NO135296B - - Google Patents
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- NO135296B NO135296B NO4152/72A NO415272A NO135296B NO 135296 B NO135296 B NO 135296B NO 4152/72 A NO4152/72 A NO 4152/72A NO 415272 A NO415272 A NO 415272A NO 135296 B NO135296 B NO 135296B
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- Prior art keywords
- methyl
- dione
- disemicarbazone
- compound
- acetate
- Prior art date
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 150000007659 semicarbazones Chemical group 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- -1 steroid compounds Chemical class 0.000 description 3
- UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- ASGJEMPQQVNTGO-UHFFFAOYSA-N benzene chloroform Chemical compound C(Cl)(Cl)Cl.C1=CC=CC=C1.C1=CC=CC=C1 ASGJEMPQQVNTGO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002036 chloroform fraction Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 150000003128 pregnanes Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- WSVOMANDJDYYEY-CWNVBEKCSA-N prednylidene Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](C(=C)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 WSVOMANDJDYYEY-CWNVBEKCSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- E—FIXED CONSTRUCTIONS
- E21—EARTH OR ROCK DRILLING; MINING
- E21B—EARTH OR ROCK DRILLING; OBTAINING OIL, GAS, WATER, SOLUBLE OR MELTABLE MATERIALS OR A SLURRY OF MINERALS FROM WELLS
- E21B47/00—Survey of boreholes or wells
- E21B47/12—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling
- E21B47/14—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling using acoustic waves
- E21B47/18—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling using acoustic waves through the well fluid, e.g. mud pressure pulse telemetry
-
- E—FIXED CONSTRUCTIONS
- E21—EARTH OR ROCK DRILLING; MINING
- E21B—EARTH OR ROCK DRILLING; OBTAINING OIL, GAS, WATER, SOLUBLE OR MELTABLE MATERIALS OR A SLURRY OF MINERALS FROM WELLS
- E21B47/00—Survey of boreholes or wells
- E21B47/12—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling
- E21B47/14—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling using acoustic waves
- E21B47/18—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling using acoustic waves through the well fluid, e.g. mud pressure pulse telemetry
- E21B47/20—Means for transmitting measuring-signals or control signals from the well to the surface, or from the surface to the well, e.g. for logging while drilling using acoustic waves through the well fluid, e.g. mud pressure pulse telemetry by modulation of mud waves, e.g. by continuous modulation
Landscapes
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Mining & Mineral Resources (AREA)
- Geology (AREA)
- Geophysics (AREA)
- Environmental & Geological Engineering (AREA)
- Fluid Mechanics (AREA)
- Remote Sensing (AREA)
- Acoustics & Sound (AREA)
- General Life Sciences & Earth Sciences (AREA)
- Geochemistry & Mineralogy (AREA)
- Earth Drilling (AREA)
- Arrangements For Transmission Of Measured Signals (AREA)
- Geophysics And Detection Of Objects (AREA)
- Steroid Compounds (AREA)
Description
Fremgangsmåte til fremstilling av nye 16-methylen- Process for the production of new 16-methylene-
11-oxygenerte steroider av pregnanrekken. 11-oxygenated steroids of the pregnane series.
Foreliggende oppfinnelse angår en fremgangsmåte til fremstilling av nye 16-methylen-ll-oxygenerte steroider av pregnanrekken og som er umettede i ring A. The present invention relates to a process for the production of new 16-methylene-11-oxygenated steroids of the pregnane series and which are unsaturated in ring A.
De forbindelser som fåes ved fremgangsmåten ifolge oppfinnelsen tilsvarer folgende generelle formel: The compounds obtained by the method according to the invention correspond to the following general formula:
i hvilken den strekede linje mellom carbonatomene i 1- og 2-stillingen betyr at der her kan være en enkelbinding eller dobbelbinding, mens R" betegner en hydroxylgruppe eller oxygen og X betegner hydrogen eller fluor. in which the dashed line between the carbon atoms in the 1- and 2-position means that there may be a single bond or a double bond, while R" denotes a hydroxyl group or oxygen and X denotes hydrogen or fluorine.
De,16-methylensteroider som fremstilles ved fremgangsmåten ifolge oppfinnelsen har en ytterst sterk anti-inflammatorisk virkning, betydelig storre enn utgangsmaterialenes virkning, og er særlig effektive til behandling av arthrit og lignende sykdommer, idet de gir cortisonlignende virkning allerede i små doser hvorved uonskede bivirkninger blir minimale. The ,16-methylene steroids that are produced by the method according to the invention have an extremely strong anti-inflammatory effect, significantly greater than the effect of the starting materials, and are particularly effective for the treatment of arthritis and similar diseases, as they give a cortisone-like effect already in small doses, thereby causing unwanted side effects becomes minimal.
