DE1212083B - Process for the preparation of 20-tert-amino-20-alkyl-5alpha-pregnane compounds and salts thereof - Google Patents
Process for the preparation of 20-tert-amino-20-alkyl-5alpha-pregnane compounds and salts thereofInfo
- Publication number
- DE1212083B DE1212083B DER35993A DER0035993A DE1212083B DE 1212083 B DE1212083 B DE 1212083B DE R35993 A DER35993 A DE R35993A DE R0035993 A DER0035993 A DE R0035993A DE 1212083 B DE1212083 B DE 1212083B
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- Prior art keywords
- hydroxy
- alkyl
- pregnen
- methyl
- amino
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
-
- 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
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- 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
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
Int. Cl.:Int. Cl .:
C07cC07c
Deutsche Kl.: 12 ο-25/05German class: 12 ο-25/05
Nummer: 1 212 083 Number: 1 212 083
Aktenzeichen: R 35993IV b/12 ο File number: R 35993 IV b / 12 ο
Anmeldetag: 27. August 1963 Filing date: August 27, 1963
Auslegetag: 10. März 1966Opening day: March 10, 1966
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen 20-tert.-Amino-20-alkyl-5«-pregnanverbindungen der allgemeinen Formel IThe invention relates to a process for the preparation of new 20-tert-amino-20-alkyl-5 "-pregnane compounds of the general formula I.
in Form der freien Basen oder entsprechender Salze. In dieser Formel bedeuten R und R1 niedere Alkylreste, Aryl- oder Aralkylreste, R2 bedeutet einen Alkylrest mit 1 bis 4 Kohlenstoffatomen, X stellt die Gruppein the form of the free bases or corresponding salts. In this formula, R and R 1 denote lower alkyl radicals, aryl or aralkyl radicals, R 2 denotes an alkyl radical having 1 to 4 carbon atoms, and X represents the group
.-H.-H
OR3 OR 3
dar, und R3 bezeichnet Wasserstoff oder einen niederen, gegebenenfalls substituierten Acylrest.represents, and R 3 denotes hydrogen or a lower, optionally substituted acyl radical.
Die neuen Verbindungen besitzen interessante physiologische Eigenschaften, vor allem eine vasodilatatorische, spasmolytische und insbesondere koronardilatatorische Wirkung.The new compounds have interesting physiological properties, especially a vasodilator, spasmolytic and especially coronary dilatatory effects.
Unter diesen Verbindungen ist das 3/3-Hydroxy-20-methyl-20-dimethylamino-5a-pregnan von besonderem Interesse.Among these compounds is the 3/3-hydroxy-20-methyl-20-dimethylamino-5a-pregnane of special interest.
Die angewandte Dosierung dieser Verbindungen bewegt sich zwischen 5 und 20 mg je Dosis und 10 bis 100 mg je Tag beim Erwachsenen, je nach der Art der Verabreichung.The applied dosage of these compounds ranges between 5 and 20 mg per dose and 10 to 100 mg per day for adults, depending on the route of administration.
