DD258820A1 - PROCESS FOR PREPARING 6BETA-HYDROXY-METHYL-ANDROSTA-1,4-DIEN-3,17-DION - Google Patents
PROCESS FOR PREPARING 6BETA-HYDROXY-METHYL-ANDROSTA-1,4-DIEN-3,17-DION Download PDFInfo
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- DD258820A1 DD258820A1 DD29127686A DD29127686A DD258820A1 DD 258820 A1 DD258820 A1 DD 258820A1 DD 29127686 A DD29127686 A DD 29127686A DD 29127686 A DD29127686 A DD 29127686A DD 258820 A1 DD258820 A1 DD 258820A1
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- German Democratic Republic
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- dione
- diene
- dien
- hydroxymethyl
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Abstract
Es wird ein Verfahren zur Herstellung von 6b-Hydroxymethyl-androsta-1,4-dien-3,17-dion beschrieben, welches eine bisher nicht bekannte Verbindung darstellt, die auf Grund verschiedener reaktiver Zentren im Molekuel als Zwischenprodukt zur Herstellung von Steroidpharmaka genutzt werden kann.A process is described for the preparation of 6b-hydroxymethyl-androsta-1,4-diene-3,17-dione, which is a hitherto unknown compound which, because of various reactive centers in the molecule, is used as an intermediate for the production of steroidal drugs can.
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1). Diese Verbindung ist ein neues, bisher nicht beschriebenes Steroidderivat und kann auf Grund verschiedener reaktiver Zentren im Molekül als Zwischenprodukt zur Herstellung von Steroidpharmaka eingesetzt werden.The invention relates to a process for the preparation of 6β-hydroxymethyl-androsta-1,4-diene-3,17-dione (1). This compound is a novel, previously undescribed steroid derivative and can be used as an intermediate for the production of steroid drugs due to various reactive centers in the molecule.
Ein Verfahren zur Herstellung von 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1) ist in der Literatur bisher nicht beschrieben. Die Verbindung ist in Chemical Abstracts nicht referiert. Es ist ein Verfahren bekannt, welches zur Darstellung einef analogen Verbindung ohne 1-Doppelbindung,dem 6ß-Hydroxymethyl-androst-4-en-3,17-dion (2), eingesetzt wurde (Schneider, E. et al. HeIv. Chim. Acta 56 [1973] 2396). Dabei wird Androst-4-en-3,17-dion (3) zunächst mit Pyrrolidin in das Enamin (4) überführt und dieses durch Umsetzung mit Formaldehyd bei Raumtemperatur in ein Gemisch von 6ß-Hydroxymethyl-androst-4-en-3,17-dion (2) und 6ß-Hydroxy-androst-4-en-3,17-dion (5) verwandelt.A process for the preparation of 6β-hydroxymethyl-androsta-1,4-diene-3,17-dione (1) has not previously been described in the literature. The compound is not reported in Chemical Abstracts. There is known a method which has been used to prepare an analogous compound having no 1-double bond, 6β-hydroxymethyl-androst-4-ene-3,17-dione (2) (Schneider, E. et al., HeIv. Chim Acta 56 [1973] 2396). Androst-4-ene-3,17-dione (3) is first converted with pyrrolidine into the enamine (4) and this by reaction with formaldehyde at room temperature in a mixture of 6ß-hydroxymethyl-androst-4-en-3, 17-dione (2) and 6β-hydroxy-androst-4-ene-3,17-dione (5).
Durch säulenchromatographische Trennung dieses Gemisches an Kieselgel erhält man 22% 6ß-Hydroxymethyl-androst-4-en-3,17-dion (2) und 28% 6ß-Hydroxy-androst-4-en-3,17-dion (5).Column chromatography on silica gel gives 22% of 6β-hydroxymethyl-androst-4-ene-3,17-dione (2) and 28% of 6β-hydroxy-androst-4-ene-3,17-dione (5). ,
Ziel der Erfindung ist ein Verfahren, das die Synthese von 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1) in guter Ausbeute und mit geringem chemischen Aufwand gestattet.The aim of the invention is a process which allows the synthesis of 6β-hydroxymethyl-androsta-1,4-diene-3,17-dione (1) in good yield and with little chemical effort.
Der Erfindung liegt die Aufgabe zugrunde, ein Verfahren anzugeben, um 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1) aus einem leicht zugänglichen Ausgangsprodukt auf einfache Weise in guter Ausbeute zu gewinnen.The invention has for its object to provide a method to win 6ß-hydroxymethyl-androsta-1,4-diene-3,17-dione (1) from an easily accessible starting material in a simple manner in good yield.
Erfindungsgemäß wird die Aufgabe dadurch gelöst, daß das leicht zugängliche Androsta-1,4-dien-3,17-dion (6) nach einemAccording to the invention the object is achieved in that the readily available androsta-1,4-diene-3,17-dione (6) after a
Verfahren von Bucourt und Du be (Bull. soc. Chim. Fr. 1978 Pt. 233) in das bekannte !,S-Dipyrolichino-androsta-S^-dien-^-on (7) überführt wird. Dieses wird mit Formaldehyd in einem Lösungsmittelgemisch in 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1) umgesetzt.Bucourt and Du be (Bull Soc. Chim., Fr., 1978, Pt. 233) is converted into the known, S-dipyrolichino-androsta-S-diene-one (7). This is reacted with formaldehyde in a solvent mixture in 6β-hydroxymethyl-androsta-1,4-diene-3,17-dione (1).
Eine vorteilhafte Verfahrensvariante ist die Verwendung von wäßriger Formaldehydlösung, vorzugsweise 30%iger Formaldehydlösung, in einem Lösungsmittelgemisch aus Benzen und Ethanol, vorzugsweise bei einem Mischungsverhältnis von 1:2 und Umsetzung bei Raumtemperatur. Dabei entsteht überraschenderweise das gewünschte 6ß-Hydroxymethylandrosta-1,4-dien-3,17-dion (1) unter gleichzeitiger Abspaltung beider Pyrrolidino-Gruppen in hoher Ausbeute (S 95%):An advantageous variant of the method is the use of aqueous formaldehyde solution, preferably 30% formaldehyde solution, in a solvent mixture of benzene and ethanol, preferably at a mixing ratio of 1: 2 and reaction at room temperature. Surprisingly, the desired 6β-hydroxymethylandrosta-1,4-diene-3,17-dione (1) is formed with simultaneous cleavage of the two pyrrolidino groups in high yield (S 95%):
Die auch bei diesem Verfahren gebildete 6ß-Hydroxy-Verbindung spielt prozentual eine sehr untergeordnete Rolle und kann durch einmalige Kristallisation entfernt werden.The 6β-hydroxy compound also formed in this process plays a very minor percentage and can be removed by a single crystallization.
