DE1224739B - Process for the preparation of 16beta-lower-alkylthio-2, 5 (10) -oestradien-3, 17beta-diol-3-lower alkylthio-ethers - Google Patents
Process for the preparation of 16beta-lower-alkylthio-2, 5 (10) -oestradien-3, 17beta-diol-3-lower alkylthio-ethersInfo
- Publication number
- DE1224739B DE1224739B DES84031A DES0084031A DE1224739B DE 1224739 B DE1224739 B DE 1224739B DE S84031 A DES84031 A DE S84031A DE S0084031 A DES0084031 A DE S0084031A DE 1224739 B DE1224739 B DE 1224739B
- Authority
- DE
- Germany
- Prior art keywords
- alkylthio
- diol
- ether
- ethers
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 3
- 125000005012 alkyl thioether group Chemical group 0.000 title 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 150000005215 alkyl ethers Chemical class 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 229960003604 testosterone Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- ULAADVBNYHGIBP-GFEQUFNTSA-N (8r,9s,13s,14s,17s)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-ol Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 ULAADVBNYHGIBP-GFEQUFNTSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 206010054834 Hypergonadism Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000002054 antogonadotrophic effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- -1 lithium aluminum hydride Chemical compound 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SQMCFUSVGSBKFK-UHFFFAOYSA-M sodium;5-(cyclohexen-1-yl)-1,5-dimethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].O=C1N(C)C(=O)[N-]C(=O)C1(C)C1=CCCCC1 SQMCFUSVGSBKFK-UHFFFAOYSA-M 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY
ΐΓϋΊΐΐΓϋΊΐ
Int. CL:Int. CL:
C07cC07c
AUSLEGESCHRIFTEDITORIAL
Nummer:
Aktenzeichen:
Anmeldetag:
Auslegetag:Number:
File number:
Registration date:
Display day:
Deutsche KL: 12 ο-25/07 German KL: 12 ο -25/07
1224739 S84031IVb/12o 6. März 1963 15. September 19661224739 S84031IVb / 12o March 6, 1963 September 15, 1966
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von 2,5(10)-östradien-3,17-diol-3-niederalkyläthern der allgemeinen Formel I Verfahren zur Herstellung von 16/?-Niederalkylthio-2,5(10)-östradien-3,17y3-diol- 3-niederalkyläthernThe present invention relates to a process for the preparation of 2,5 (10) -estradiene-3,17-diol-3-lower alkyl ethers of the general formula I process for the preparation of 16 /? - lower alkylthio-2,5 (10) -estradiene-3,17y3-diol- 3-lower alkyl ethers
RO-1 RO- 1
SR'SR '
(I)(I)
worin R und R' je eine niedere Alkylgruppe, z. B. die Methyl-, Äthyl-, Propyl- oder Butylgruppe, bedeuten. wherein R and R 'each represent a lower alkyl group, e.g. B. the methyl, ethyl, propyl or butyl group mean.
Die Verfahrensprodukte (I) besitzen eine erhebliche inhibierende Wirkung auf die Gonadotropin-Sekretion, wie sie sich bei der Behandlung von Hypergonadismen oder ähnlichen durch Hypersekretion von Sexualhormonen, z. B. Androgenen oder östrogenen, verursachten Krankheiten zeigt, da sie sehr geringe hormonale Wirksamkeiten aufweisen wie andere antigonadotropisch wirksame Stoffe, z. B. Testosteron oder östron.The process products (I) have a significant inhibiting effect on gonadotropin secretion, as it is in the treatment of hypergonadisms or the like due to hypersecretion of sex hormones, e.g. B. androgens or estrogenic diseases caused shows there they have very low hormonal activities like other antigonadotropic substances, e.g. B. Testosterone or estrone.