Das erfindungsgemäße Verfahren zur Herstellung der Verbindungen der allgemeinen Formel I zeichnet
sich dadurch aus, daß man in an sich bekannter Weise ein primäres Amin der Formel NH2R, worin
R die vorstehend angegebene Bedeutung hat, mit 3/?-Hydroxy-20-oxo-zj 5-pregnen reagieren läßt, das
gebildete 20-Iminoderivat durch Behandlung mit einem niederen Alkyl-, einem Aryl- oder Aralkylhalogenid
der Formel Hai — R1, worin Hai ein Halogenatom
bedeutet und R1 die vorstehend angegebene Bedeutung hat, zum ternären Iminiumsalz umsetzt, das erhaltene
Salz mit einem Alkylmagnesiumhalogenid der Formel Hai — MgR2, worin Hai ein Halogenatom bedeutet
und R2 die vorstehend angegebene Bedeutung hat, Verfahren zur Herstellung von 20-tert.-Amino-20-alkyl-5a-pregnanverbindungen
und Salzen
derselbenThe process according to the invention for the preparation of the compounds of the general formula I is characterized in that, in a manner known per se, a primary amine of the formula NH 2 R, in which R has the meaning given above, is treated with 3 /? -Hydroxy-20-oxo -zj 5 -pregnen can react, the 20-imino derivative formed by treatment with a lower alkyl, an aryl or aralkyl halide of the formula Hai - R 1 , in which Hai is a halogen atom and R 1 has the meaning given above, to the ternary iminium salt reacted, the salt obtained with an alkyl magnesium halide of the formula Hai - MgR 2 , in which Hai is a halogen atom and R 2 has the meaning given above, a process for the preparation of 20-tert-amino-20-alkyl-5a-pregnane compounds and salts
the same
Anmelder:Applicant:
Roussel-Uclaf, ParisRoussel-Uclaf, Paris
Vertreter:Representative:
Dr. F. Zumstein,Dr. F. Zumstein,
Dipl.-Chem. Dr. rer. nat. E. AssmannDipl.-Chem. Dr. rer. nat. E. Assmann
und Dipl.-Chem. Dr. R. Koenigsberger,and Dipl.-Chem. Dr. R. Koenigsberger,
Patentanwälte, München 2, Bräuhausstr. 4Patent Attorneys, Munich 2, Bräuhausstr. 4th
Als Erfinder benannt:
Dr.-Ing. Daniel Bertin, Montrouge, Seine;
Dr. Lucien Nedelec, Clichy-sur-Bois,
Seine-et-Oise (Frankreich)Named as inventor:
Dr.-Ing. Daniel Bertin, Montrouge, Seine;
Dr. Lucien Nedelec, Clichy-sur-Bois,
Seine-et-Oise (France)
Beanspruchte Priorität:
Frankreich vom 27. August 1962 (907 856),
vom 3. Mai 1963 (933 624)Claimed priority:
France of August 27, 1962 (907 856),
of May 3, 1963 (933 624)
umsetzt, das erhaltene 3/?-Hydroxy-20-alkyl-20-tert.- amino-Δ 5-pregnen nach vorübergehender Salzbildung isoliert, die in 5 (6)-Stellung vorhandene Doppelbindung durch katalytische Hydrierung reduziert, gegebenenfalls die Hydroxylfunktion in 3-Stellung acyliert und dann gegebenenfalls die erhaltene Verbindung in ein Salz einer Mineralsäure oder einer organischen Säure überführt.implemented, the 3 /? - Hydroxy-20-alkyl-20-tert-amino- Δ 5 -pregnen isolated after temporary salt formation, the double bond present in the 5 (6) position is reduced by catalytic hydrogenation, optionally the hydroxyl function in 3 -Position acylated and then optionally converted the compound obtained into a salt of a mineral acid or an organic acid.
Zur Herstellung des oben angegebenen Produktes, 3/3-Hydroxy-20-methyl-20-dimethylamino-5Ä-pregnan arbeitet man wie folgt:To make the above product, 3/3-Hydroxy-20-methyl-20-dimethylamino-5Ä-pregnane work as follows:
Man setzt das 3/3-Hydroxy-20-oxo-J 5-pregnen mit Methylamin in Gegenwart von Natriummethylat um; das erhaltene 20-Methyliminoderivat überführt man durch Behandlung mit Methyljodid in das entsprechende Jodmethylat, läßt dieses mit Methylmagnesiumbromid reagieren, erhält 3/3-Hydroxy-20-methyl-20-dimethylamino-/J B-pregnen, das man durch katalytische Hydrierung reduziert unter Bildung des 3^-Hydroxy-20-methyI-20-dimethylamino-5iX-pregnans. The 3/3-hydroxy-20-oxo-J 5 -pregnene is reacted with methylamine in the presence of sodium methylate; the 20-methylimino derivative obtained is converted into the corresponding iodine methylate by treatment with methyl iodide, this is allowed to react with methylmagnesium bromide, 3/3-hydroxy-20-methyl-20-dimethylamino- / J B -pregnen is obtained, which is reduced by catalytic hydrogenation Formation of the 3 ^ -hydroxy-20-methyI-20-dimethylamino-5iX-pregnane.
