WO1995030684A1 - SYNTHESIS OF 17β-CYANO-3-ETHOXY-17α-HYDROXY-6-METHYLANDROSTA-3,5,9(11)-TRIENE - Google Patents
SYNTHESIS OF 17β-CYANO-3-ETHOXY-17α-HYDROXY-6-METHYLANDROSTA-3,5,9(11)-TRIENE Download PDFInfo
- Publication number
- WO1995030684A1 WO1995030684A1 PCT/US1995/005026 US9505026W WO9530684A1 WO 1995030684 A1 WO1995030684 A1 WO 1995030684A1 US 9505026 W US9505026 W US 9505026W WO 9530684 A1 WO9530684 A1 WO 9530684A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cyano
- methylandrosta
- ethyl ether
- triene
- dihydroxy
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
-
- 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
-
- 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
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
Definitions
- the present invention is a chemical process for the transformation of a 17- keto steroid to the corresponding 17 ⁇ -cyano-17 ⁇ -hydroxy steroid.
- EXAMPLES 1 and 25 discloses a process for the transformation of a ⁇ 4 -3,17-diketo steroid without substitution at C 6 .
- EXAMPLE 2 discloses a process for the transformation of a ⁇ ' 9(11 ⁇ -3,17-diketo steroid without substitution at C g .
- EXAMPLE 26 discloses a process for the transformation of a ⁇ 1,4 -3,17-diketo steroid without substitution at Cg.
- EXAMPLE 27 discloses a process for the transformation of a 6 ⁇ -methyl-ll ⁇ -hydroxy- ⁇ 4 -3,17- diketo steroid.
- EXAMPLE 28 discloses a process for the transformation of a 6 ⁇ - methyl- ⁇ 1,4 -3,17-diketo steroid.
- These patents also disclose 17 ⁇ -cyano-3,17 ⁇ - dihydroxy-5-ene 3-ethylidine ketal ethers (EXAMPLE 3) and 17 ⁇ -cyano-3,17 ⁇ - dihydroxy-3,5-diene 3-methyl ethers (EXAMPLE 24).
- EXAMPLE 3 17 ⁇ -cyano-3,17 ⁇ - dihydroxy-5-ene 3-ethylidine ketal ethers
- EXAMPLE 24 17 ⁇ -cyano-3,17 ⁇ - dihydroxy-3,5-diene 3-methyl ethers
- US Patent 4,921,638 discloses 17 ⁇ -cyano-3,17 ⁇ -dihydroxyandrosta-3,5,9(ll)- triene 3-methyl ether (Preparation 1) and 17 ⁇ -cyano-6-fluoro-3,17 ⁇ - dihydroxyandrosta-3,5,9(ll)-triene 3-methyl ether (Preparation 5).
- US Patent 4,921,638 (EXAMPLE 89) discloses the production of 17 ⁇ -cyano-9 ⁇ ,17 ⁇ - dihydroxyandrost-4-en-3-one from the corresponding 17-keto steroid using potassium cyanide, sulfuric acid, methanol and water. J. Am. Chem.
- Soc, 75, 650 (1953) discloses the preparation of the 17- cyanohydrin of androst-4-ene-3,17-dione and its conversion to the corresponding 3- enol ethyl ether, the 3-enol benzyl ether and the 3-ethylene glycol ketal.
- Helv. Chem. Ada, 33, 1093 (1950) discloses the preparation of 17 ⁇ -cyano- 3,17 ⁇ -dihydroxyandrost-5-ene 3-acetyl ester.
- Helv. Chim. Ada, 29, 1580 (1946) discloses the preparation of a mixture of
- Helv. Chim. Ada, 21, 1317 (1938) discloses 3-acetoxyandrost-5-en-17-one to the 17- spirohydantoin using hydrogen cyanide.
- Steroids, 28, 89 (1976) discloses the preparation of the 17-cyanohydrin of androstenedione. The stereochemistry of the cyanohydrin was not determined.
- US Patent 3,496,169 discloses the preparation of the ⁇ -cyanohydrin from carbonyl compounds using alkylcyanoaluminum compounds.