Das erfindungsgemäße Verfahren-ist nun dadurch gekennzeichnet, daß man in an sich bekannter Weise einen 16(5-Niederalkylthio-l,3,5(10)-östratrien-3,17-diol-3-niederalkyläther der allgemeinen Formel IIThe process according to the invention is now characterized in that it is carried out in a manner known per se a 16 (5-lower alkylthio-1,3,5 (10) -estratriene-3,17-diol-3-lower alkyl ether of the general formula II
SR'SR '
(Π) Anmelder:(Π) Applicant:
Shionogi & Co., Ltd., Osaka (Japan)Shionogi & Co., Ltd., Osaka (Japan)
Vertreter:Representative:
Dr. phil. Dr. rer. pol. K. Köhler, Patentanwalt, München 2, Amalienstr. 15Dr. phil. Dr. rer. pole. K. Köhler, patent attorney, Munich 2, Amalienstr. 15th
Als Erfinder benannt:Named as inventor:
Norio Tokutake, Kobe-shi (Japan)Norio Tokutake, Kobe-shi (Japan)
Beanspruchte Priorität:Claimed priority:
Japan vom 10. März 1962 (9500)Japan March 10, 1962 (9500)
nach folgendem Schema herstellen:manufacture according to the following scheme:
worin R und R' die oben angegebene Bedeutung haben, mit einem Alkalimetall, wie z. B. Lithium, Natrium oder Kalium, in Gegenwart eines niederen Alkanols, wie beispielsweise Methanol oder Äthanol, in flüssigem Ammoniak, vorzugsweise bei tiefen Temperaturen, beispielsweise unter Kühlung mit einer Trockeneis-Aceton-Mischung, reduziert.wherein R and R 'have the meaning given above, with an alkali metal, such as. B. Lithium, Sodium or potassium, in the presence of a lower alkanol such as methanol or ethanol, in liquid ammonia, preferably at low temperatures, for example with cooling a dry ice-acetone mixture.
Die verfahrensgemäß, einzusetzenden Ausgangsstoffe kann man aus den bekannten 16a-Bromöstron-3-niederalkyl-äthern (Johnson und Mitarbeiter, J. Am. Chem. Soc, 79 [1957], S. 2005) Kalium-The starting materials to be used according to the process can be obtained from the known 16a-bromoestrone-3-lower alkyl ethers (Johnson and coworkers, J. Am. Chem. Soc, 79 [1957], p. 2005) potassium
niederalkylmercaptid >
in Aceton lower alkyl mercaptide >
in acetone
RORO
Reduktion
mit Lithiumaluminiumhydrid reduction
with lithium aluminum hydride
SR'SR '
OHOH
SR'SR '
Für die Herstellung dieser Ausgangsstoffe wird im Rahmen der vorliegenden Erfindung Schutz nicht begehrt.For the production of these starting materials, protection is not given in the context of the present invention desired.
Die so erhaltenen 16(S-Niederalkylthio-l,4-dihydro-3,17/?-östradiol-3-niederalkyläther (I) besitzen eineThe 16 (S-lower alkylthio-1,4-dihydro-3,17 /? - estradiol-3-lower alkyl ether (I) own a
609 660/431609 660/431
bemerkenswerte hypophysäre gonadotrophininhibierende Wirksamkeit. Zum Beispiel führt der 16ß-Äthylthio-l,4-dihydro-3,17^-östradiol-3-methyläther zu einer größeren Hemmung der genannten Schleimabsonderung als das bekannte Testosteron, wie dies aus der folgenden Tabelle zu ersehen ist.notable pituitary gonadotrophin inhibitors Effectiveness. For example, the 16β-ethylthio-1,4-dihydro-3,17 ^ -estradiol-3-methyl ether to a greater inhibition of said mucus secretion than the well-known testosterone, like this from can be seen in the following table.
dosistotal
dose
EierstocksWeight of
Ovary
mungHem
mung
hydro-3,17/S-östradiol-
3-methyläther16j8-ethylthio-1,4-di-
hydro-3.17 / S-estradiol-
3-methyl ether
Männchen — WeibchenUntouched
Males - females
Männchen —WeibchenCastrated
Males - females
IOIO
Parabiose unter anästhetischen Bedingungen mit Natriummethylhexabital vereinigt. Die Einschnittwunden wurden mit Metallklammern vereinigt, und es wurde Penicillin mit einer Dosis von 1500 I. E. pro Teilnehmer injiziert. Am Tage der parabiotischen Operation wurde mit subkutanen Injektionen an kastrierten männlichen Mäusen einmal täglich während 10 Tagen mit einer geeigneten Dosis der testierten Verbindung begonnen, welche Verbindung in 0,1 ml eines Vehikels, bestehend aus 0,9% Natriumchlorid, 0,4% Polysorbat 80, 0,5% Carboxymethylcellulose und 0,9% Benzylalkohol, in Wasser suspendiert war. Am 11. Tag wurden die Tiere einer Autopsie unterworfen, und es wurde das Gewicht der Eierstöcke bestimmt. Die Prozente der Hemmung des Eierstockwachstums wurde gemäß der folgenden Formel berechnet:Parabiosis combined with sodium methylhexabital under anesthetic conditions. The incision wounds were combined with metal clips and penicillin was administered at a dose of 1500 I.U. injected per participant. On the day of the parabiotic operation, subcutaneous injections were started castrated male mice once a day for 10 days with an appropriate dose of that tested Compound started, which compound in 0.1 ml of a vehicle consisting of 0.9% sodium chloride, 0.4% polysorbate 80, 0.5% carboxymethyl cellulose and 0.9% benzyl alcohol was suspended in water. On the 11th day, the animals were autopsied and it was the ovarian weight certainly. The percent inhibition of ovarian growth was determined according to the following formula calculated:
(F-C)(F-C)
100100
(V-Vi)(V-Vi)
2020th
Prüfverfahren: Kastrierte männliche Mäuse wurden jede mit unberührten weiblichen Mäusen in worin V, C und Vi die durchschnittlichen Eierstockgewichte der intakten Partner verbunden mit dem vehikelinjizierten kastrierten Männchen, des die Verbindung injizierten kastrierten Männchens bzw. des vehikelinjizierten nicht kastrierten Männchens anzeigt.Test Method: Castrated male mice were each with virgin female mice in which V, C, and Vi indicate the average ovarian weights of the intact partners associated with the vehicle-injected castrated male, the compound-injected castrated male, and the vehicle-injected uncastrated male, respectively.
