CA2839228A1 - Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil) - Google Patents

Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil) Download PDF

Info

Publication number: CA2839228A1
Authority: CA; Canada
Prior art keywords: asoprisnil; microparticles according; asoprisnil microparticles; beta; hydroxyestradienone
Prior art date: 2006-04-18
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.): Abandoned

Application number

CA2839228A

Other languages

English (en)

Inventor

Detlef Grawe

Sabine Gliesing

Hagen Gerecke

Peter Hoesel

Uwe Mueller

Thomas Michel

Robert Eilers

Uwe Knabe

Bernd Erhart

Michael Mosebach

David Voigtlaender

Ulf Tilstam

Juergen Jacke

Klaus Bahl

Ulf Bohlmann

Dieter Wehmeier

Michael Sander

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Intellectual Property GmbH

Original Assignee

Bayer Intellectual Property GmbH

Priority date (The priority date 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 date listed.)

2006-04-18

Filing date

2007-04-17

Publication date

2007-10-25

2007-04-17 Application filed by Bayer Intellectual Property GmbH filed Critical Bayer Intellectual Property GmbH

2007-10-25 Publication of CA2839228A1 publication Critical patent/CA2839228A1/fr

Status Abandoned legal-status Critical Current

Links

GJMNAFGEUJBOCE-MEQIQULJSA-N asoprisnil Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@]([C@]3(C2)C)(COC)OC)=CC=C(\C=N\O)C=C1 GJMNAFGEUJBOCE-MEQIQULJSA-N 0.000 title claims abstract description 90
229950003620 asoprisnil Drugs 0.000 title claims abstract description 90
238000000034 method Methods 0.000 title claims abstract description 58
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 title abstract description 8
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 title abstract description 4
239000007787 solid Substances 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 99
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 51
238000006243 chemical reaction Methods 0.000 claims description 50
239000011859 microparticle Substances 0.000 claims description 46
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 38
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
MLMJCNNPMGMWII-FOSLCNLBSA-N (9r,10s,13s)-13-(hydroxymethyl)-2,3,4,5,6,7,9,10,11,12-decahydro-1h-cyclopenta[a]phenanthren-17-one Chemical compound C([C@@H]1[C@H]2CC3)CCCC1CCC2=C1[C@@]3(CO)C(=O)C=C1 MLMJCNNPMGMWII-FOSLCNLBSA-N 0.000 claims description 28
239000000047 product Substances 0.000 claims description 27
238000001035 drying Methods 0.000 claims description 26
239000012071 phase Substances 0.000 claims description 22
239000002245 particle Substances 0.000 claims description 19
150000001299 aldehydes Chemical class 0.000 claims description 18
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 16
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 claims description 16
238000005907 ketalization reaction Methods 0.000 claims description 15
230000003647 oxidation Effects 0.000 claims description 15
238000007254 oxidation reaction Methods 0.000 claims description 15
-1 dimethoxy acetal Chemical class 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
238000001694 spray drying Methods 0.000 claims description 13
150000003431 steroids Chemical class 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
150000002500 ions Chemical class 0.000 claims description 9
238000000746 purification Methods 0.000 claims description 9
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 8
238000001816 cooling Methods 0.000 claims description 8
238000010438 heat treatment Methods 0.000 claims description 8
RXYLXDKWPRPXMI-UHFFFAOYSA-N 1-bromo-2-(dimethoxymethyl)benzene Chemical compound COC(OC)C1=CC=CC=C1Br RXYLXDKWPRPXMI-UHFFFAOYSA-N 0.000 claims description 5
238000003747 Grignard reaction Methods 0.000 claims description 5
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 5
230000002378 acidificating effect Effects 0.000 claims description 5
230000004927 fusion Effects 0.000 claims description 5
238000005507 spraying Methods 0.000 claims description 5
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
238000010533 azeotropic distillation Methods 0.000 claims description 4
238000004587 chromatography analysis Methods 0.000 claims description 4
239000012530 fluid Substances 0.000 claims description 4
238000011010 flushing procedure Methods 0.000 claims description 4
238000009736 wetting Methods 0.000 claims description 4
239000007795 chemical reaction product Substances 0.000 claims description 3
230000008021 deposition Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
239000007921 spray Substances 0.000 claims description 3
230000009885 systemic effect Effects 0.000 claims description 3
BHTWZQKERRCPRZ-RYRKJORJSA-N Estra-4,9-diene-3,17-dione Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)(C(CC3)=O)CC3)C3=C21 BHTWZQKERRCPRZ-RYRKJORJSA-N 0.000 claims description 2
239000002841 Lewis acid Substances 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
238000011109 contamination Methods 0.000 claims description 2
SDZRMTOYMKCDIO-UHFFFAOYSA-M di(propan-2-yloxy)alumanyl 2,2,2-trifluoroacetate Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].[O-]C(=O)C(F)(F)F SDZRMTOYMKCDIO-UHFFFAOYSA-M 0.000 claims description 2
150000007517 lewis acids Chemical class 0.000 claims description 2
239000007791 liquid phase Substances 0.000 claims description 2
239000000376 reactant Substances 0.000 claims description 2
230000002194 synthesizing effect Effects 0.000 claims 5
238000006036 Oppenauer oxidation reaction Methods 0.000 claims 3
239000003814 drug Substances 0.000 claims 3
PUQSDJZESAQGQS-OWSLCNJRSA-N (8s,13s,14s,17s)-17-hydroxy-13-methyl-2,6,7,8,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@H](CC3)O)CC3)C3=C21 PUQSDJZESAQGQS-OWSLCNJRSA-N 0.000 claims 2
201000009273 Endometriosis Diseases 0.000 claims 1
206010046798 Uterine leiomyoma Diseases 0.000 claims 1
238000006555 catalytic reaction Methods 0.000 claims 1