- East German Patent 147,669 discloses the preparation of a 17 ⁇ -hydroxy-17 ⁇ - cyano steroids by reaction of a 17-keto-steroid with an alkanone or a cycloalkanone cyanohydrin in the presence of a base.
- the steroid had a double bond at 4,5-, 5,6- and 5,10- positions.
- the 3-position was a ketone, acetoxy or dimethoxyketal.
- Japanese Patent J5 7,062,296 discloses preparation of 17 ⁇ - hydroxyprogesterone derivatives from 17 ⁇ -cyano-17 ⁇ -hydroxyandrost-4-en-3-one or 17 ⁇ -cyano-17 ⁇ -hydroxyandrosta-4,9(ll)-dien-3-one in which the 3-carbonyl and 17 ⁇ - hydroxy groups are protected.
- Japanese Patent J5 7,062,299 discloses the preparation of 17 ⁇ -cyano-17 ⁇ - hydroxyandrost-4-ene and 17 ⁇ -cyano-17 ⁇ -hydroxyandrosta-4,9(ll)-diene or their 3- acetal derivatives by use of either hydrogen cyanide or an alkali metal salt thereof.
- Japanese Patent J5 7,062,300 discloses 17 ⁇ -cyano-17 ⁇ -hydroxyandrost-4-en-3- one and 17 ⁇ -cyano-17 ⁇ -hydroxyandrosta-4,9(ll)-dien-3-one and the 3-acetals thereof.
- US Patent 4,977,255 discloses an important process for the transformation of 17 ⁇ -cyano-17 ⁇ -hydroxy steroids into commercially important corticoids or progesterones.
- the 17 ⁇ -cyano-17 ⁇ -hydroxy steroid starting materials were prepared in PREPARATIONS 1 thru 10.
- Some of the 17-keto steroids used to make the 17 ⁇ - cyano-17 ⁇ -hydroxy steroids contained methyl substitution at Cg (PREPARATIONS 3 and 4), methylene substitution at Cg (PREPARATION 8), ⁇ 9(11) -unsaturation in the C-ring (PREPARATIONS 1, 5, 9 and 10) and/or a 3-methoxy- ⁇ 3 ' 5 -unsaturated A-ring (PREPARATIONS 1, 2 and 5).
- Tetrahedron Letters, 31 3669( 1990) discloses the preparation of 17 ⁇ -cyano- 3,17 ⁇ -dihydroxyandrosta-3,5,9(ll)-triene and its conversion to hydrocortisone acetate.
- US Patent 5,003,063 discloses the conversion of protected cyanohydrins (II) to the corresponding protected 21-halo steroid (IV) where the protecting groups are at C 3 . None of the steroids exemplified had a substituent at Cg other than a ⁇ 5 ⁇ - double bond.
- CA: 106:84943 and CA 109:170717 disclose 3-hydroxyandrosta-3,5,9(ll)-trien- 17-one 3-ethyl ether which does not contain the methyl group at Cg which is necessary to produce the 6-methyl intermediate.
- the process of the present invention is the transformation of 3-hydroxy-6- methylandrosta-3,5,9(ll)-trien-17-one 3-ethyl ether (I) to 17 ⁇ -cyano-3,17 ⁇ -dihydroxy- 6-methylandrosta-3,5,9(ll)-triene 3-ethyl ether (II) by reaction with cyanide in the presence of an acid and a suitable solvent.
- 3-ethyl ether starting material 3-hydroxy-6-methylandrosta-3,5,9(ll)- trien-17-one 3-ethyl ether (I) is prepared from 6 ⁇ -methylandrost-4,9(ll)-diene-3,20- dione (US Patent 2,842,573, EXAMPLE 2) by reaction with triethylorthoformate in a suitable solvent such as ethanol in the presence of pyridine hydrochloride under a nitrogen atmosphere. The reaction is heated at about 40° until the reaction is complete as monitored by TLC using a methylene chloride/acetone (97.5/2.5) solvent system (a triethylamine quench is necessary before performing the TLC). The reaction is complete when only a few percent of starting material is left.
- the reaction mixture is cooled to 20-25° and the desired 3-ethyl ether crystallizes out. If some 3-hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3- ethyl ether (I) is available, it is preferred to seed the cooled reaction mixture.
- the 3- ethyl ether (I) must be crystallized slowly to assure good filtration. If the 3-ethyl ether (I) comes out of solution too fast, very fine particles are formed resulting in a poor filtration. To avoid this, crystallization prior to water addition is necessary. It is best induced by seeding. When a thick slurry is obtained, the mixture is cooled further on an ice bath.
- the 3-hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3-ethyl ether (I) is contacted with hydrogen cyanide at a pH of about 7 to about 11. It is critical to maintain the pH of the reaction mixture in the operable range of about 7 to about 11, preferably from about 8 to about 10, more preferred is from about 9.0 to about 9.5. The pH is conveniently set in this range by using a slight excess of cyanide salt relative to acid (10-25%).
- the hydrogen cyanide is conveniently prepared in situ by combining a salt of cyanide amount of an acid with a pK a of less than about 7; it is preferred that the pK g be less than 6. It is preferred that the cyanide initially be either sodium or potassium cyanide however since it is preferred to add it as an aqueous solution the particular form of the cyanide is not important as long as it is soluble.
- the acid is necessary to convert the cyanide (C ⁇ N " ) to hydrogen cyanide (H-C ⁇ N) which is the active species in the formation of the 17-cyanohydrin. It is preferred that the acid be a carboxylic acid.
- Suitable acids include inorganic acids such as hydrochloric, hydrobromic, hydriodic, sulfuric, hydrofluoric, perchloric, nitric and phosphoric; carboxylic acids such as acetic acid, formic, propionic, benzoic, chloroacetic, dichloroacetic, trichloroacetic, pivalic, ethylhexanoic and other organic acids such as p-TSA, methanesulfonic and camphorsulfonic or their equivalent.
- the particular acid is not important as long as it is sufficiently acidic to transform the cyanide (C ⁇ N " ) to hydrogen cyanide (H-C ⁇ N).
- the hydrogen cyanide may be contributed by a labile cyanohydrin compound such as acetone cyanohydrin which is commercially available and commonly used for this purpose.
- the nature of the solvent or solvent mixture is critical.
- the solvent or solvent system must be such that the 17 ⁇ -cyano-3,17 ⁇ - dihydroxy-6-methylandrosta-3,5,9(ll)-triene 3-ethyl ether (II) is less soluble in the reaction mixture than the 17 ⁇ -cyano isomer.
- the 3-hydroxy-6-methylandrosta- 3,5,9(ll)-trien-17-one 3-ethyl ether (I) steroid starting material and cyanide salt must have at least some solubility in the solvent or solvent mixture.
- the solvent can be adjusted during the reaction, if necessary, to cause more product to precipitate. It is preferred that the solvent or solvent mixture contain at least 50% of an alcohol.
- the alcohol be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, t-butanol, ethylene glycol and propylene glycol.
- the preferred alcohol is methanol.
- Suitable non- alcoholic solvents include water, methylene chloride, toluene, tetrahydrofuran or mixture thereof.
- the reaction should be performed in a temperature range of from about 0° to about 70° (in a sealed system); preferable from about 10° to about 45°; more preferably from about 20° to about 40°. At elevated temperatures a sealed system is necessary to prevent the hydrogen cyanide from being distilled off. It is preferred to run the reaction for about one hour at about 30-35°, then reduce the temperature to about 20-25°.
- reaction is quenched with (acetic) acid to a pH of less than 7. At this point the reaction is warmed to about 50° and THF is added until all the solids dissolve. It is important to note that at this point large amounts of hydrogen cyanide are evolved. When all the solids have dissolved, water is added over a period of about three minutes. If it is added to fast, the crystals will be too small and filtration and washing and drying will be more difficult.
- 17 ⁇ -Cyano-3, 17 ⁇ -dihydroxy-6-methylandrosta-3,5,9( 1 l)-triene 3-ethyl ether (II) is equivalent to hydrates and solvates thereof.
- 17 ⁇ -Cyano-3,17 ⁇ -dihydroxy-6-methylandrosta-3,5,9(ll)-triene 3-ethyl ether (II) is useful in the production of 6-methyl steroids such as methylprednisolone, see US Patents 4,500,461, 4,548,748 and 4,977,255.
- TLC refers to thin-layer chromatography.
- HPLC refers to high pressure liquid chromatography.
- THF refers to tetrahydrofuran. When solvent pairs are used, the ratios of solvents used are volume/volume (v/v).
- the ratio of the solid to the solvent is weight volume (wt v).
- Hydrogen cyanide refers to HCN (H-C ⁇ N).
- the starting material may be recovered by combining the mother liquors and the methanol washes and concentrating to reduce the volume to the point that most of the organic solvents are removed.
- Methanol 25 ml
- Hydrochloric acid (12 N, 5 ml) is added and the mixture is stirred.
- the precipitate is filtered and washed with water and cold methanol.
- PREPARATION 2 3-Hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3-methyl ether
- Rf 0.71 (methylene chloride/acetone, 97.5/2 5);
- HPLC R ⁇ . 5.56 min (acetonitrile water, 90/10, flow rate 1.5 ml min, column C18 Nucloesil).
- PREPARATION 3 3-Hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3-propyl ether
- HPLC R j . 8.52 min (acetonitrile/water, 90/10, flow rate 1.5 ml/min, column C18 Nucloesil).
- EXAMPLE 1 17 ⁇ -Cyano-3,17 ⁇ -dihydroxy-6-methylandrosta-3,5,9(ll)-triene 3- ethyl ether (II) 3-Hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3-ethyl ether (I, PREPARATION 1, 50 g), potassium cyanide (19.95 g) and methanol (120 ml) are combined and purged with a nitrogen/reduced pressure system (3 x) and heated to 35-40° in a sealed system. The vapors are removed under reduced pressure and acetic acid (14 ml) is added via a syringe.
- the vacuum is slowly release to nitrogen and once ambient pressure is reached the vessel is sealed.
- the reaction mixture is stirred for one hour at 35° and then at 20-25°.
- the reduced pressure is again replaced by nitrogen until ambient pressure is reached.
- Water (9 ml) is added and the mixture stirred for 30 min. If no solids are out of solution, the mixture is seeded.
- the flask is resealed and stirred at 25° until less than 3% starting material is observed by HPLC (usually overnight).
- the reaction is complete, the reaction mixture is vented with nitrogen and quenched with acetic acid (4 ml).
- the reaction is warmed to about 50° and THF (about 45 - 50 ml) is slowly added until all the solids are dissolved.
- the mixture is purged with nitrogen and subjected to reduce pressure.
- Acetic acid (3.0 ml) is added using reduced pressure in the flask.
- the reaction is maintained at 45-48°. After 1 hr 45 min, the mixture is seeded with the desired cyanohydrin obtained from previous experiments.
- the mixture After a total of four hours, the mixture is cooled. One hr later, the mixture is at 27° and a sample is taken. Analysis discloses about 9% of the starting material remains in the mixture. The supernatant is checked at the same time. Very little of the starting material is seen, indicating that the starting material coprecipitates ' with the product.
- the slurry is heated back up to 35° and stirred overnight. No change is noticed after the overnight stirring.
- the reaction is then quenched with acetic acid (1.5 ml) and the mixture is cooled to 25°.
- the solids are filtered off and washed with cold methanol.
- the crystals are analyzed by HPLC and found to contain about 8% starting material.
- the solids are then recrystallized by dissolving them in toluene/methanol.
- the assay on the crystals indicates that about 5-6% of starting material is still present. RecrystaUization does not remove the starting material.
- Tetrahydrofuran is added (10 ml) and the mixture is heated to 40°. Water is added to precipitate the product but an oU is observed. Methanol and seed crystals are added foUowing which crystals are obtained. The mixture is stirred slowly overnight, cooled and filtered. After washing (methanol/water) and drying, the title compound is obtained, 6.5 g yields.
- EXAMPLE 4 3-Hydroxy-6-methylandrosta-3,5,9(ll)-trien-17-one 3-ethyl ether
- the mixture is refluxed at 55 to 60° under nitrogen with stirring. When the steroid is in solution, the water bath is removed and the reaction mixture is aUowed to cool to 20-25°. Water (60 ml) is added over 30 minutes. When complete the mixture is cooled to 0 to 5° and stirred for 60 minutes. The mixture is filtered, washed with triethylamine (2% in cold (-5 to -10°) methanol, 60 ml) and dried to give the title compound.
- EXAMPLE 4 40 g), potassium cyanide (17.6 g) and methanol (96 ml) are mixed under nitrogen and stirred at 20-25°. Acetic acid (12.35 ml) is added and the mixture warmed to 35° with stirring. The reaction mixture is stirred at 35-40° for 45 minutes then cooled to 20-25°. Water (10.8 ml) is added and the mixture stirred untU the reaction is complete (as measured by HPLC). When the reaction is complete, the mixture is quenched with acetic acid (3.85 ml). When the reaction temperature is 20-25°, THF (20 ml) followed by water (20 ml) water is added and the mixture stirred for 5 min at 20-25° then cooled to -10° for 1-2 hr. The mixture is then filtered, washed with aqueous methanol (50%, 2 x 40 ml) at 10° and dried to give the title compound which because it is a temperature sensitive hydrate, is stored at ⁇ 0°. CHART A
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU23628/95A AU684946B2 (en) | 1994-05-09 | 1995-05-02 | SYNTHESIS OF 17B CYANO-3-ETHOXY-17a-HYDROXY-6-METHYLANDROSTA-3,5,9-(11)-TRIEN 9(11)-triene |
EP95917651A EP0759928A1 (en) | 1994-05-09 | 1995-05-02 | Synthesis of 17beta-cyano-3-ethoxy-17alpha-hydroxy-6-methylandrosta-3,5,9(11)-triene |
JP7528991A JPH10500946A (ja) | 1994-05-09 | 1995-05-02 | 17β−シアノ−3−エトキシ−17α−ヒドロキシ−6−メチルアンドロスタ−3,5,9(11)−トリエンの合成 |
MX9605428A MX9605428A (es) | 1994-05-09 | 1995-05-02 | SINTESIS DE 17 beta-CIANO-3-ETOXI-17ALFA-HIDROXI-6-METILANDROSTA-3,5,9(11)-T RIENO. |
KR1019960706331A KR970702873A (ko) | 1994-05-09 | 1996-11-08 | 17β-시아노-3-에톡시-17α-하이드록시-6-메틸안드로스타-3,5,9-트리엔의 합성 방법(SYNTHESIS OF 17β-CYANO-3-ETHOXY-17α-HYDROXY-6-METHYLANDROSTA-3,5,9-TRIENE) |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US24003694A | 1994-05-09 | 1994-05-09 | |
US08/240,036 | 1994-05-09 |
Publications (1)
Publication Number | Publication Date |
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WO1995030684A1 true WO1995030684A1 (en) | 1995-11-16 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US1995/005026 WO1995030684A1 (en) | 1994-05-09 | 1995-05-02 | SYNTHESIS OF 17β-CYANO-3-ETHOXY-17α-HYDROXY-6-METHYLANDROSTA-3,5,9(11)-TRIENE |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0759928A1 (ko) |
JP (1) | JPH10500946A (ko) |
KR (1) | KR970702873A (ko) |
CN (1) | CN1147816A (ko) |
AU (1) | AU684946B2 (ko) |
CA (1) | CA2187522A1 (ko) |
HU (1) | HUT75517A (ko) |
MX (1) | MX9605428A (ko) |
WO (1) | WO1995030684A1 (ko) |
Families Citing this family (1)
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CN112898365B (zh) * | 2021-03-08 | 2023-02-28 | 营口德瑞化工有限公司 | 一种17β-氰基-17α-羟基雄甾-4-烯-3-酮的合成方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2062641A (en) * | 1979-10-26 | 1981-05-28 | Roussel Uclaf | Anti inflammatory 17-chloroethynyl-11,17-dihydroxy androst-4-en-3-ones and derivatives thereof |
EP0153001A2 (en) * | 1984-02-03 | 1985-08-28 | The Upjohn Company | Steroids having an enamide or enimide group and their preparation |
WO1986000907A1 (en) * | 1984-07-23 | 1986-02-13 | Schering Aktiengesellschaft Berlin Und Bergkamen | Process for the manufacture of 6alpha-methyl steroids |
EP0181442A1 (de) * | 1984-09-17 | 1986-05-21 | Schering Aktiengesellschaft | Verfahren zur Herstellung von Pregnan-Derivaten |
EP0263569A2 (en) * | 1986-10-10 | 1988-04-13 | Roussel-Uclaf | 9-alpha-hydroxysteroids, process for their preparation and process for the preparation of the corresponding 9(11)-dehydro-derivatives. |
EP0268400A1 (en) * | 1986-11-05 | 1988-05-25 | The Upjohn Company | Steroidal 17alpha-silyl ethers and process to corticoids and progesterones |
DD281394A5 (de) * | 1984-12-10 | 1990-08-08 | Jenapharm Veb | Verfahren zur herstellung von steroid-c-17 alpha-carbonitrilen |
-
1995
- 1995-05-02 AU AU23628/95A patent/AU684946B2/en not_active Expired - Fee Related
- 1995-05-02 EP EP95917651A patent/EP0759928A1/en not_active Withdrawn
- 1995-05-02 CN CN95192975A patent/CN1147816A/zh active Pending
- 1995-05-02 JP JP7528991A patent/JPH10500946A/ja active Pending
- 1995-05-02 CA CA002187522A patent/CA2187522A1/en not_active Abandoned
- 1995-05-02 MX MX9605428A patent/MX9605428A/es unknown
- 1995-05-02 WO PCT/US1995/005026 patent/WO1995030684A1/en not_active Application Discontinuation
- 1995-05-02 HU HU9603110A patent/HUT75517A/hu unknown
-
1996
- 1996-11-08 KR KR1019960706331A patent/KR970702873A/ko not_active Application Discontinuation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2062641A (en) * | 1979-10-26 | 1981-05-28 | Roussel Uclaf | Anti inflammatory 17-chloroethynyl-11,17-dihydroxy androst-4-en-3-ones and derivatives thereof |
EP0153001A2 (en) * | 1984-02-03 | 1985-08-28 | The Upjohn Company | Steroids having an enamide or enimide group and their preparation |
WO1986000907A1 (en) * | 1984-07-23 | 1986-02-13 | Schering Aktiengesellschaft Berlin Und Bergkamen | Process for the manufacture of 6alpha-methyl steroids |
EP0181442A1 (de) * | 1984-09-17 | 1986-05-21 | Schering Aktiengesellschaft | Verfahren zur Herstellung von Pregnan-Derivaten |
DD281394A5 (de) * | 1984-12-10 | 1990-08-08 | Jenapharm Veb | Verfahren zur herstellung von steroid-c-17 alpha-carbonitrilen |
EP0263569A2 (en) * | 1986-10-10 | 1988-04-13 | Roussel-Uclaf | 9-alpha-hydroxysteroids, process for their preparation and process for the preparation of the corresponding 9(11)-dehydro-derivatives. |
EP0268400A1 (en) * | 1986-11-05 | 1988-05-25 | The Upjohn Company | Steroidal 17alpha-silyl ethers and process to corticoids and progesterones |
Also Published As
Publication number | Publication date |
---|---|
AU2362895A (en) | 1995-11-29 |
EP0759928A1 (en) | 1997-03-05 |
AU684946B2 (en) | 1998-01-08 |
HU9603110D0 (en) | 1997-01-28 |
CN1147816A (zh) | 1997-04-16 |
JPH10500946A (ja) | 1998-01-27 |
MX9605428A (es) | 1997-12-31 |
CA2187522A1 (en) | 1995-11-16 |
HUT75517A (en) | 1997-05-28 |
KR970702873A (ko) | 1997-06-10 |
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