Ifolge foreliggende oppfinnelse fremstilles steroidforbindelser med den ovenfor angitte generelle formel derved at en forbindelse med den ' generelle formel: According to the present invention, steroid compounds with the general formula stated above are produced by the fact that a compound with the general formula:
i hvilken X og R" har de ovenfor angitte betydninger, mens R betegner en methylgruppe i a- eller (3-konfigurasjonen, i flytende fase behandles med semicarbazid hvorved der dannes et 3,20-disemicarbazon, som omsettes med eddiksyre og eddiksyreanhydrid hvorved der dannes et 3,20-disemicarbazon-l,4,16-pregnatrien, hvilken forbindelse omsettes med vandig eddiksyre for fjernelse av semicarbazongruppene, hvorpå den således erholdte forbindelse behandles med hydrogenperoxyd hvorved der dannes den tilsvarende 16a, 17a-oxidoforbindelse, s--m behandles med en sterk syre, som hydrogenbromid, hydrogenklorid, hydrogen- in which X and R" have the meanings given above, while R denotes a methyl group in the a- or (3-configuration, in the liquid phase is treated with semicarbazide whereby a 3,20-disemicarbazone is formed, which is reacted with acetic acid and acetic anhydride whereby a 3,20-disemicarbazone-1,4,16-pregnatriene is formed, which compound is reacted with aqueous acetic acid to remove the semicarbazone groups, after which the compound thus obtained is treated with hydrogen peroxide whereby the corresponding 16a, 17a-oxido compound, s--m treated with a strong acid, such as hydrogen bromide, hydrogen chloride, hydrogen
fluorid eller perklorsyre, hvorved 17a-hydroxy-16-methylenforbindel-sen dannes. fluoride or perchloric acid, whereby the 17α-hydroxy-16-methylene compound is formed.
En fordel ved denne fremgangsmåte er at innforingen av 16-methylengruppen utgjor det siste trinn i syntesen av produktet. Methylengruppen er på grunn av tilstedeværelsen av dobbeltbindingen mere tilboyelig til å reagere enn en 16-methylgruppe. Av denne grunn kan ikke visse fremgangsmåter som er anvendbare ved fremstilling av 16-methylforbindelser, anvendes ved fremstilling av tilsvarende 16-methylenforbindelser. Ifolge foreliggende oppfinnelse loses dette problem ved at 16-methylengruppen fores inn i syntesens siste trinn. An advantage of this method is that the introduction of the 16-methylene group constitutes the last step in the synthesis of the product. The methylene group is, due to the presence of the double bond, more likely to react than a 16-methyl group. For this reason, certain methods which are applicable for the production of 16-methyl compounds cannot be used for the production of corresponding 16-methylene compounds. According to the present invention, this problem is solved by introducing the 16-methylene group into the last step of the synthesis.
Ifolge oppfinnelsen behandles en forbindelse med den generelle formel: i hvilken X, R" og R har de ovenfor angitte betydninger, med semicar-bazidbase eller semicarbazidhydroklorid for dannelse av det tilsvarende 3,20-semicarbazon med den generelle formel: According to the invention, a compound of the general formula: in which X, R" and R have the meanings given above, is treated with semicarbazide base or semicarbazide hydrochloride to form the corresponding 3,20-semicarbazone of the general formula:
Dette 3,20-semicarbazon overfores ved oppvarmning i eddiksyre og eddiksyreanhydrid til det tilsvarende, i 16-stillingen umettede 3,20-disemicarbazon, med den generelle formel: This 3,20-semicarbazone is transferred by heating in acetic acid and acetic anhydride to the corresponding 3,20-disemicarbazone unsaturated in the 16-position, with the general formula:
Dette i 16-stillingen umettede setnicarbazon overfores, f.eks. ved behandling med varm, vandig eddiksyre, til det tilsvarende 3,20-dion med den generelle formel: This in the 16-position unsaturated setnicarbazone is transferred, e.g. on treatment with hot, aqueous acetic acid, to the corresponding 3,20-dione with the general formula:
Denne forbindelse kan ved behandling med alkalisk hydrogenperoxyd i nærvær av en base eller med en organisk persyre overfores til det tilsvarende 16a,17a-oxyd med den generelle formel: This compound can, by treatment with alkaline hydrogen peroxide in the presence of a base or with an organic peracid, be converted to the corresponding 16a,17a-oxide with the general formula:
Dette 16a,17a-oxyd overfores ved behandling med en sterk syre, som en mineralsyre, f.eks. hydrogenbromid, hydrogenklorid, hydrogenfluorid eller perklorsyre, til det tilsvarende 16-methylenstero-id med den generelle formel: This 16a,17a-oxide is transferred by treatment with a strong acid, such as a mineral acid, e.g. hydrogen bromide, hydrogen chloride, hydrogen fluoride or perchloric acid, to the corresponding 16-methylene steroid with the general formula:
Fremgangsmåten ifolge oppfinnelsen er spesielt anvendbar til fremstilling av 9a-fluor-lip,17a,21-trihydroxy-16-methylen-1,4-pregnadien-3, 20-dion, 9a-fluor-lip,17a, 21-trihydroxy-16-methylen-4-pregnen-3,20-dion og 16-methylen-prednisolon fra deres 16a-methyl-eller 16(3-methylanaloger. The method according to the invention is particularly applicable to the production of 9a-fluoro-lip,17a,21-trihydroxy-16-methylene-1,4-pregnadiene-3,20-dione, 9a-fluoro-lip,17a,21-trihydroxy-16 -methylene-4-pregnene-3,20-dione and 16-methylene-prednisolone from their 16α-methyl-or 16(3-methyl analogues.