Das folgende Beispiel erläutert das Verfahren der Erfindung.The following example illustrates the method of the invention.
609 537/441609 537/441
1212 Q831212 Q83
3 43 4
Beispiel 1 gelöst in. 60-ccm ,Wasser, und erhitzt .1 Stunde aufExample 1 dissolved in 60 ccm water and heated for 1 hour
υ I1 " 80° C. Man versetzt mit Natronlauge bis zum pH 10,υ I 1 "80 ° C. Sodium hydroxide solution is added up to pH 10,
™-ua ™ *uT™a-SVT, '· "ii gießt in 2400ecm Wasser und kühlt 1 Stunde. Man ™ -ua ™ * uT ™ a- SV T, '· "ii Pour into 2400 cm of water and cool for 1 hour
3^-Hydroxy-20-methyl-20-dimethylammoallopregnan extrahiert den gebildeten Niederschlag mit Äther,3 ^ -Hydroxy-20-methyl-20-dimethylammoallopregnan extracted the precipitate formed th with ether,
Stufe A: 5 wäscht mit Wasser, trocknet über Magnesiumsulfat,Stage A: 5 washes with water, dries over magnesium sulfate,
3/?-Hydroxy-20-methylimmo-zl «-pregnan leitet ü?fr Tierkohle, filtriert und sättigt mit gasförmi-3 /? - hydroxy-20-methyl-immo zl "pregnan passes ü f r Tie rkohle, filtered and saturated with gaseous?
gem Chlorwasserstoff.according to hydrogen chloride.
Man kühlt eine Lösung von 200 ecm Monomethyl- Man erhält 15,813 g rohes Chlorhydrat von 3/J-Hy-A solution of 200 ecm monomethyl is cooled. 15.813 g of crude hydrochloride of 3 / J-Hy-
amin in 240 ecm Methanol auf — 10°.C ab und gibt droxy-20-methyl-20-dimethylamino-/d5-pregnen (F.amine in 240 ecm of methanol to -10 ° C and gives droxy-20-methyl-20-dimethylamino- / d 5 -pregnen (F.
50 g 3/?-Hydroxy-20-oxo-/45-pregnen"und 12 g Na- io =245 bis 25O0C), das man in 180 ecm Methanol50 g 3 /? - Hydroxy-20-oxo- / 4 5 -pregnen "and 12 g Na- io = 245 to 250 0 C), which one in 180 ecm of methanol
triummethylat zu. Man versetzt mit 10 ecm Methanol löst und mit einer Natronlaugelösung bis zum pH 8trium methylate to. It is mixed with 10 ecm of methanol and dissolved with a sodium hydroxide solution up to pH 8
und erhitzt die Reaktionsmischung unter Druck eine bis 9 versetzt.and heated the reaction mixture under pressure from one to nine.
Nacht unter Rühren auf 100° C. Man fügt 400 ecm Methanol zu, engt ein, kühlt,Night with stirring to 100 ° C. 400 ecm of methanol are added, the mixture is concentrated, and the mixture is cooled,
Man kühlt auf — 10° C ab, saugt die gebildeten saugt ab, wäscht, trocknet im Trockenschrank undIt is cooled to -10 ° C., the formed sucks off, washed, dried in a drying cabinet and
Kristalle ab, wäscht mit eisgekühltem Methanol, mit 15 erhält 12,685 g 3/?-Hydroxy-20-methyl-20-dimethyl-Crystals off, washed with ice-cold methanol, with 15 you get 12.685 g of 3 /? - Hydroxy-20-methyl-20-dimethyl-
wäßrigem Methanol und mit Wasser und trocknet. amino-Zl 5-pregnen vom F. = 170° C, [α]?? = —65±1°aqueous methanol and with water and dry. amino-Zl 5 -pregnen from mp = 170 ° C, [α] ?? = -65 ± 1 °
Nach Umkristallisieren aus Methanol erhält man 23 g (c = 1%, Tetrahydrofuran) in einer Ausbeute vonAfter recrystallization from methanol, 23 g (c = 1%, tetrahydrofuran) are obtained in a yield of
3/S-Hydroxy-20-methylimino-id5-pregnen vom F. 57,5%.3 / S-Hydroxy-20-methyliminoid 5 -pregnen from F. 57.5%.