230000001419 dependent effect Effects 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
230000004064 dysfunction Effects 0.000 claims 1
230000035558 fertility Effects 0.000 claims 1
229940088597 hormone Drugs 0.000 claims 1
239000005556 hormone Substances 0.000 claims 1
238000002657 hormone replacement therapy Methods 0.000 claims 1
201000010260 leiomyoma Diseases 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 28
239000012074 organic phase Substances 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
239000004480 active ingredient Substances 0.000 description 17
239000000203 mixture Substances 0.000 description 17
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
238000004821 distillation Methods 0.000 description 12
238000003756 stirring Methods 0.000 description 11
239000001117 sulphuric acid Substances 0.000 description 11
235000011149 sulphuric acid Nutrition 0.000 description 11
238000002425 crystallisation Methods 0.000 description 10
230000008025 crystallization Effects 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
239000000126 substance Substances 0.000 description 10
238000003786 synthesis reaction Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000007789 gas Substances 0.000 description 9
239000006227 byproduct Substances 0.000 description 8
239000012043 crude product Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
238000009826 distribution Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
230000008859 change Effects 0.000 description 4
239000012535 impurity Substances 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
229940117975 chromium trioxide Drugs 0.000 description 3
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 3
238000000113 differential scanning calorimetry Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
YEOAIJNHLPFTRM-AOIWGVFYSA-N (8s,13s,14s)-3,3-dimethoxy-13-methyl-1,2,4,6,7,8,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-one Chemical compound C1C=C2C(CCC(C3)(OC)OC)=C3CC[C@H]2[C@@H]2CCC(=O)[C@]21C YEOAIJNHLPFTRM-AOIWGVFYSA-N 0.000 description 2
VXEGSRKPIUDPQT-UHFFFAOYSA-N 4-[4-(4-methoxyphenyl)piperazin-1-yl]aniline Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2C=CC(N)=CC=2)CC1 VXEGSRKPIUDPQT-UHFFFAOYSA-N 0.000 description 2
ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000004133 Sodium thiosulphate Substances 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
238000006359 acetalization reaction Methods 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
239000004411 aluminium Substances 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
230000008901 benefit Effects 0.000 description 2
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
AZFLJNIPTRTECV-FUMNGEBKSA-N dienogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC#N)CC3)C3=C21 AZFLJNIPTRTECV-FUMNGEBKSA-N 0.000 description 2
229960003309 dienogest Drugs 0.000 description 2
229940088679 drug related substance Drugs 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000012467 final product Substances 0.000 description 2
150000004795 grignard reagents Chemical class 0.000 description 2
VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000000463 material Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
238000010899 nucleation Methods 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000000634 powder X-ray diffraction Methods 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000005049 silicon tetrachloride Substances 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000012546 transfer Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 2
NNWBVVMIBVKXKR-YAUBAPCASA-N (1R,5S,9S,10S,13R)-15,15-dimethoxy-5-methyl-18-oxapentacyclo[11.4.1.01,13.02,10.05,9]octadec-2-en-6-one Chemical compound C([C@]1(C)C(=O)CC[C@H]1[C@@H]1CC2)C=C1[C@]13CCC(OC)(OC)C[C@@]12O3 NNWBVVMIBVKXKR-YAUBAPCASA-N 0.000 description 1
NULYJUJAALNWOJ-GAZPGATBSA-N (7r,8r,13s,14s)-7-(methoxymethyl)-13-methyl-2,6,7,8,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C[C@]2(C)CCC[C@H]2[C@@H]2[C@H](COC)CC3=CC(=O)CCC3=C21 NULYJUJAALNWOJ-GAZPGATBSA-N 0.000 description 1
APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
TWFNGPDYMFEHOB-UHFFFAOYSA-N 1-bromo-4-(dimethoxymethyl)benzene Chemical compound COC(OC)C1=CC=C(Br)C=C1 TWFNGPDYMFEHOB-UHFFFAOYSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical group CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000000889 atomisation Methods 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000003889 chemical engineering Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
150000001844 chromium Chemical class 0.000 description 1
229910052804 chromium Inorganic materials 0.000 description 1
239000011651 chromium Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000010949 copper Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000001934 delay Effects 0.000 description 1
230000001687 destabilization Effects 0.000 description 1
150000001993 dienes Chemical class 0.000 description 1
238000002050 diffraction method Methods 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
125000005594 diketone group Chemical group 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
238000006735 epoxidation reaction Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
238000011005 laboratory method Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
239000004810 polytetrafluoroethylene Substances 0.000 description 1
229920001343 polytetrafluoroethylene Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000010349 pulsation Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
239000010802 sludge Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000004753 textile Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/36—Antigestagens
- 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
- 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
- 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
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- 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