16-methylensteroidene har som foran nevnt en meget sterk inflammasjonshemmende virkning og kan administreres oralt, parenter-alt eller topisk. Forbindelsene kan herved anvendes alene eller sam-men med bærere eller fortynningsmidler. For oppnåelsen av samme tera-peutiske effekt kreves der mindre mengder av forbindelsene fremstil-let ifolge oppfinnelsen enn av andre steroidforbindelser som cortison og hydrocortison. As mentioned above, the 16-methylene steroids have a very strong anti-inflammatory effect and can be administered orally, parenterally or topically. The compounds can thereby be used alone or together with carriers or diluents. For the achievement of the same therapeutic effect, smaller quantities of the compounds produced according to the invention are required than of other steroid compounds such as cortisone and hydrocortisone.
I det folgende beskrives som eksempler noen utforelsesfor-mer for fremgangsmåten ifolge oppfinnelsen. In the following, some embodiments of the method according to the invention are described as examples.
Eksempel 1 Fremstilling av 3,20-disemicarbazonet av 9a-fluor- . Example 1 Preparation of the 3,20-disemicarbazone from 9a-fluoro-.
lip, 17a, 21-trihydroxy-16a-methyl-l,4-pregnadien-3,20-dion lip, 17a, 21-trihydroxy-16a-methyl-1,4-pregnadiene-3,20-dione
En blanding av 1,00 g 9a-fluor-lip,17a,21-trihydroxy-16a-methyl-1,4-pregnadien-3,20-dion, 750 mg semicarbazid-base, 280 mg semicarbazidhydroklorid i 20 ml methanol og 10 ml dimethylformamid oppvarmes i 20 timer under tilbakelSpskjoling i nitrogenatmosfære. Blandingen avkjoles derpå til 20°C og ti-lsettes lOO ml vann under omroring. Det herved utfeldte 3, 20-disemicarbazon av 9a-f luor-HB, 17a, 21-trihydroxy-16a-methyl-l,4-pregnadien-3,20-dion frafiltreres, vaskes med vann og tdrres i luften. Produktets smeltepunkt er over 300°C. A mixture of 1.00 g of 9α-fluoro-lip,17α,21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione, 750 mg of semicarbazide base, 280 mg of semicarbazide hydrochloride in 20 ml of methanol and 10 ml of dimethylformamide is heated for 20 hours under reflux in a nitrogen atmosphere. The mixture is then cooled to 20°C and 100 ml of water is added while stirring. The thereby precipitated 3, 20-disemicarbazone of 9a-fluoro-HB, 17a, 21-trihydroxy-16a-methyl-1,4-pregnadiene-3,20-dione is filtered off, washed with water and dried in the air. The product's melting point is over 300°C.
y\ CH OH 2Q2 mfji Em 25 5QQ. 240 mu. Em 21,400. y\ CH OH 2Q2 mfji Em 25 5QQ. 240 mu. Em 21,400.
