DE1081011B - Process for the preparation of 2,2-dimethyltestosterone derivatives - Google Patents
Process for the preparation of 2,2-dimethyltestosterone derivativesInfo
- Publication number
- DE1081011B DE1081011B DES58673A DES0058673A DE1081011B DE 1081011 B DE1081011 B DE 1081011B DE S58673 A DES58673 A DE S58673A DE S0058673 A DES0058673 A DE S0058673A DE 1081011 B DE1081011 B DE 1081011B
- Authority
- DE
- Germany
- Prior art keywords
- hydrogen
- dimethyltestosterone
- derivatives
- preparation
- acid
- 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 8
- VGKIEZJDYFUUST-KZVLABISSA-N (8r,9s,10r,13s,14s,17s)-17-hydroxy-2,2,10,13-tetramethyl-6,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical class O=C1C(C)(C)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VGKIEZJDYFUUST-KZVLABISSA-N 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 150000001440 androstane derivatives Chemical class 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- -1 steroid alcohols Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 3
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 150000003515 testosterones Chemical class 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 235000010233 benzoic acid 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
- 238000001816 cooling Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940005605 valeric acid Drugs 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
-
- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04B—TRANSMISSION
- H04B1/00—Details of transmission systems, not covered by a single one of groups H04B3/00 - H04B13/00; Details of transmission systems not characterised by the medium used for transmission
- H04B1/06—Receivers
- H04B1/10—Means associated with receiver for limiting or suppressing noise or interference
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Computer Networks & Wireless Communication (AREA)
- Signal Processing (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von 2,2-Dimethyltestosteronderivaten Die Erfindung betrifft ein Verfahren zur Herstellung neuer androgener Hormone der Testosteronreihe, nämlich des 2,2-Dimethyltestosterons und dessen 17a-niedrigen Alkylderivaten bzw. den entsprechenden 17ß-Estern. Die neuen Verbindungen unterscheiden sich dadurch wesentlich von den Verbindungen, die keine 2,2-Dimethylgruppe enthalten, daß sie ein höheres androgen-anabolisches Verhältnis aufweisen. Sie besitzen auch eine Hemmwirkung gegenüber Brustkrebs.Process for the preparation of 2,2-dimethyltestosterone derivatives The invention relates to a process for the production of new androgenic hormones of the testosterone series, namely of 2,2-dimethyltestosterone and its 17a-lower alkyl derivatives or the corresponding 17β-esters. The new connections differ in this substantially different from the compounds that do not contain a 2,2-dimethyl group that they have a higher androgen-anabolic ratio. They also have an inhibitory effect towards breast cancer.
Das erfindungsgemäße Verfahren zur Herstellung von 2,2-Dimethyltestosteronderivaten der allgemeinen Formel worin R für Wasserstoff oder eine niedrige Alkylgruppe und R1 für Wasserstoff oder eine Acylgruppe steht, wobei jedoch mindestens einer der Reste R und R, für Wasserstoff steht, ist nun dadurch gekennzeichnet, daß man in bekannter Weise das entsprechende Androstanderivat durch Behandlung mit etwa lmolaren Äquivalenten Brom in die 4-Monobromverbindung überführt und diese mit einem Bromwasserstoffabspaltungsmittel, vorzugsweise einem tertiären Amin, behandelt.The process according to the invention for the preparation of 2,2-dimethyltestosterone derivatives of the general formula where R is hydrogen or a lower alkyl group and R1 is hydrogen or an acyl group, but at least one of the radicals R and R, is hydrogen, is now characterized in that the corresponding androstane derivative is obtained in a known manner by treatment with about 1 molar equivalents Bromine converted into the 4-monobromo compound and this treated with a hydrogen bromide splitting agent, preferably a tertiary amine.
In der obigen Formel steht R für Wasserstoff und niedrige Alkylgruppen mit weniger als 7 Kohlenstoffatomen, wie z. B. die Methyl-, Äthyl- oder Butylgruppe. R1 steht für Wasserstoff und, falls die Oxygruppe nicht tertiär ist, auch für Reste von Säuren, wie sie üblicherweise zur Veresterung von Steroidalkoholen verwendet werden. Die Säurereste leiten sich im allgemeinen von Kohlenwasserstoffcarbonsäuren mit weniger als 12 C-Atomen ab, wie Essigsäure, Propionsäure, Buttersäure, Valeriansäure, Hexylsäure, Caprylsäure, Hydrocinnamonsäure, Cyclopentylpropionsäure, Benzoesäure usw.In the above formula, R stands for hydrogen and lower alkyl groups with less than 7 carbon atoms, such as. B. the methyl, ethyl or butyl group. R1 stands for hydrogen and, if the oxy group is not tertiary, also for radicals of acids, such as those commonly used for the esterification of steroid alcohols will. The acid residues are generally derived from hydrocarbon carboxylic acids with less than 12 carbon atoms, such as acetic acid, propionic acid, butyric acid, valeric acid, Hexylic acid, caprylic acid, hydrocinnamic acid, cyclopentylpropionic acid, benzoic acid etc.