= 230° C, [α]?? = —17,5 ±2° (c = 0,5% ,Tetra- Das Produkt ergibt sich in Form von farblosen= 230 ° C, [α] ?? = -17.5 ± 2 ° (c = 0.5%, Tetra- The product results in the form of colorless
hydrofuran). Ausbeute = 44,2 %. 20 Kristallen, die in verdünnten Säuren, Äther, Benzolhydrofuran). Yield = 44.2%. 20 crystals contained in dilute acids, ethers, benzene
Das Produkt ergibt sich in Form von farblosen und Chloroform wenig löslich und in Wasser, ver-The product results in the form of colorless and chloroform and is sparingly soluble in water,
Kristallen, die in Alkohol, Aceton und Chloroform dünnten Alkalien und Aceton unlöslich sind.Crystals that are insoluble in alcohol, acetone and chloroform, dilute alkalis and acetone.
wenig löslich und in Wasser, verdünnten Säuren und a^i,«.«. r> υ xrr\ isa « An 1· ϊ.ι 1 T-> 1 1.. 1· 1 · ϊ Analyse. ^04JnUi1INU — ojy,jo.sparingly soluble and in water, dilute acids and a ^ i, «.«. r> υ xrr \ isa «An 1 · ϊ.ι 1 T-> 1 1 .. 1 · 1 · ϊ Analysis. ^ 04JnUi 1 INU - ojy, jo.
Alkahen, Äther und Benzol unlöslich smd. ^^ Q ^15 ^ R ^49 ^ N ^ %.Alkali, ether and benzene are insoluble. ^^ Q ^ 15 ^ R ^ 49 ^ N ^ % .
Analyse: C22H35NO = 329,52. "b gefunden .... C 80,4%, H 11,2%, N 4,3%.Analysis: C 22 H 35 NO = 329.52. " b found .... C 80.4%, H 11.2%, N 4.3%.
Berechnet .... C 80,19 %, H 10,71 %, N 4,25 %; Das Produkt ^1nJ6 in der Literatur bisher noch nichtCalculated .... C 80.19%, H 10.71%, N 4.25%; The product ^ 1n J 6 has not yet been found in the literature
gefunden .... C 80,1%, H 10,4%, N 4,2%. beschrieben.found .... C 80.1%, H 10.4%, N 4.2%. described.
Die Verbindung wurde in der Literatur bisher noch Stufe D:The connection was still level D in the literature:
nicht beschrieben. 30 .not described. 30th
_ Sp-Hydroxy^O-methyl^O-dimethylammoallopregnan_ Sp-Hydroxy ^ O-methyl ^ O-dimethylammoallopregnan
T j ., , ■ ,ο TT j ->« ti·· Man hydriert eine Mischung von 2 g 3/3-Hydroxy- T j.,, ■, ο TT j -> «ti ·· A mixture of 2 g of 3/3-hydroxy-
Jodmethylat von ^-Hydroxy^O-methylimmo- 20-methyl-20-dimethylamino-zl«-pregnen und 70 ecmIodomethylate of ^ -hydroxy ^ O-methylimmo-20-methyl-20-dimethylamino-zl «-pregnen and 70 ecm
"Pregnen Essigsäure unter Anwesenheit von 400 mg Platindioxyd"P re g NEN acetic acid in the presence of 400 mg Platindioxyd
Man gibt 23 g 3jS-Hydroxy-20-methylimino-id 5-pre- 35 in 12 ecm Essigsäure. Nach einer Stunde stellt man das23 g of 3JS-hydroxy-20-methyliminoid 5 -pre- 35 are added to 12 ecm acetic acid. After an hour you set that
gnen in 400 ecm. Chloroform, destilliert 40 ecm des Einleiten von Wasserstoff ein, filtriert, wäscht dengnen in 400 ecm. Chloroform, distilled in 40 ecm of the introduction of hydrogen, filtered, washed the
Lösungsmittels ab, versetzt mit 80 ecm Methyljodid Katalysator mit Essigsäure und dampft die FiltrateSolvent from, treated with 80 ecm methyl iodide catalyst with acetic acid and the filtrates evaporated
und bringt zwei Stunden zum Rückfluß. Man kühlt zur Trockne ein.and reflux for two hours. One cools to dryness.