ms les ms read
På lignende måte kan man fremstille 3,20-disemicarbazonet av 9a-fluor-llB,17a,21-trihydroxy-16p-methyl-l,4-pregnadien-3,20-dion, 3,20-disemicarbazonet av lip,17a,21-trihydroxy-16a-methyl-l,4-pregna-dien-3,20-dion, 3,20-disemicarbazonet av lip,17a,21-trihydroxy-16p-methyl-1,4-pregnadien-3,20-dion, 3,20-disemicarbazonet av 17a,21-dihydroxy-16a-methyl-l,4-pregnadien-3,11,20-trion, 3,20-disemicarbazonet av 17a,21-dihydroxy-16S-methyl-l,4-pregnadien-3,11,20-trion, 3, 20-disemicarbazonet av 9a-fluor-lip, 17a, 21-trihydroxy-16a-methyl-4-pregnen-3,20-dion, 3,20-disemicarbazonet av 9a-fluor-lip,17a,21-trihydroxy-16B-methyl-4-pregnen-3,20-dion, 3,20-disemicarbazonet av lip,17a,21-trihydroxy-16a-methyl-4-pregnen-3,20-dion, 3,20-disemicarbazonet av lip,17a> 21-trihydroxy-16p-methyl-4-pregnen-3,20-dion, 3,20-disemicarbazonet av 17a,21-dihydroxy-16a-methyl-4-pregnen-3,11, 20-trion og 3,20-disemicarbazonet av 17a,21-dihydroxy-16p-methyl-4-pregnen-3,11,20-trion. In a similar way, one can prepare the 3,20-disemicarbazone of 9a-fluoro-11B,17a,21-trihydroxy-16p-methyl-1,4-pregnadiene-3,20-dione, the 3,20-disemicarbazone of lip,17a, 21-trihydroxy-16α-methyl-1,4-pregna-diene-3,20-dione, the 3,20-disemicarbazone of lip,17α,21-trihydroxy-16β-methyl-1,4-pregnadiene-3,20- dione, the 3,20-disemicarbazone of 17a,21-dihydroxy-16a-methyl-1,4-pregnadiene-3,11,20-trione, the 3,20-disemicarbazone of 17a,21-dihydroxy-16S-methyl-l, 4-pregnadiene-3,11,20-trione, 3, 20-disemicarbazone of 9a-fluoro-lip, 17a, 21-trihydroxy-16a-methyl-4-pregnene-3,20-dione, 3,20-disemicarbazone of 9a-fluoro-lip,17a,21-trihydroxy-16B-methyl-4-pregnen-3,20-dione, the 3,20-disemicarbazone of lip,17a,21-trihydroxy-16a-methyl-4-pregnen-3, 20-dione, 3,20-disemicarbazone of lip,17a> 21-trihydroxy-16p-methyl-4-pregnen-3,20-dione, 3,20-disemicarbazone of 17a,21-dihydroxy-16a-methyl-4- pregnene-3,11,20-trione and the 3,20-disemicarbazone of 17α,21-dihydroxy-16β-methyl-4-pregnene-3,11,20-trione.
Eksempel 2 Fremstilling av 9a-fluor-lip,21-dihydroxy-16-methyl-1, 4, 16- pregnatrien- 3, 20- dion- 21- acetat Example 2 Preparation of 9a-fluoro-lip,21-dihydroxy-16-methyl-1,4,16-pregnatriene-3,20-dione-21-acetate
En oppløsning av 500 mg av 3,20-disemicarbazonet av 9a-f luor-lip, 17a-, 21-1rihydroxy-16a-methyl-1, 4-pregnadien-3, 20-dion i 10 ml eddiksyre og 0,5 ml eddiksyreanhydrid oppvarmes i nitrogenatmosfæ- A solution of 500 mg of the 3,20-disemicarbazone of 9α-fluorolip, 17α-, 21-1rihydroxy-16α-methyl-1, 4-pregnadiene-3, 20-dione in 10 ml of acetic acid and 0.5 ml acetic anhydride is heated in a nitrogen atmosphere
i in
re under tilbakelopskjoling i 1 time, hvorved der dannes det tilsvarende 3,20-disemicarbazon av lip,21-dihydroxy-16-methyl-l,4,16-pregna-trien-3,20-dion-21-acetat. Derefter avkjoles reaksjonsblandingen, tilsettes 13 ml vann og oppvarmes på dampbad i 5 timer. Den inndampes så i vakuum hesten til torrhet og tilsettes vann samt kloroform. Blandingen ekstraheres derefter grundig med kloroform. Kloroformekstraktet vaskes med et overskudd av vandig kaliumbikarbonatopplosning og med mettet koksaltopplosning, hvorpå det befries for vann med mag-nesiumsu.lf at. Opplosningen inndampes til torrhet, og residuet kromatograferes i noytralt aluminiumoxyd med påfolgende krystallisasjon av benzen-kloroformfraksjonene, hvorved man får 9a-fludr-lip,21-dihydroxy-16-methyl-l,4,16-pregnatrien-3,20-dion-21-acetat, sm.p. 228-233°C. under reflux for 1 hour, whereby the corresponding 3,20-disemicarbazone of lip,21-dihydroxy-16-methyl-1,4,16-pregna-triene-3,20-dione-21-acetate is formed. The reaction mixture is then cooled, 13 ml of water is added and heated on a steam bath for 5 hours. It is then evaporated in a vacuum to dryness and water and chloroform are added. The mixture is then thoroughly extracted with chloroform. The chloroform extract is washed with an excess of aqueous potassium bicarbonate solution and with saturated sodium chloride solution, after which it is freed from water with magnesium sulfate. The solution is evaporated to dryness, and the residue is chromatographed in neutral aluminum oxide with subsequent crystallization of the benzene-chloroform fractions, whereby 9a-fludr-lip,21-dihydroxy-16-methyl-1,4,16-pregnatriene-3,20-dione is obtained 21-acetate, m.p. 228-233°C.
l MeOH l MeOH
maks 243 myL iEm 22'00°- max 243 myL iEm 22'00°-
Ved lignende behandling av 3,20-disemicarbazonet av 9a-fluor-lip,17a,21-trihydroxy-16p-methyl-l,4-pregnadien-3,20-dion får man likeledes 9a-fluor-lip,21-dihydroxy-16-methyl-l,4,16-pregnatrien-3,20-dion-21-acetat. By similar treatment of the 3,20-disemicarbazone of 9a-fluoro-lip,17a,21-trihydroxy-16p-methyl-1,4-pregnadiene-3,20-dione, 9a-fluoro-lip,21-dihydroxy- 16-methyl-1,4,16-pregnatriene-3,20-dione-21-acetate.
På lignende måte får man lip,21-dihydroxy-16-methyl-l,4,16-pregnatrien-3,20-dion-21-acetat, 21-hydroxy-16-methyl-l,4,16-pregna-trien-3,11,20-trion-21,acetat, 9a-fluor-lip,21-dihydroxy-16-methyl-4,16-pregnadien-3,20-dion-21-acetat, lip,21-dihydroxy-16-methyl-4,16-pregnadien-3,20-dion-21-acetat og 21-hydroxy-16-methyl-4,16-pregnadi-en-3,ll,20-trion-21-acetat. In a similar way one obtains lip,21-dihydroxy-16-methyl-1,4,16-pregnatriene-3,20-dione-21-acetate, 21-hydroxy-16-methyl-1,4,16-pregna-triene -3,11,20-trione-21,acetate, 9a-fluoro-lip,21-dihydroxy-16-methyl-4,16-pregnadiene-3,20-dione-21-acetate, lip,21-dihydroxy-16 -methyl-4,16-pregnadiene-3,20-dione-21-acetate and 21-hydroxy-16-methyl-4,16-pregnadiene-3,11,20-trione-21-acetate.
Eksempel 3 Fremstilling av 9a-fluor-lip,21-dihydroxy-16p-methyl-16a, 17a- oxido- l, 4- pregnadien- 3, 20- dion- 21- acetat Example 3 Preparation of 9a-fluoro-lip,21-dihydroxy-16p-methyl-16a,17a-oxidol-1,4-pregnadiene-3,20-dione-21-acetate
En opplosning av 500 mg 9a-fluor-llB,21-dihydroxy-16-methyl-1,4,16-pregnatrien-3,20-dion-21-acetat i 5 ml benzen og 5 ml kloroform tilsettes under omroring 0,50 ml t-butylhydroperoxyd og 0,1 ml av en 35 %'s opplosning av benzyltrimethyl-ammoniumhydroxyd i methanol. Efter 18 timers henstand ved romtemperatur tilsettes blandingen vann og den ekstraheres grundig med kloroform. Kloroformekstraktet vaskes med mettet vandig natriumkloridopplosning og befries for vann med magnesiumsulfat. Ved fordampning av opplosningsmid-let og krystallisasjon av residuet fra en blanding av aceton og ether får man 9a-fluor-lip,21-dihydroxy-16S-methyl-16a,17a-oxido-1,4-preg-nadien-3,20-dion-21-acetat. A solution of 500 mg of 9a-fluoro-11B,21-dihydroxy-16-methyl-1,4,16-pregnatriene-3,20-dione-21-acetate in 5 ml of benzene and 5 ml of chloroform is added while stirring 0.50 ml of t-butyl hydroperoxide and 0.1 ml of a 35% solution of benzyltrimethylammonium hydroxide in methanol. After standing for 18 hours at room temperature, water is added to the mixture and it is extracted thoroughly with chloroform. The chloroform extract is washed with saturated aqueous sodium chloride solution and freed from water with magnesium sulfate. Evaporation of the solvent and crystallization of the residue from a mixture of acetone and ether gives 9a-fluoro-lip,21-dihydroxy-16S-methyl-16a,17a-oxido-1,4-pregnadiene-3,20 -dione-21-acetate.
