CA2427632A1 - Process for the production of 4-(17.alpha.-substituted-3-oxoestra-4,9-dien-11.beta.-yl)benzaldehyde-(1e or 1z)-oximes - Google Patents
Process for the production of 4-(17.alpha.-substituted-3-oxoestra-4,9-dien-11.beta.-yl)benzaldehyde-(1e or 1z)-oximes Download PDFInfo
- Publication number
- CA2427632A1 CA2427632A1 CA002427632A CA2427632A CA2427632A1 CA 2427632 A1 CA2427632 A1 CA 2427632A1 CA 002427632 A CA002427632 A CA 002427632A CA 2427632 A CA2427632 A CA 2427632A CA 2427632 A1 CA2427632 A1 CA 2427632A1
- Authority
- CA
- Canada
- Prior art keywords
- beta
- alpha
- benzaldehyde
- group
- oxoestra
- 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.)
- Granted
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- 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
- C07J1/0051—Estrane derivatives
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
-
- 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
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
- C07J1/0085—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being a saturated hydrocarbon group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- 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
- C07J41/0077—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom
- C07J41/0083—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom substituted in position 11-beta by an optionally substituted phenyl group not further condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
- C07J71/0015—Oxiranes at position 9(11)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention relates to a method for the production of 4-(17.alpha. substituted 3-oxoestra-4,9-dien-11.beta.-yl)benzaldehyd-(1E or 1Z)-oximes of general formula (I), where R1 = H, C1-6 alkyl or a CnF2n+1 group; R2 = C1-4 alkyl, X = E- or Z-OH; and Y = O-C1-6 alkyl, S-C1-6 alkyl or O-CH2CnF2n+1, where n = 1, 2 or 3, which produces the target compounds of formula (I) with high yield and selectivity.
Claims (6)
1. Process for the production of 4-(17.alpha.-substituted-3-oxoestra-4,9-dien-11.beta.-yl)benzaldehyde-(1E or 1Z)-oximes of general formula (I), in which R1 means a hydrogen atom, a C1-6-alkyl radical or a CnF 2n+1 radical, R2 means a C1-4 alkyl radical, X means an OH group in E- or Z-position, and Y means an alkyl group, an SC1-6-alkyl group or an OCH2CnF2n+1 group, whereby n is 1, 2 or 3, characterized in that a 3,3-dimethoxy-5.alpha.,10.alpha.-epoxy-estr-9(11)-en-17-one of formula (II) in which R2 has the above-indicated meaning, is converted with an active methylene reagent in an inert solvent into a 5.alpha.,10.alpha.-epoxy-17(S)-spiroepoxide of formula (IX) in which R2 has the above-indicated meaning, which, after regio- and stereoselective cleavage of the 17-spiroepoxy group by alkali or alkaline-earth alcoholate, by alkylmercaptans in the presence of alkali hydroxides or potassium-tert-butanolate, by direct cleavage with alkali mercaptides or with perfluoroalkyl alcohols in the presence of alkali in an inert solvent, is opened to a 17.alpha.-substituted compound of formula (X) in which R1 represents a hydrogen atom, Y means an OC1-6-alkyl group, an SC1-6-alkyl group or an OCH2CnF2n+1 group, whereby n is 1, 2 or 3, and R2 has the above-indicated meaning, which optionally is converted by reaction of the 17.beta.-hydroxyl group with alkyl halides or haloalkyl fluorides in the presence of strong bases in an inert solvent into the 17.beta.-ethers or 17.beta.-fluoroalkyl ethers of formula (X), in which R1 is a C1-6-alkyl radical or a C n F2n+1, radical, whereby n is 1, 2 or 3, and R2 and Y have the above-indicated meanings, which is reacted with a 4-bromobenzaldehyde ketal, magnesium and Cu(I)Cl at temperatures of between -35°C and room temperature to form the corresponding 3,3-dimethoxy-5.alpha.-hydroxy-17.alpha.-CH2Y-11.beta.-benzaldehyde ketal of formula (XI) in which R1 is a hydrogen atom, a C1-6 alkyl radical or a C n F2n+1 radical, whereby n is 1, 2 or 3, R2 and Y have the above-indicated meanings, and R3 stands for a methyl radical or an ethylidene group, which is converted by acid hydrolysis of the protective groups into an 11.beta.-benzaldehyde derivative of formula (XII), in which R1, R2 and Y have the above-indicated meanings, and the aldehyde function is converted selectively by hydroxylammonium salts into a mixture of E/Z-ben-zaldoximes of general formula (I), in which X means an OH group in E- or Z-position.
