ZA200507281B - Process for the production of tibolone - Google Patents
Process for the production of tibolone Download PDFInfo
- Publication number
- ZA200507281B ZA200507281B ZA200507281A ZA200507281A ZA200507281B ZA 200507281 B ZA200507281 B ZA 200507281B ZA 200507281 A ZA200507281 A ZA 200507281A ZA 200507281 A ZA200507281 A ZA 200507281A ZA 200507281 B ZA200507281 B ZA 200507281B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- process according
- compound
- carried out
- produce
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 121
- WZDGZWOAQTVYBX-XOINTXKNSA-N tibolone Chemical compound C([C@@H]12)C[C@]3(C)[C@@](C#C)(O)CC[C@H]3[C@@H]1[C@H](C)CC1=C2CCC(=O)C1 WZDGZWOAQTVYBX-XOINTXKNSA-N 0.000 title claims description 27
- 229960001023 tibolone Drugs 0.000 title claims description 25
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
- 239000010949 copper Substances 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910052802 copper Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- 229960004719 nandrolone Drugs 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 230000002140 halogenating effect Effects 0.000 claims description 7
- -1 methyl-magnesium halide Chemical class 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 230000001035 methylating effect Effects 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 150000002576 ketones Chemical group 0.000 claims description 3
- 239000012345 acetylating agent Substances 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 6
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 229960000443 hydrochloric acid Drugs 0.000 claims 3
- 235000011167 hydrochloric acid Nutrition 0.000 claims 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 150000004703 alkoxides Chemical class 0.000 claims 2
- 239000004411 aluminium Substances 0.000 claims 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 2
- 229910052782 aluminium Inorganic materials 0.000 claims 2
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- 235000006708 antioxidants Nutrition 0.000 claims 2
- 239000011575 calcium Substances 0.000 claims 2
- SFDZETWZUCDYMD-UHFFFAOYSA-N monosodium acetylide Chemical compound [Na+].[C-]#C SFDZETWZUCDYMD-UHFFFAOYSA-N 0.000 claims 2
- 238000005580 one pot reaction Methods 0.000 claims 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims 1
- 101100381997 Danio rerio tbc1d32 gene Proteins 0.000 claims 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 claims 1
- 101100381999 Mus musculus Tbc1d32 gene Proteins 0.000 claims 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- 241001208007 Procas Species 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 229960005070 ascorbic acid Drugs 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 claims 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims 1
- 229910052808 lithium carbonate Inorganic materials 0.000 claims 1
- GWGVDNZFTPIGDY-UHFFFAOYSA-M magnesium;ethyne;chloride Chemical compound [Mg+2].[Cl-].[C-]#C GWGVDNZFTPIGDY-UHFFFAOYSA-M 0.000 claims 1
- 229910017604 nitric acid Inorganic materials 0.000 claims 1
- 238000001953 recrystallisation Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 239000000047 product Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 238000007069 methylation reaction Methods 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CIHXIRAAMAUYLZ-UHFFFAOYSA-N [K+].[K+].[C-]#[C-] Chemical compound [K+].[K+].[C-]#[C-] CIHXIRAAMAUYLZ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 239000012374 esterification agent Substances 0.000 description 2
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 2
- 239000012022 methylating agents Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- CZVLELWCMFBHBN-YRXWBPOGSA-N (8s,9s,13s,14s)-3-methoxy-13-methyl-1,4,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene Chemical compound C1C[C@@H]2C(CC=C(C3)OC)=C3CC[C@H]2[C@@H]2CCC[C@]21C CZVLELWCMFBHBN-YRXWBPOGSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- 238000006027 Birch reduction reaction Methods 0.000 description 1