OHOH
OHOH
CH3OCH3O
SC2H5 SC 2 H 5
Reduktion CH3OReduction CH 3 O
SC2H5SC2H5
Eine Lösung von 700mg 16/S-Äthylthio-3,17(S-östradiol-3-methyläther in 160 ml wasserfreiem Äther wird tropfenweise in 280 ml flüssigem Ammoniak unter Kühlung mit Aceton—Trockeneis zugesetzt. Nach Zusatz von 2 g metallischem Lithium wird die erhaltene tiefblaue Mischung während 25 Minuten gerührt, worauf tropfenweise wasserfreies Äthanol zugesetzt wird, bis die Färbung verschwindet. Nach Verdampfung des Ammoniaks schüttelt man die Reaktionsmischung mit Äther. Dann schüttelt man den Ätherextrakt mit 5%iger Kalilauge und hierauf mit Wasser, trocknet und verdampft den Äther. Der farblose viskose. Rückstand wird aus einer Aceton-Petroläther-Mischung zur Kristallisation gebracht, wobei man 434 mg 16JS-Äthylthio-2,5(10)-östradien-3,17/?-diol-3-methyläther als weiße farblose Nadeln mit einem Schmelzpunkt von 130,5 bis 131°C erhält. Ferner ergibt sich [α]" zu +46,9° in Chloroform und yccuzu 3530, 1696 und 1670 cm-1.A solution of 700 mg of 16 / S-ethylthio-3,17 ( S-estradiol-3-methyl ether in 160 ml of anhydrous ether is added dropwise in 280 ml of liquid ammonia while cooling with acetone-dry ice. After adding 2 g of metallic lithium, the The resulting deep blue mixture is stirred for 25 minutes, after which anhydrous ethanol is added dropwise until the color disappears. After the ammonia has evaporated, the reaction mixture is shaken with ether. Then the ether extract is shaken with 5% potassium hydroxide solution and then with water, dried and evaporated .. The ether colorless viscous residue is mixture of acetone-petroleum ether caused to crystallize from a to give 434 mg 16 J S-ethylthio-2,5 (10) -östradien-3,17 /? - diol-3-methyl ether as white colorless needles are obtained with a melting point of 130.5 to 131 ° C. Furthermore, [α] ″ results in + 46.9 ° in chloroform and y ccu as 3530, 1696 and 1670 cm −1 .
Analyse für C21H32O2S:Analysis for C21H32O2S:
Berechnet ... C 72,63%, H 9,25%, S 9,18%;
gefunden ... C 72,30%, H 9,40%, S 8,76%.Calculated ... C 72.63%, H 9.25%, S 9.18%;
found ... C 72.30%, H 9.40%, S 8.76%.