På lignende måte kan man fremstille 11B,21-dihydroxy-16B-methyl-16a,17a-oxido-l,4-pregnadien-3,20-dion-21-acetat, 21-hydroxy-166-methyl-16a,17a-oxido-l,4-pregnadien-3,11,20-trion-21,acetat, 9a-fluor-11B,21-dihydroxy-16p-methyl-16a,17a-oxido-4-pregnen-3,20-dion-21-acetat, lip, 21-dihydroxy- 16B-methyl- 16a, 17a-oxido-4-pregnen-3, 20-dion-21-acetat og 21-hydroxy-16B-methyl-16a,17a-oxido-4-pregnen,3,11, 20-trion-21-acetat. In a similar way, one can prepare 11B,21-dihydroxy-16B-methyl-16a,17a-oxido-1,4-pregnadiene-3,20-dione-21-acetate, 21-hydroxy-166-methyl-16a,17a- oxido-1,4-pregnadiene-3,11,20-trione-21,acetate, 9a-fluoro-11B,21-dihydroxy-16p-methyl-16a,17a-oxido-4-pregnene-3,20-dione- 21-acetate, lip, 21-dihydroxy- 16B-methyl- 16a, 17a-oxido-4-pregnen-3, 20-dione-21-acetate and 21-hydroxy-16B-methyl-16a,17a-oxido-4- pregnene,3,11,20-trione-21-acetate.
Eksempel 4 Fremstilling av 9a-fluor-llS,17a,21-trihydroxy-16-methylen- 1, 4- pregnadien- 3, 20- dion- 21- acetat Example 4 Preparation of 9a-fluoro-11S,17a,21-trihydroxy-16-methylene-1,4-pregnadiene-3,20-dione-21-acetate
En opplosning av 600 mg 9a-fluor-11B,21-dihydroxy-16S-methyl-16a,17a-oxido-l,4-pregnadien-3,20-dion-21-acetat i 10 ml eddiksyre og som holdes ved 10 - 15°C tilsettes under omroring 3 ml av en 10 %'s kold opplosning av hydrogenbromid i eddiksyre. Efter 30 minut-ters henstand inndampes blandingen til torrhet i vakuum ved en tempe-ratur på 15°C, og residuet kromatograferes i noytralt aluminiumoxyd. Ved kombinasjon av de passende benzen-kloroform-fraksjoner og krystallisasjon får man det onskede 9a-fluor-lip,17a,21-trihydroxy-16-methylen-1,4-pregnadien-3,20-dion-21-acetat. A solution of 600 mg of 9a-fluoro-11B,21-dihydroxy-16S-methyl-16a,17a-oxido-1,4-pregnadiene-3,20-dione-21-acetate in 10 ml of acetic acid and which is kept at 10 - 15°C, 3 ml of a 10% cold solution of hydrogen bromide in acetic acid are added while stirring. After a period of 30 minutes, the mixture is evaporated to dryness in vacuum at a temperature of 15°C, and the residue is chromatographed in neutral aluminum oxide. By combining the appropriate benzene-chloroform fractions and crystallization, the desired 9α-fluoro-lip,17α,21-trihydroxy-16-methylene-1,4-pregnadiene-3,20-dione-21-acetate is obtained.
På lignende måte kan man fremstille 11B,17a,21-trihydroxy-16-methylen-l,4-pregnadien-3,20-dion-21-acetat, 17a,21-dihydroxy-16-methylen-1, 4-pregnadien-3, ll,'20-trion-21-acetat, 9a-f luor-lip, 17a, 21-trihydroxy-16-methylen-4-pregnen-3,20-dion-21-acetat, lip,17a,21-tri-hydrozy-16-methylen-4-pregnen-3,20-dion-21-acetat og 17 a,21-dihydroxy-16-methylcn-4-pregnen-3,11,20-trion-21-acetat. In a similar way, one can prepare 11B,17a,21-trihydroxy-16-methylene-1,4-pregnadiene-3,20-dione-21-acetate, 17a,21-dihydroxy-16-methylene-1,4-pregnadiene- 3, 11,'20-trione-21-acetate, 9a-fluoro-lip, 17a, 21-trihydroxy-16-methylene-4-pregnene-3,20-dione-21-acetate, lip,17a,21- tri-hydrozy-16-methylene-4-pregnene-3,20-dione-21-acetate and 17 α,21-dihydroxy-16-methylcn-4-pregnene-3,11,20-trione-21-acetate.