2. Process according to claim 1, wherein it comprises the additional process steps to separate the mixture of the E/Z-benzaldoximes of general formula (I) by recrystallization or by chromatography into the individual components.
3. Process according to claim 1 or 2, wherein R1 means a C1-3-alkyl radical, preferably a methyl group, or a trifluoromethyl group.
4. Process according to one of claims 1 to 3, wherein R2 means a C1-3-alkyl radical, preferably a methyl group, or a trifluoromethyl group.
5. Process according to one of claims 1 to 4, wherein Y means an OC1-3-alkyl radical or an SC1-3-alkyl radical, preferably a methoxy, ethoxy, isopropyloxy, methylthio or ethylthio group, or a trifluoromethoxy group.
6. Process according to one of claims 3 to 5, wherein the compounds 4-[17.beta.-Hydroxy-17.alpha.-(methoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Hydroxy-17.alpha.-(methoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1Z-oxime, 4-[17.beta.-Methoxy-17.alpha.-(methoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Methoxy-17.alpha.-(methoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1Z-oxime, 4-[17.beta.-Ethoxy-17.alpha.-(methoxymethyl)3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Hydroxy-17.alpha.-(ethoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Methoxy-17.alpha.-(ethoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Hydroxy-17.alpha.-(isopropyloxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Methoxy-17.alpha.-(isopropyloxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime, 4-[17.beta.-Hydroxy-17.alpha.-(ethylthiomethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime and 4-{17.beta.-Hydroxy-17.alpha.-(1,1,1-trifluoroethoxymethyl)-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde-1E-oxime are produced.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10056676A DE10056676A1 (en) | 2000-11-10 | 2000-11-10 | Preparation of estradienyl-benzaldoxime derivative preparation in high yield, for use e.g. in treating endometriosis, from epoxy-estrenone by multi-stage process including selective Grignard reaction |
| DE10056676.6 | 2000-11-10 | ||
| PCT/DE2001/004218 WO2002038582A2 (en) | 2000-11-10 | 2001-11-09 | Method for the production of 4-(17alpha substituted 3-oxoestra-4,9-dien-11-yl)benzaldehyd-(1e or 1z)-oximes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2427632A1 true CA2427632A1 (en) | 2003-05-01 |
| CA2427632C CA2427632C (en) | 2010-01-26 |
Family
ID=7663441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2427632A Expired - Lifetime CA2427632C (en) | 2000-11-10 | 2001-11-09 | Process for the production of 4-(17.alpha.-substituted-3-oxoestra-4,9-dien-11.beta.-yl)benzaldehyde-(1e or 1z)-oximes |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US7214808B2 (en) |
| EP (1) | EP1339734B1 (en) |
| JP (1) | JP4263478B2 (en) |
| KR (1) | KR100836323B1 (en) |
| CN (1) | CN100368427C (en) |
| AT (1) | ATE337328T1 (en) |
| AU (2) | AU2002216911B2 (en) |
| BG (1) | BG107886A (en) |
| BR (1) | BR0115249A (en) |
| CA (1) | CA2427632C (en) |
| CZ (1) | CZ301425B6 (en) |
| DE (2) | DE10056676A1 (en) |
| EA (1) | EA005530B1 (en) |
| EE (1) | EE200300222A (en) |
| HK (1) | HK1063187A1 (en) |
| HR (1) | HRP20030458A2 (en) |
| HU (1) | HUP0301765A2 (en) |
| IL (2) | IL155680A0 (en) |
| MX (1) | MXPA03004109A (en) |
| NO (1) | NO20032080D0 (en) |