Das erfindungsgemäße Verfahren kann durch das folgende Schema dargestellt werden: R und R1 stehen dabei, wie oben definiert.The method according to the invention can be represented by the following scheme: R and R1 are as defined above.
Das erfindungsgemäße Verfahren wird durchgeführt, indem man die als Ausgangsprodukt verwendete 2,2-Dimethylandrostan-17ß-ol-3-on-Verbindung (hergestellt gemäß Patent 1055 529) mit wenig mehr als lmolaren Aquivalenten Brom zur Bildung der entsprechenden 4-Bromverbindung umsetzt. Durch Bromwasserstoffabspaltung aus dieser Bromverbindung, beispielsweise mit einem tertiären Amin, wie Collidin, erhält man die entsprechende 44-Androstenverbindung, d. h. das Testosteronderivat.The inventive method is carried out by using the as Starting product used 2,2-dimethylandrostane-17ß-ol-3-one compound (manufactured according to Patent 1055,529) with little more than 1 molar equivalents Reacts bromine to form the corresponding 4-bromine compound. By splitting off hydrogen bromide from this bromine compound, for example with a tertiary amine such as collidine, the corresponding 44-androstene compound is obtained, i. H. the testosterone derivative.
Das nachfolgende Beispiel veranschaulicht das erfindungsgemäße Verfahren.The following example illustrates the method according to the invention.
Beispiel Eine Lösung von 1,lmolaren Äquivalenten Brom in 5 ccm Chloroform wurde tropfenweise und unter ständigem Rühren zu einer Lösung von 1 g 2,2 Dimethylandrostan-17ß-ol-3-on (hergestellt gemäß Patent 1055 529) in 20 ccm Chloroform gefügt; nach ihrer Entfärbung wurde die Lösung mit Wasser, verdünnter Natriumbicarbonatlösung und Wasser gewaschen, über Natriumsulfat getrocknet und unter vermindertem Druck zur Trockne eingedampft, wobei man 4-Brom 2,2-dimethylandrostan-17ß-ol-3-on erhielt.Example A solution of 1.1 molar equivalents of bromine in 5 cc of chloroform was added dropwise and with constant stirring to a solution of 1 g of 2,2 dimethylandrostan-17β-ol-3-one (manufactured according to patent 1055 529) in 20 cc of chloroform; after their discoloration the solution was washed with water, dilute sodium bicarbonate solution and water, dried over sodium sulfate and evaporated to dryness under reduced pressure, 4-bromo 2,2-dimethylandrostan-17β-ol-3-one was obtained.
Dieses Produkt wurde unter Rückfluß während einer Stunde mit 10 ccm Collidin erhitzt. Nach dem Abkühlen wurde das Gemisch mit Äthylacetat verdünnt und filtriert, und die Äthylacetatlösung wurde mit verdünnter Schwefelsäure und Wasser gewaschen, getrocknet und zur Trockne eingedampft. Durch Chromatographieren des Rückstandes erhielt man 500 mg 2,2-Dimethyltestosteron; A.,"" 242 bis 243 mK (log e = 4,14).This product was refluxed at 10 cc for one hour Collidine heated. After cooling, the mixture was diluted with ethyl acetate and filtered, and the ethyl acetate solution was washed with dilute sulfuric acid and water washed, dried and evaporated to dryness. By chromatographing the 500 mg of 2,2-dimethyltestosterone were obtained from the residue; A., "" 242 to 243 mK (log e = 4.14).
Das 17-Acetat von 2,2-Dimethylandrostan-17ß-ol-3-on ergab beim Behandeln mit 1,1molaren Äquivalenten Brom das 17-Acetat von 4-Brom-2,2-dimethylandrostan-17ß-ol-3-on mit einem Schmelzpunkt von 146 bis 148°C; [a]D + 13°. Durch Bromwasserstoffabspaltung aus dieser Verbindung mit Collidin erhielt man das 17-Acetat von 2,2-Dimethyltestosteron mit einem Schmelzpunkt von 171 bis 173°C; [a]D -I- 44°.The 17-acetate of 2,2-dimethylandrostan-17β-ol-3-one gave on treatment with 1.1 molar equivalents of bromine, the 17-acetate of 4-bromo-2,2-dimethylandrostan-17β-ol-3-one having a melting point of 146 to 148 ° C; [a] D + 13 °. By splitting off hydrogen bromide from this combination with collidine, the 17-acetate of 2,2-dimethyltestosterone was obtained with a melting point of 171 to 173 ° C; [a] D -I- 44 °.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MX1081011X | 1956-03-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1081011B true DE1081011B (en) | 1960-05-05 |
Family
ID=19745243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DES58673A Pending DE1081011B (en) | 1956-03-14 | 1957-03-13 | Process for the preparation of 2,2-dimethyltestosterone derivatives |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1081011B (en) |
-
1957
- 1957-03-13 DE DES58673A patent/DE1081011B/en active Pending
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