auf Eis, saugt den Niederschlag ab, wäscht mit Chloro- Man versetzt den Rückstand mit 120 ecm Methanolon ice, the precipitate is filtered off with suction, washed with chlorine. 120 ecm of methanol are added to the residue
form und mit Äther und .trocknet. Man erhält so 4° und 10 ecm konzentrierter Natronlauge und läßt unterform and with ether and .dry. This gives 4 ° and 10 ecm of concentrated sodium hydroxide solution and leaves it undone
29,8 g rohes Jodmethylat von 3^-Hydroxy-20-methyl- Rühren in Stickstoffatmosphäre 2 Stunden stehen.29.8 g of crude iodine methylate of 3 ^ -hydroxy-20-methyl- stand stirring in a nitrogen atmosphere for 2 hours.
imino-/l 5-pregnen, das so, wie es ist, für die folgende Man saugt ab, wäscht mit Wasser und trocknet imimino- / l 5 -pregnen, as it is, for the following man sucks off, washed with water and dries in the
Verfahrensstufe verwendet wird. F.,.= 280°C (Zer- Vakuum. Man löst in Methanol, leitet über Tierkohle,Process stage is used. F.,. = 280 ° C (Zer- vacuum. Dissolve in methanol, pass over animal charcoal,
Setzung). Ausbeute = 90,5%. filtriert, konzentriert, kühlt, saugt ab, wäscht mitSettlement). Yield = 90.5%. filtered, concentrated, cools, sucks off, washes with
Das Produkt ergibt sich in Form von weißen 45 Methanol und erhält 1,812 g 3/?-Hydroxy-20-methyl-The product is obtained in the form of white methanol and contains 1.812 g of 3 /? - hydroxy-20-methyl-
Kristallen, die in Alkohol und Benzol wenig löslichund 20-dimethylaminoallopregnan vom F. = 175° C,Crystals which are sparingly soluble in alcohol and benzene and 20-dimethylaminoallopregnane with a temperature of 175 ° C,
in Wasser, verdünnten Säuren und Alkalien, Äther, [oc\2S = +3 ± 1,5° (c = 1 %, Tetrahydrofuran) inin water, dilute acids and alkalis, ether, [oc \ 2 S = +3 ± 1.5 ° (c = 1%, tetrahydrofuran) in
Aceton und Chloroform unlöslich sind. einer Ausbeute von 90 %.Acetone and chloroform are insoluble. a yield of 90%.
Analyse· C H -TNO = 471 47 ^as P^ukt ergibt sich in Form von farblosenAnalysis · CH -TNO = 471 47 ^ as the point results in the form of colorless
^ , 23^t8O -An/ TT η '«λ/" T ^ «-,„ / -vt^^^a, 5° Kristallen, die in verdünnten Säuren, Alkoholen, Äther^, 23 ^ t 8 O -An / TT η '«λ /" T ^ "-," / -vt ^^^ a, 5 ° Crystals in dilute acids, alcohols, ethers
Berechnet C 58 59%, H 8,0%, J 26,92%, N 2,97 %; ^ ^n weni löslich und in w^sser und ye;dünn.Calculated C 58 59%, H 8.0%, J 26.92%, N 2.97%; ^ ^ n less soluble and in w ^ sser and ye ; thin .
gefunden C 58,3,"/0, H 8,0»/0, J 27,0%, N 2,6%. ten Alkalien unlöslich sind.found C 58.3, "/ 0 , H 8.0» / 0 , I 27.0%, N 2.6%. the alkalis are insoluble.