| NZ (1) | NZ525962A (en) |
| PL (1) | PL205091B1 (en) |
| SK (1) | SK286601B6 (en) |
| WO (1) | WO2002038582A2 (en) |
| YU (1) | YU34303A (en) |
| ZA (1) | ZA200304480B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102006018888A1 (en) * | 2006-04-18 | 2007-10-25 | Bayer Schering Pharma Ag | Process for the preparation of 4- [17beta-methoxy-17alpha-methoxymethyl-3-oxoestra-4,9-diene-11beta-yl] benzaldehyde (E) -oxime (asoprisnil) |
| JP4843372B2 (en) * | 2006-05-09 | 2011-12-21 | 株式会社リコー | Image processing device |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4332284C2 (en) * | 1993-09-20 | 1997-05-28 | Jenapharm Gmbh | 11-Benzaldoxime-17beta-methoxy-17alpha-methoxymethyl-estradiene derivatives, process for their preparation and medicaments containing these compounds |
| DE4332283A1 (en) * | 1993-09-20 | 1995-04-13 | Jenapharm Gmbh | Novel 11-benzaldoximestradiene derivatives, processes for their preparation and medicaments containing these compounds |
| US5576310A (en) * | 1994-09-20 | 1996-11-19 | Jenapharm Gmbh | 11-benzaldoxime-17β-methoxy-17α-methoxymethyl-estrasdiene derivatives, methods for their production and pharmaceuticals containing such compounds |
-
2000
- 2000-11-10 DE DE10056676A patent/DE10056676A1/en not_active Withdrawn
-
2001
- 2001-11-09 SK SK551-2003A patent/SK286601B6/en not_active IP Right Cessation
- 2001-11-09 WO PCT/DE2001/004218 patent/WO2002038582A2/en active IP Right Grant
- 2001-11-09 IL IL15568001A patent/IL155680A0/en unknown
- 2001-11-09 EA EA200300506A patent/EA005530B1/en not_active IP Right Cessation
- 2001-11-09 US US10/416,029 patent/US7214808B2/en not_active Expired - Lifetime
- 2001-11-09 CA CA2427632A patent/CA2427632C/en not_active Expired - Lifetime
- 2001-11-09 PL PL361399A patent/PL205091B1/en not_active IP Right Cessation
- 2001-11-09 AT AT01993608T patent/ATE337328T1/en not_active IP Right Cessation
- 2001-11-09 HU HU0301765A patent/HUP0301765A2/en unknown
- 2001-11-09 EE EEP200300222A patent/EE200300222A/en unknown
- 2001-11-09 JP JP2002541114A patent/JP4263478B2/en not_active Expired - Fee Related
- 2001-11-09 AU AU2002216911A patent/AU2002216911B2/en not_active Ceased
- 2001-11-09 YU YU34303A patent/YU34303A/en unknown
- 2001-11-09 AU AU1691102A patent/AU1691102A/en active Pending
- 2001-11-09 EP EP01993608A patent/EP1339734B1/en not_active Expired - Lifetime
- 2001-11-09 KR KR1020037006317A patent/KR100836323B1/en not_active IP Right Cessation
- 2001-11-09 NZ NZ525962A patent/NZ525962A/en unknown
- 2001-11-09 CZ CZ20031282A patent/CZ301425B6/en not_active IP Right Cessation
- 2001-11-09 MX MXPA03004109A patent/MXPA03004109A/en active IP Right Grant
- 2001-11-09 DE DE50110829T patent/DE50110829D1/en not_active Expired - Lifetime
- 2001-11-09 BR BR0115249-1A patent/BR0115249A/en not_active IP Right Cessation
- 2001-11-09 CN CNB018186785A patent/CN100368427C/en not_active Expired - Fee Related
-
2003
- 2003-04-30 IL IL155680A patent/IL155680A/en not_active IP Right Cessation
- 2003-05-09 NO NO20032080A patent/NO20032080D0/en unknown
- 2003-06-06 BG BG107886A patent/BG107886A/en unknown
- 2003-06-06 HR HR20030458A patent/HRP20030458A2/en not_active Application Discontinuation
- 2003-06-09 ZA ZA200304480A patent/ZA200304480B/en unknown
-
2004
- 2004-08-10 HK HK04105980A patent/HK1063187A1/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |