfrom the group consisting of bromo and chloro; R is a member selected from the ro pv consis ing of hydrogen and methyl; when R1 is drogen R is a member selected from the, group consisting of and v CHI and hen 1 s me hyl R3 a member elected from V the group consisting of 0H coon} 01-1 4 4 6 n rt "on;
and
cocmorr which comprises reacting a .3-keto-4,5-epoxy steroid having the following formula:
35 References Cited in the file of this patent UNITED STATES PATENTS Archer June 15, 1954 Colton Dec. 20, 1955 oTHER REFERENCES Bremen Congress Handbook, XIVth Internat. Congr. 5 Pure and Applied Chemistry, (Zurich, Switz.: Berichthaus Zurich, July 21, 1955), pages 162 and 163.
Inhofien Apr. 28, 1942
Claims (1)
1. A COMPOUND HAVING THE FOLLOWING BASIC STRUCTURAL FORMULA:
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| Application Number | Priority Date | Filing Date | Title |
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| US554419A US2933510A (en) | 1955-12-21 | 1955-12-21 | 3-keto-4-halo-delta 4, 5 steroid |
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| Application Number | Priority Date | Filing Date | Title |
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| US554419A US2933510A (en) | 1955-12-21 | 1955-12-21 | 3-keto-4-halo-delta 4, 5 steroid |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2953582A (en) * | 1956-04-23 | 1960-09-20 | Farmaceutici Italia | 4-chloro-adrenosterone |
| US3030390A (en) * | 1957-12-24 | 1962-04-17 | Farmaceutica Italia Soc | Process for the preparation of 4, 17-alpha-dihydroxy-progesterone and its esters |
| US3082221A (en) * | 1956-09-17 | 1963-03-19 | Syntex Corp | 4-chloro-6alpha-methyl derivatives of testosterone |
| US3127424A (en) * | 1955-04-27 | 1964-03-31 | British Drug Houses Ltd | 4-chloro-3-oxo-delta-steroids of the androstane and pregnane series and process therefor |
| US3146239A (en) * | 1957-09-23 | 1964-08-25 | Syntex Corp | 4-halo-19-nor-progesterone |
| US3154542A (en) * | 1962-06-18 | 1964-10-27 | British Drug Houses Ltd | 4-acylthio and 4-aroylthio derivatives of 3-keto-delta4-steroids and process for preparing same |
| US3309398A (en) * | 1964-08-31 | 1967-03-14 | Smith Kline French Lab | 4-halo and 4-oxygenated-b-nortestosterones and b-norprogesterones |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2280828A (en) * | 1936-09-29 | 1942-04-28 | Schering Corp | Process for the manufacture of compounds of the cyclopentanopolyhydrophenanthrene series |
| US2681353A (en) * | 1952-03-11 | 1954-06-15 | Sterling Drug Inc | Chlorination of keto-steroids |
| US2727912A (en) * | 1954-08-20 | 1955-12-20 | Searle & Co | 4,5-dihydroxypregnanes |
-
1955
- 1955-12-21 US US554419A patent/US2933510A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2280828A (en) * | 1936-09-29 | 1942-04-28 | Schering Corp | Process for the manufacture of compounds of the cyclopentanopolyhydrophenanthrene series |
| US2681353A (en) * | 1952-03-11 | 1954-06-15 | Sterling Drug Inc | Chlorination of keto-steroids |
| US2727912A (en) * | 1954-08-20 | 1955-12-20 | Searle & Co | 4,5-dihydroxypregnanes |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3127424A (en) * | 1955-04-27 | 1964-03-31 | British Drug Houses Ltd | 4-chloro-3-oxo-delta-steroids of the androstane and pregnane series and process therefor |
| US2953582A (en) * | 1956-04-23 | 1960-09-20 | Farmaceutici Italia | 4-chloro-adrenosterone |
| US3082221A (en) * | 1956-09-17 | 1963-03-19 | Syntex Corp | 4-chloro-6alpha-methyl derivatives of testosterone |
| US3146239A (en) * | 1957-09-23 | 1964-08-25 | Syntex Corp | 4-halo-19-nor-progesterone |
| US3030390A (en) * | 1957-12-24 | 1962-04-17 | Farmaceutica Italia Soc | Process for the preparation of 4, 17-alpha-dihydroxy-progesterone and its esters |
| US3154542A (en) * | 1962-06-18 | 1964-10-27 | British Drug Houses Ltd | 4-acylthio and 4-aroylthio derivatives of 3-keto-delta4-steroids and process for preparing same |
| US3309398A (en) * | 1964-08-31 | 1967-03-14 | Smith Kline French Lab | 4-halo and 4-oxygenated-b-nortestosterones and b-norprogesterones |
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