Das Produkt wurde in der Literatur bisher noch nicht Analvse· C H NO = 361 58The product has not yet been analyzed in the literature.C H NO = 361 58
beschrieben. Berechnet4. !*.. C 79,71%, H 11,99«/„, N 3,8%;described. Calculates 4 . ! * .. C 79.71%, H 11.99 "/", N 3.8%;
btuIeC· gefunden .... C 80,0%, H 12,0%, N 3,87%. btuIeC · found .... C 80.0%, H 12.0%, N 3.87%.
3^-Hydroxy-20-methyl-20-dimethylamino-Zl«-pregnen Das Produkt wurde in der Literatur bisher noch nicht3 ^ -Hydroxy-20-methyl-20-dimethylamino-Zl «-pregnen The product has not yet been in the literature
Man gibt 280 ecm einer 3,2 molaren ätherischen beschrieben.One gives 280 ecm of a 3.2 molar essential described.
Lösung von Methylmagnesiumbromid in 400ecm Beispiel 2Solution of methyl magnesium bromide in 400ecm Example 2
Tetrahydrofuran, versetzt langsam mit 28,8 g des 6o ■ :Tetrahydrofuran, slowly mixed with 28.8 g of the 6o ■:
in Stufe B erhaltenen Produktes, bringt die Reaktions- oo TT J Heri*ellung des Hydrochloride desproduct obtained in stage B, brings the reaction oo TT J Her i * ellun g of the hydrochloride des
mischung unter Stickstoffatmosphäre eine Nacht zum 3/J-Hydroxy-2(^meÜiyl-20-dimeÜiylaiiuno-5«-pregnans Rückfluß und gießt in ein Gemisch von 2400 ecm Eis Man löst 1 g des nach Beispiel 1 erhaltenen 3/9-Hy-Mixture under a nitrogen atmosphere for one night to give 3 / I-hydroxy-2 (^ meÜiyl-20-dimÜiylaiiuno-5 "-pregnans Reflux and poured into a mixture of 2400 ecm of ice. 1 g of the 3/9 Hy-
und Wasser, 240 g Ammoniumchlorid und 320 ecm droxy-20-methyl-20-dimethylamino-5«-pregnans in konzentriertem Ammoniak. .- 55 20ccm Isopropanol, kühlt auf Eis und fügt unter Rührenand water, 240 g of ammonium chloride and 320 ecm of hydroxy-20-methyl-20-dimethylamino-5 "-pregnans in concentrated ammonia. .- 55 20ccm isopropanol, cools on ice and adds while stirring
Man filtriert das erhaltene Produkt, wäscht mit 3,5 ecm Äther, der mit Salzsäure gesättigt ist, zu.The product obtained is filtered off and washed with 3.5 ecm of ether which is saturated with hydrochloric acid.
Wasser und versetzt mit 25 ecm Methanol und dann Man rührt den. voluminösen Niederschlag etwaWater and mixed with 25 ecm of methanol and then stirred. voluminous rainfall about
mit 52 ecm Essigsäure und 52 g Natriumacetat, 15 Minuten, trennt ihn durch Filtration ab, saugt abwith 52 ecm of acetic acid and 52 g of sodium acetate, 15 minutes, separates it off by filtration, sucks it off
und wäscht mit Äther. Man erhält 1,2 g des Hydrochlorids, mit einem Schmelzpunkt von ungefähr bis 2300C.and washes with ether. 1.2 g of the hydrochloride are obtained, with a melting point of approximately up to 230 ° C.
Man reinigt das Hydrochlorid durch Anteigen mit ecm warmem Isopropanol. Auf diese Weise erhält man 0,95 g des reinen Hydrochloride, das bei etwa bis 2500C schmilzt.The hydrochloride is purified by pasting with ecm warm isopropanol. In this way, 0.95 g of the pure hydrochloride, which melts at about up to 250 ° C., is obtained.