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010027304 Menopausal symptoms Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 150000001844 chromium Chemical class 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 238000012777 commercial manufacturing Methods 0.000 description 1
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000757 progestagenic effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0304927.7A GB0304927D0 (en) | 2003-03-04 | 2003-03-04 | Process for the production of tibolone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200507281B true ZA200507281B (en) | 2006-12-27 |
Family
ID=9954086
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200507281A ZA200507281B (en) | 2003-03-04 | 2004-03-03 | Process for the production of tibolone |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7884222B2 (zh) |
| EP (2) | EP1608670B1 (zh) |
| JP (1) | JP2006519248A (zh) |
| CN (1) | CN100420699C (zh) |
| AU (1) | AU2004218221C1 (zh) |
| BR (1) | BRPI0408104A (zh) |
| CA (1) | CA2517934A1 (zh) |
| GB (1) | GB0304927D0 (zh) |
| NO (1) | NO20054111L (zh) |
| NZ (1) | NZ542298A (zh) |
| WO (1) | WO2004078774A1 (zh) |
| ZA (1) | ZA200507281B (zh) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2070942A1 (de) * | 2007-12-13 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Verfahren zur Aromatisierung von 19-Nor-androst-4-en-3-onen zu Estra-1,3,5(10)-trienen |
| BRPI1012669A2 (pt) * | 2009-06-29 | 2016-04-05 | Merz Pharma Gmbh & Co Kgaa | metodo de preparacao de 3,3,5,5-tetrametliciclohexanona, método de preparção de 1-amino-1,3,3,5,5,-pentametilciclohexano ou um sal farmaceuticamente aceitável do mesmo e composto |
| EP2675820A1 (en) * | 2011-02-17 | 2013-12-25 | Lupin Limited | An improved process for preparation of levonorgestrel |
| CN104292285A (zh) * | 2014-09-30 | 2015-01-21 | 湖北三晶生物科技有限公司 | 一种高含量脱氢诺龙醋酸酯的合成工艺 |
| CN107365340A (zh) * | 2017-07-05 | 2017-11-21 | 湖北工业大学 | 一种3,5‑雌甾二烯‑3,17β‑二醋酸酯的制备方法 |
| CN107200762A (zh) * | 2017-07-12 | 2017-09-26 | 湖北共同生物科技有限公司 | 3,5‑雌甾二烯‑3,17β‑二醋酸酯的制备方法 |
| CN109575094B (zh) * | 2019-01-17 | 2021-01-26 | 浙江仙琚制药股份有限公司 | 替勃龙中间体的制备方法 |
| CN110981930B (zh) * | 2019-12-31 | 2021-04-20 | 浙江仙居君业药业有限公司 | 一种替勃龙的合成方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2798879A (en) * | 1953-04-15 | 1957-07-09 | Upjohn Co | 19-nortestosterone acylates and 3-enol acylates thereof |
| US2957933A (en) * | 1957-06-08 | 1960-10-25 | Basf Ag | Production of compounds of the betacyclo-geranylidene series |
| US3341557A (en) * | 1961-06-05 | 1967-09-12 | Upjohn Co | 7-methyltestosterones |
| BE665514A (zh) * | 1964-06-16 | |||
| CH488682A (de) * | 1965-07-30 | 1970-04-15 | Ciba Geigy | Verfahren zur Herstellung von 4,9,11-Trienen der 19-Nor-androstanreihe |
| NL146838B (nl) * | 1966-06-24 | 1975-08-15 | Organon Nv | Werkwijze voor het bereiden van (delta)5(10)-3- keto-19-norsteroiden. |
| US3515719A (en) * | 1967-03-15 | 1970-06-02 | Upjohn Co | 7-methyl-6,19-epoxy steroids of the androstane series |
| CH547268A (de) * | 1968-10-25 | 1974-03-29 | Merck Patent Gmbh | Verfahren zur herstellung von n-disubstituierten 3-amino3,5-dien-19-nor-steroiden. |
| AU1005270A (en) * | 1969-01-16 | 1971-07-08 | F. Hoffmann-Laroche & Co. Aktiengesellschaft | 19 homo steroids |
| US4000273A (en) * | 1973-11-01 | 1976-12-28 | Richardson-Merrell Inc. | Method for the control of fertility |
| FR2311030A1 (fr) | 1975-05-16 | 1976-12-10 | Aries Robert | Esters vinyliques d'hormones sexuelles |
| NL7510104A (nl) * | 1975-08-27 | 1977-03-01 | Akzo Nv | Werkwijze ter bereiding van een oraal werkzaam farmaceutisch preparaat. |
| GB1527161A (en) | 1976-02-19 | 1978-10-04 | Leo A | Enol esters of steroids |
| JPS5655400A (en) * | 1979-10-12 | 1981-05-15 | Mitsubishi Chem Ind Ltd | Improved preparation process of 4,6-dien-3-one steroid |