OHOH
CH3OCH 3 O
SC2H5SC2H5
Reduktion, CH3OReduction, CH 3 O
SC2H5SC2H5
Eine Lösung von 400 mg 16ß-äthylthio-3,17ß-östradiol-3-methyläther in 92 ml wasserfreiem Äther und 0,14 ml wasserfreiem Äthanol wird tropfenweise innerhalb 5 Minuten einer Lösung von 0,64 g metallischem Lithium in 80 ml flüssigem Ammoniak unter Aceton-Trockeneis-Kühlung zugesetzt. Hierauf rührt man die erhaltene tiefblaue Mischung während 5 Minuten und setzt tropfenweise wasserfreies Äthanol zu, bis die Färbung verschwindet. Nach Verdampfung des Ammoniaks wird der Rückstand mit Äther geschüttelt. Dann wird der Ätherextrakt mit einer 5 %igen-Kalilauge und hierauf mit Wasser geschüttelt, getrocknet und eingedampft. Den Rückstand aus der Ätherlösung kristallisiert man aus frischem Äther aus, und man erhält 300 mg 16/J-Äthylthio-2,5(10)-östradien-3,17/S-diol-3-methyläther in Form weißer Plättchen mit.einem Schmelzpunkt von 130,5 bis 131,5°C.A solution of 400 mg of 16ß-ethylthio-3,17ß-estradiol-3-methyl ether in 92 ml of anhydrous ether and 0.14 ml of anhydrous ethanol is added dropwise within 5 minutes to a solution of 0.64 g of metallic lithium in 80 ml of liquid ammonia Acetone dry ice cooling added. The deep blue mixture obtained is then stirred for 5 minutes and anhydrous ethanol is added dropwise until the color disappears. After the ammonia has evaporated, the residue is shaken with ether. Then the ether extract is washed with a 5% - potassium hydroxide solution and then shaken with water dried and evaporated. The residue from the ether solution is crystallized from fresh ether, and 300 mg of 16 / I-ethylthio-2,5 (10) -estradiene-3,17 / S-diol-3-methyl ether are obtained in the form of white platelets with Melting point from 130.5 to 131.5 ° C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1224739X | 1962-03-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1224739B true DE1224739B (en) | 1966-09-15 |
Family
ID=14836720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DES84031A Pending DE1224739B (en) | 1962-03-10 | 1963-03-06 | Process for the preparation of 16beta-lower-alkylthio-2, 5 (10) -oestradien-3, 17beta-diol-3-lower alkylthio-ethers |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1224739B (en) |
-
1963
- 1963-03-06 DE DES84031A patent/DE1224739B/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| None * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1445186C3 (en) | 3,3'-di-2-imidazolin-2-yl-carbanilide | |
| DE1695780A1 (en) | Process for the preparation of new N-alkyl-3,1-benzoxain-2-ones | |
| DE1224739B (en) | Process for the preparation of 16beta-lower-alkylthio-2, 5 (10) -oestradien-3, 17beta-diol-3-lower alkylthio-ethers | |
| DE1221228B (en) | Process for the preparation of 5-iodouracil-2'-deoxyriboside-3 ', 5'-di-esters | |
| DE1225173B (en) | Process for the production of 4 (5) - or 5 (10) -OEtrenderivaten | |
| DE1293762B (en) | Adamantanate of testosterone or testosterone derivatives and processes for their production | |
| AT214910B (en) | Process for the preparation of new butyric acid amides substituted on the nitrogen atom and on the β-carbon atom | |
| DE1155436B (en) | Process for the preparation of 1- [p- (ª ‰ -Diaethylaminoaethoxy) -phenyl] -1, 2-diphenyl-2-chloroethylene | |
| AT253141B (en) | Process for the manufacture of new steroids | |
| AT265530B (en) | Process for the preparation of new isoquinoline derivatives | |
| DE972261C (en) | Process for the preparation of dioxopyrazolidine compounds | |
| DE710496C (en) | Process for the production of an ester of crotonic acid betaine (dimethylaminocrotonic acid methyl ester methyl betaine) | |
| DE701956C (en) | Process for obtaining hormone-like substances | |
| DE1768787C3 (en) | (o-Carboxy-phenyl) -acetamidine, process for their preparation and (o-CarboxyphenyO-acetamidine-containing preparations | |
| AT201784B (en) | Process for the preparation of a compound of the cyclopentanopolyhydrophenanthrene series | |
| DE1205095B (en) | Process for the preparation of the hexahydrobenzoate of 2alpha-fluoro-testosterone | |
| DE1027201B (en) | Process for the preparation of compounds having a calming effect on the central nervous system | |
| DE1264432B (en) | Process for the production of new N-3-hydroxypropyl-carbamic acid-beta-hydroxyethyl ester | |
| CH493507A (en) | 1-Beta-methyl-2,3-alpha-methylene androstanes - anabolic agents | |
| DE1216298B (en) | Process for the preparation of 17alpha- (2'-thiazolyl) -17beta-hydroxy-4-androsten-3-one | |
| DE1225637B (en) | Process for the production of steroid 17beta-sulfoacetate esters of the androstane and oestrane series | |
| DE1223373B (en) | Process for the production of testosterone cyclohexyl carbonate | |
| DE1022581B (en) | Process for the preparation of dialkylaminoalkyloxybenzenes | |
| DE1248042B (en) | Process for the production of 17alpha-methyl-17beta-hydroxy-delta 3-5 alpha-androstene and esters | |
| DE1034183B (en) | Process for the production of nor-tropine and nor-ªÎ-tropine esters |