3,5g Enamin (7) (8,2 mMol) werden in einem Gemisch aus 80 ml Benzen und 160 ml abs. Ethanol gelöst und nach Zusatz von 2,3ml 30% wässriger Formaldehydlösung (24,4mMol) unter Argon bis zur völligen Umsetzung (DC-Kontrolle) gerührt. Danach wird das Reaktionsgemisch im Vakuum zur Trockne gebracht, der Rückstand mit Benzen aufgenommen und die entstandene Lösung mit verd. H2SO4 ausgeschüttelt (restlose Entfernung des aus dem Enamin abgespaltenen Pyrrolidins). Nach Trocknen mit wasserfreiem Na2CO3 und Einengen kristallisiert das 6ß-Hydroxymethyl-androsta-1,4-dien-3,17-dion (1) aus. Ausbeute: 2,4g = 94,5% Fp.: 193"C bis 196°C (aD) +93° Analyse3.5 g of enamine (7) (8.2 mmol) are dissolved in a mixture of 80 ml of benzene and 160 ml of abs. Dissolved ethanol and stirred after addition of 2.3 ml of 30% aqueous formaldehyde solution (24.4 mmol) under argon until complete reaction (TLC control). Thereafter, the reaction mixture is brought to dryness in vacuo, the residue taken up with benzene and the resulting solution with dil. H 2 SO 4 shaken (complete removal of the cleaved from the enamine pyrrolidine). After drying with anhydrous Na 2 CO 3 and concentration, the 6β-hydroxymethyl-androsta-1,4-diene-3,17-dione (1) crystallizes out. Yield: 2.4 g = 94.5% mp. 193 "C to 196 ° C (a D ) + 93 ° analysis
6-CH2-O6-CH 2 -O
3,89 3,813.89 3.81
Claims (4)
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Application Number | Priority Date | Filing Date | Title |
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DD29127686A DD258820A1 (en) | 1986-06-13 | 1986-06-13 | PROCESS FOR PREPARING 6BETA-HYDROXY-METHYL-ANDROSTA-1,4-DIEN-3,17-DION |
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DD29127686A DD258820A1 (en) | 1986-06-13 | 1986-06-13 | PROCESS FOR PREPARING 6BETA-HYDROXY-METHYL-ANDROSTA-1,4-DIEN-3,17-DION |
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DD258820A1 true DD258820A1 (en) | 1988-08-03 |
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DD29127686A DD258820A1 (en) | 1986-06-13 | 1986-06-13 | PROCESS FOR PREPARING 6BETA-HYDROXY-METHYL-ANDROSTA-1,4-DIEN-3,17-DION |
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Cited By (5)
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WO2008137048A1 (en) | 2007-05-04 | 2008-11-13 | Scinopharm Taiwan, Ltd. | Process for preparing aromatase inhibitors |
EP2099460A2 (en) * | 2006-11-30 | 2009-09-16 | Endece, LLC | 6-alkoxyalkyl estradiol derivatives and methods of use |
WO2011066542A2 (en) | 2009-11-30 | 2011-06-03 | Endece Inc. | 6-substituted estradiol derivatives and methods of use |
US8183401B2 (en) | 2004-01-16 | 2012-05-22 | Cedarburg Pharmaceuticals, Inc. | Exemestane and its intermediates and methods of making the same |
US9422324B2 (en) | 2010-09-14 | 2016-08-23 | Endece Llc | 6-substituted demethyl-estradiol derivatives as selective ER-β agonists |
-
1986
- 1986-06-13 DD DD29127686A patent/DD258820A1/en not_active IP Right Cessation
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
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US8183401B2 (en) | 2004-01-16 | 2012-05-22 | Cedarburg Pharmaceuticals, Inc. | Exemestane and its intermediates and methods of making the same |
US8541609B2 (en) | 2004-01-16 | 2013-09-24 | Cedarburg Pharmaceuticals, Inc. | Exemestane and its intermediates and methods of making the same |
EP2099460A2 (en) * | 2006-11-30 | 2009-09-16 | Endece, LLC | 6-alkoxyalkyl estradiol derivatives and methods of use |
EP2099460A4 (en) * | 2006-11-30 | 2010-03-24 | Endece Llc | 6-alkoxyalkyl estradiol derivatives and methods of use |
JP2010511625A (en) * | 2006-11-30 | 2010-04-15 | エンディース エルエルシー | 6-Alkoxyalkylestradiol derivatives and uses thereof |
AU2007325092B2 (en) * | 2006-11-30 | 2013-04-11 | Endece, Llc | 6-alkoxyalkyl estradiol derivatives and methods of use |
WO2008137048A1 (en) | 2007-05-04 | 2008-11-13 | Scinopharm Taiwan, Ltd. | Process for preparing aromatase inhibitors |
WO2011066542A2 (en) | 2009-11-30 | 2011-06-03 | Endece Inc. | 6-substituted estradiol derivatives and methods of use |
US9422324B2 (en) | 2010-09-14 | 2016-08-23 | Endece Llc | 6-substituted demethyl-estradiol derivatives as selective ER-β agonists |
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