| DE3612632A1 (de) * | 1986-04-11 | 1987-10-22 | Schering Ag | Verfahren zur herstellung von 7(alpha)-propylsteroiden |
| DK24089D0 (da) | 1989-01-20 | 1989-01-20 | Hans Bundgaard | Novel prodrug derivatives of biologically active agents containing hydroxyl groups or nh-acidic groups |
| IE63051B1 (en) | 1989-03-18 | 1995-03-22 | Akzo Nv | Pharmaceutical composition which contains a pharmaceutically suitable carrier and the compound having the structure (7alpha, 17alpha)-17-Hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn- 3-one |
| CA2425849C (en) | 1991-11-22 | 2007-02-27 | Alcon Laboratories, Inc. | Angiostatic steroids |
| JP2746041B2 (ja) | 1992-02-14 | 1998-04-28 | 三菱化学株式会社 | 新規なステロイド誘導体 |
| DE4308095A1 (de) | 1993-03-13 | 1994-09-15 | Hoechst Ag | Prodrug-Derivate von Arzneimittelwirkstoffen mit Hydroxylgruppen, Verfahren zu deren Herstellung und ihre Verwendung |
| GB2321455A (en) | 1997-01-24 | 1998-07-29 | Norsk Hydro As | Lipophilic derivatives of biologically active compounds |
| WO1999067270A1 (en) | 1998-06-19 | 1999-12-29 | Akzo Nobel N.V. | Cycloalkyl-carboxylic acid esters of 7.alpha.methyl-estr-4-en-3-one 17.beta.-ol (19-nor 7.alpha.-methyltestosterone) |
| CN1172949C (zh) | 1998-06-19 | 2004-10-27 | 阿克佐诺贝尔公司 | 睾酮衍生物 |
| TW577893B (en) | 1998-10-16 | 2004-03-01 | Akzo Nobel Nv | High purity composition comprising (7alpha, 17alpha)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one |
| PT1163256E (pt) | 1999-03-23 | 2004-07-30 | Hollis Eden Pharmaceuticals | Hemi-hidrato de 16-alfa-bromoepiandrosterona |
| AU5209600A (en) | 1999-04-06 | 2000-10-23 | Akzo Nobel N.V. | Orally active androgens |
| WO2000066613A1 (en) | 1999-04-30 | 2000-11-09 | Research Corporation Technologies, Inc. | Bone targeting agents for osteoporosis |
| EP1189922A4 (en) | 1999-04-30 | 2002-08-14 | Arch Dev Corp | STEROID DERIVATIVES |
| TW548277B (en) * | 1999-07-16 | 2003-08-21 | Akzo Nobel Nv | Orally active androgens |
| AUPQ342599A0 (en) | 1999-10-14 | 1999-11-04 | University Of Melbourne, The | Conjugates and uses thereof |
| TWI322813B (en) * | 2002-01-21 | 2010-04-01 | Organon Nv | Process for the preparation of 7alpha-methylsteroids |
-
2003
- 2003-03-04 GB GBGB0304927.7A patent/GB0304927D0/en not_active Ceased
-
2004
- 2004-03-03 BR BRPI0408104-8A patent/BRPI0408104A/pt active Search and Examination
- 2004-03-03 AU AU2004218221A patent/AU2004218221C1/en not_active Ceased
- 2004-03-03 CN CNB2004800112393A patent/CN100420699C/zh not_active Expired - Fee Related
- 2004-03-03 EP EP04716642.6A patent/EP1608670B1/en not_active Expired - Lifetime
- 2004-03-03 NZ NZ542298A patent/NZ542298A/en not_active IP Right Cessation
- 2004-03-03 WO PCT/GB2004/000887 patent/WO2004078774A1/en active Application Filing
- 2004-03-03 CA CA002517934A patent/CA2517934A1/en not_active Abandoned
- 2004-03-03 EP EP10186130A patent/EP2497776A3/en not_active Withdrawn
- 2004-03-03 US US10/548,114 patent/US7884222B2/en not_active Expired - Fee Related
- 2004-03-03 ZA ZA200507281A patent/ZA200507281B/en unknown
- 2004-03-03 JP JP2006505910A patent/JP2006519248A/ja active Pending
-
2005
- 2005-09-05 NO NO20054111A patent/NO20054111L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20054111D0 (no) | 2005-09-05 |
| AU2004218221A1 (en) | 2004-09-16 |
| EP2497776A2 (en) | 2012-09-12 |
| JP2006519248A (ja) | 2006-08-24 |
| AU2004218221C1 (en) | 2011-07-07 |
| GB0304927D0 (en) | 2003-04-09 |
| EP2497776A3 (en) | 2013-01-02 |
| CN100420699C (zh) | 2008-09-24 |
| BRPI0408104A (pt) | 2006-03-01 |
| NO20054111L (no) | 2005-12-02 |
| AU2004218221B2 (en) | 2010-11-11 |
| CN1780849A (zh) | 2006-05-31 |
| US7884222B2 (en) | 2011-02-08 |
| EP1608670A1 (en) | 2005-12-28 |
| NZ542298A (en) | 2008-07-31 |
| CA2517934A1 (en) | 2004-09-16 |
| WO2004078774A1 (en) | 2004-09-16 |
| EP1608670B1 (en) | 2013-09-11 |
| US20060173201A1 (en) | 2006-08-03 |
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