Claims (2)
USA.-Patentschrift Nr. 3 013 008.Considered publications:
U.S. Patent No. 3,013,008.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR907856A FR1421231A (en) | 1962-08-27 | 1962-08-27 | New amino steroids and method of preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
DE1212083B true DE1212083B (en) | 1966-03-10 |
Family
ID=8785774
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DER35992A Pending DE1212082B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 3, 11-Dioxo-20-tert-amino-20-alkyl-4-pregnenverbindungen and salts thereof |
DER35990A Pending DE1212080B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 20-tert-amino-20-alkyl steroids and salts thereof |
DER35993A Pending DE1212083B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 20-tert-amino-20-alkyl-5alpha-pregnane compounds and salts thereof |
DER35991A Pending DE1212081B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 11-oxo-20-tert-amino-20-alkyl-5beta-pregnane compounds and salts thereof |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DER35992A Pending DE1212082B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 3, 11-Dioxo-20-tert-amino-20-alkyl-4-pregnenverbindungen and salts thereof |
DER35990A Pending DE1212080B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 20-tert-amino-20-alkyl steroids and salts thereof |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DER35991A Pending DE1212081B (en) | 1962-08-27 | 1963-08-27 | Process for the preparation of 11-oxo-20-tert-amino-20-alkyl-5beta-pregnane compounds and salts thereof |
Country Status (6)
Country | Link |
---|---|
BE (1) | BE636641A (en) |
DE (4) | DE1212082B (en) |
ES (1) | ES290991A1 (en) |
FR (3) | FR1421231A (en) |
GB (4) | GB1025906A (en) |
NL (4) | NL297133A (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3013008A (en) * | 1961-01-09 | 1961-12-12 | Searle & Co | N-substituted 20-aminopregnan-3-ols, esters thereof, and deta-derivatives corresponding |
-
0
- NL NL297135D patent/NL297135A/xx unknown
- BE BE636641D patent/BE636641A/xx unknown
- NL NL297131D patent/NL297131A/xx unknown
- NL NL123751D patent/NL123751C/xx active
- NL NL297133D patent/NL297133A/xx unknown
-
1962
- 1962-08-27 FR FR907856A patent/FR1421231A/en not_active Expired
- 1962-11-27 FR FR916749A patent/FR2374M/en not_active Expired
-
1963
- 1963-05-03 FR FR933624A patent/FR56F/en not_active Expired
- 1963-08-22 ES ES290991A patent/ES290991A1/en not_active Expired
- 1963-08-27 DE DER35992A patent/DE1212082B/en active Pending
- 1963-08-27 GB GB3393663A patent/GB1025906A/en not_active Expired
- 1963-08-27 DE DER35990A patent/DE1212080B/en active Pending
- 1963-08-27 GB GB3393863A patent/GB1025908A/en not_active Expired
- 1963-08-27 DE DER35993A patent/DE1212083B/en active Pending
- 1963-08-27 DE DER35991A patent/DE1212081B/en active Pending
- 1963-08-27 GB GB3393763A patent/GB1025907A/en not_active Expired
-
1965
- 1965-04-14 GB GB1601065A patent/GB1045644A/en not_active Expired
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3013008A (en) * | 1961-01-09 | 1961-12-12 | Searle & Co | N-substituted 20-aminopregnan-3-ols, esters thereof, and deta-derivatives corresponding |
Also Published As
Publication number | Publication date |
---|---|
ES290991A1 (en) | 1963-12-01 |
NL297133A (en) | |
GB1025906A (en) | 1966-04-14 |
BE636641A (en) | |
DE1212081B (en) | 1966-03-10 |
FR2374M (en) | 1964-04-03 |
NL297131A (en) | |
FR1421231A (en) | 1965-12-17 |
GB1025907A (en) | 1966-04-14 |
NL123751C (en) | |
DE1212082B (en) | 1966-03-10 |
FR56F (en) | 1964-10-16 |
GB1025908A (en) | 1966-04-14 |
GB1045644A (en) | 1966-10-12 |
NL297135A (en) | |
DE1212080B (en) | 1966-03-10 |
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