Alternativt kan man til en opplosning av 500 mg 9a-fluor-11(3, 21-dihydroxy-16p-methyl-16a, 17a-oxido-1, 4-prognadien-3; 20--dion-21-acetat i 2,4 ml tetrahydrofuran under omroring tilsette 3,5 ml av en blanding av hydrogenfluorid og tetrahydrofuran i vektforholdet 2 : 1. Efter 2 timers henstand ved 15°C bringes reaksjonsblandingen langsomt med en pipette i et overskudd av kold, vandig natriumkarbo-natopplosning. Den erholdte blanding ekstraheres med kloroform,og kloroformekstraktet vaskes med vann samt med mettet, vandig natriumkloridopplosning. Den inndampes derpå til torrhet, og residuet kromatograferes i noytralt aluminiumoxyd, hvorved man får det onskede 9a-fluor-lip,17a,21-trihydroxy-16-methylen-l,4-pregnadien-3,20-dion-21-acetat. Alternatively, a solution of 500 mg of 9a-fluoro-11(3, 21-dihydroxy-16p-methyl-16a, 17a-oxido-1, 4-prognadiene-3; 20--dione-21-acetate in 2, 4 ml of tetrahydrofuran, while stirring, add 3.5 ml of a mixture of hydrogen fluoride and tetrahydrofuran in the weight ratio 2 : 1. After standing for 2 hours at 15°C, the reaction mixture is brought slowly with a pipette into an excess of cold, aqueous sodium carbonate solution. The obtained mixture is extracted with chloroform, and the chloroform extract is washed with water and with saturated, aqueous sodium chloride solution. -1,4-pregnadiene-3,20-dione-21-acetate.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21306171A | 1971-12-28 | 1971-12-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO135296B true NO135296B (en) | 1976-12-06 |
| NO135296C NO135296C (en) | 1977-03-16 |
Family
ID=22793597
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO4152/72A NO135296C (en) | 1971-12-28 | 1972-11-15 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US3789355A (en) |
| AU (1) | AU473372B2 (en) |
| CA (1) | CA968883A (en) |
| DK (1) | DK157213C (en) |
| GB (1) | GB1404620A (en) |
| IE (1) | IE37814B1 (en) |
| MY (1) | MY7600056A (en) |
| NL (1) | NL173875C (en) |
| NO (1) | NO135296C (en) |
| OA (1) | OA04307A (en) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3982224A (en) * | 1973-08-23 | 1976-09-21 | Mobil Oil Corporation | Method and apparatus for transmitting downhole information from a well |
| US3997867A (en) * | 1973-09-17 | 1976-12-14 | Schlumberger Technology Corporation | Well bore data-transmission apparatus |
| US4001775A (en) * | 1973-10-03 | 1977-01-04 | Mobil Oil Corporation | Automatic bit synchronization method and apparatus for a logging-while-drilling receiver |
| US3983948A (en) * | 1974-07-01 | 1976-10-05 | Texas Dynamatics, Inc. | Method and apparatus for indicating the orientation of a down hole drilling assembly |
| US4021773A (en) * | 1974-10-29 | 1977-05-03 | Sun Oil Company Of Pennsylvania | Acoustical pick-up for reception of signals from a drill pipe |
| US4078620A (en) * | 1975-03-10 | 1978-03-14 | Westlake John H | Method of and apparatus for telemetering information from a point in a well borehole to the earth's surface |
| US4147223A (en) * | 1976-03-29 | 1979-04-03 | Mobil Oil Corporation | Logging-while-drilling apparatus |
| US4167000A (en) * | 1976-09-29 | 1979-09-04 | Schlumberger Technology Corporation | Measuring-while drilling system and method having encoder with feedback compensation |
| US4103281A (en) * | 1976-09-29 | 1978-07-25 | Schlumberger Technology Corporation | Measuring-while-drilling system having motor speed detection during encoding |
| US4100528A (en) * | 1976-09-29 | 1978-07-11 | Schlumberger Technology Corporation | Measuring-while-drilling method and system having a digital motor control |
| US4215427A (en) * | 1978-02-27 | 1980-07-29 | Sangamo Weston, Inc. | Carrier tracking apparatus and method for a logging-while-drilling system |
| US4215425A (en) * | 1978-02-27 | 1980-07-29 | Sangamo Weston, Inc. | Apparatus and method for filtering signals in a logging-while-drilling system |
| US4216536A (en) * | 1978-10-10 | 1980-08-05 | Exploration Logging, Inc. | Transmitting well logging data |
| US4733233A (en) * | 1983-06-23 | 1988-03-22 | Teleco Oilfield Services Inc. | Method and apparatus for borehole fluid influx detection |
| US4733232A (en) * | 1983-06-23 | 1988-03-22 | Teleco Oilfield Services Inc. | Method and apparatus for borehole fluid influx detection |
| US5220963A (en) * | 1989-12-22 | 1993-06-22 | Patton Consulting, Inc. | System for controlled drilling of boreholes along planned profile |
| US5154078A (en) * | 1990-06-29 | 1992-10-13 | Anadrill, Inc. | Kick detection during drilling |
| US5275040A (en) * | 1990-06-29 | 1994-01-04 | Anadrill, Inc. | Method of and apparatus for detecting an influx into a well while drilling |
| US5375098A (en) * | 1992-08-21 | 1994-12-20 | Schlumberger Technology Corporation | Logging while drilling tools, systems, and methods capable of transmitting data at a plurality of different frequencies |
| US5237540A (en) * | 1992-08-21 | 1993-08-17 | Schlumberger Technology Corporation | Logging while drilling tools utilizing magnetic positioner assisted phase shifts |
| US5249161A (en) * | 1992-08-21 | 1993-09-28 | Schlumberger Technology Corporation | Methods and apparatus for preventing jamming of encoder of logging while drilling tool |
| US5293937A (en) * | 1992-11-13 | 1994-03-15 | Halliburton Company | Acoustic system and method for performing operations in a well |
| NO305219B1 (en) * | 1994-03-16 | 1999-04-19 | Aker Eng As | Method and transmitter / receiver for transmitting signals via a medium in tubes or hoses |
| US5490121A (en) * | 1994-08-17 | 1996-02-06 | Halliburton Company | Nonlinear equalizer for measurement while drilling telemetry system |
| US5668457A (en) * | 1995-06-30 | 1997-09-16 | Martin Marietta Corporation | Variable-frequency AC induction motor controller |
| GB9607297D0 (en) * | 1996-04-09 | 1996-06-12 | Anadrill Int Sa | Noise detection and suppression system for wellbore telemetry |
| US5864772A (en) * | 1996-12-23 | 1999-01-26 | Schlumberger Technology Corporation | Apparatus, system and method to transmit and display acquired well data in near real time at a remote location |
| US6360823B1 (en) * | 2000-07-20 | 2002-03-26 | Intevep, S.A. | Apparatus and method for performing downhole measurements |
| GB2405725B (en) * | 2003-09-05 | 2006-11-01 | Schlumberger Holdings | Borehole telemetry system |
| US6998724B2 (en) * | 2004-02-18 | 2006-02-14 | Fmc Technologies, Inc. | Power generation system |
| US7348893B2 (en) * | 2004-12-22 | 2008-03-25 | Schlumberger Technology Corporation | Borehole communication and measurement system |
| WO2007076039A2 (en) * | 2005-12-20 | 2007-07-05 | Massachusetts Institute Of Technology | Communications and power harvesting system for in-pipe wireless sensor networks |
| US20090038804A1 (en) * | 2007-08-09 | 2009-02-12 | Going Iii Walter S | Subsurface Safety Valve for Electric Subsea Tree |
| US8151905B2 (en) * | 2008-05-19 | 2012-04-10 | Hs International, L.L.C. | Downhole telemetry system and method |
| WO2010024872A1 (en) * | 2008-08-23 | 2010-03-04 | Herman Collette | Method of communication using improved multi frequency hydraulic oscillator |
| US8302685B2 (en) * | 2009-01-30 | 2012-11-06 | Schlumberger Technology Corporation | Mud pulse telemetry data modulation technique |
| BE1019411A4 (en) | 2010-07-09 | 2012-07-03 | Ion Beam Applic Sa | MEANS FOR MODIFYING THE MAGNETIC FIELD PROFILE IN A CYCLOTRON. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2700131A (en) * | 1951-07-20 | 1955-01-18 | Lane Wells Co | Measurement system |
| US3015801A (en) * | 1959-06-16 | 1962-01-02 | David C Kalbfell | Drill pipe module data collection and transmission system |
| US3309656A (en) * | 1964-06-10 | 1967-03-14 | Mobil Oil Corp | Logging-while-drilling system |
| US3622971A (en) * | 1969-06-30 | 1971-11-23 | Arps Corp | Method and apparatus for surveying the direction and inclination of a borehole |
-
1971
- 1971-12-28 US US00213061A patent/US3789355A/en not_active Expired - Lifetime
-
1972
- 1972-11-15 NO NO4152/72A patent/NO135296C/no unknown
- 1972-11-23 AU AU49183/72A patent/AU473372B2/en not_active Expired
- 1972-11-27 IE IE1647/72A patent/IE37814B1/en unknown
- 1972-11-29 GB GB5513472A patent/GB1404620A/en not_active Expired
- 1972-12-19 CA CA159,440A patent/CA968883A/en not_active Expired
- 1972-12-26 OA OA54798A patent/OA04307A/en unknown
- 1972-12-27 DK DK647472A patent/DK157213C/en not_active IP Right Cessation
- 1972-12-28 NL NLAANVRAGE7217775,A patent/NL173875C/en not_active IP Right Cessation
-
1976
- 1976-12-30 MY MY56/76A patent/MY7600056A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA968883A (en) | 1975-06-03 |
| NL7217775A (en) | 1973-07-02 |
| US3789355A (en) | 1974-01-29 |
| IE37814B1 (en) | 1977-10-26 |
| OA04307A (en) | 1980-01-15 |
| AU4918372A (en) | 1974-05-23 |
| AU473372B2 (en) | 1976-06-17 |
| DK157213C (en) | 1990-04-23 |
| IE37814L (en) | 1973-06-28 |
| GB1404620A (en) | 1975-09-03 |
| DK157213B (en) | 1989-11-20 |
| NL173875C (en) | 1984-03-16 |
| NO135296C (en) | 1977-03-16 |
| MY7600056A (en) | 1976-12-31 |
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