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Reproductive Health (AREA)
Epidemiology (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Medicinal Preparation (AREA)

CA2839228A 2006-04-18 2007-04-17 Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil) Abandoned CA2839228A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE102006018888.8		2006-04-18
DE102006018888A DE102006018888A1 (de)	2006-04-18	2006-04-18	Verfahren zur Herstellung von 4-[17beta-Methoxy-17alpha-methoxymethyl-3-oxoestra-4,9-dien-11beta-yl]benzaldehyd-(E)-oxims (Asoprisnil)
CA2648537A CA2648537C (fr)	2006-04-18	2007-04-17	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2648537A Division CA2648537C (fr)	2006-04-18	2007-04-17	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)

Publications (1)

Publication Number	Publication Date
CA2839228A1 true CA2839228A1 (fr)	2007-10-25

Family

ID=38536818

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA2839228A Abandoned CA2839228A1 (fr)	2006-04-18	2007-04-17	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)
CA2648537A Active CA2648537C (fr)	2006-04-18	2007-04-17	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA2648537A Active CA2648537C (fr)	2006-04-18	2007-04-17	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)

Country Status (12)

Country	Link
EP (1)	EP2010555A2 (fr)
JP (1)	JP2009534345A (fr)
KR (1)	KR20080110629A (fr)
CN (1)	CN101466724A (fr)
AU (1)	AU2007237457A1 (fr)
BR (1)	BRPI0710517A2 (fr)
CA (2)	CA2839228A1 (fr)
DE (1)	DE102006018888A1 (fr)
MX (2)	MX2007000450A (fr)
RU (1)	RU2008145098A (fr)
WO (1)	WO2007118717A2 (fr)
ZA (1)	ZA200809787B (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN108003210A (zh) *	2018-01-24	2018-05-08	四川理工学院	一种雌甾-4,9-二烯-3,17-二酮的制备方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR5183M (fr) *	1966-03-04	1967-06-19
ZA8231B (en) *	1981-01-09	1982-11-24	Roussel Uclaf	New 11 -substituted steroid derivatives, their preparation, their use as medicaments, the compositions containing them and the new intermediates thus obtained
DD296931A5 (de) *	1987-08-28	1991-12-19	Jenapharm Gmbh Jena,De	Verfahren zur herstellung von 13 beta-alkyl-5(10),9(11)-gonadienderivaten
US4910191A (en) *	1988-06-28	1990-03-20	Merrell Dow Pharmaceuticals Inc.	19-substituted progesterone derivatives useful as 19-hydroxylase inhibitors
DE4332283A1 (de) *	1993-09-20	1995-04-13	Jenapharm Gmbh	Neue 11-Benzaldoximestradien-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
EP1157996A1 (fr) *	2000-05-23	2001-11-28	JENAPHARM GmbH	Nouveaux formes solides du mesoprogestin 11beta-(4E-(hxdroxyiminomethyl)-phenyl)-17alpha-methoxymethyl-17beta-methoxy-estra-4,9-dien-3-on
DE10056675A1 (de) *	2000-11-10	2002-05-16	Jenapharm Gmbh	Verfahren zur Herstellung von 4-(17alpha-Methylsubstituierten 3-Oxoestra-4,9-dien-11ß-yl)-benzaldehyd-(1E oder 1Z)-oximen
DE10056676A1 (de) *	2000-11-10	2002-05-16	Jenapharm Gmbh	Verfahren zur Herstellung von 4-/17alpha-substituierten-3-oxoestra-4,9-dien-11beta-yl)benzaldehyd-(1E oder 1Z)-oximen
JP4197890B2 (ja) *	2001-05-24	2008-12-17	興和創薬株式会社	第一級アリルアルコール類の酸化方法
DE10311092A1 (de) *	2003-03-07	2004-10-07	Schering Ag	Verfahren zur Oxidation der 17-Hydroxylfunktion in Steroiden und die Verwendung von Trifluoressigsäure und Cyclohexanon zur Herstellung von steroidalen 17-Ketonen mittels Oppenauer Oxidation
DE102004021060A1 (de) *	2004-04-29	2005-11-24	Schering Ag	Wiederfindung von Arzneistoffen im ppm-Bereich in Produktionsanlagen

2006
- 2006-04-18 DE DE102006018888A patent/DE102006018888A1/de not_active Ceased
2007
- 2007-01-12 MX MX2007000450A patent/MX2007000450A/es not_active Application Discontinuation
- 2007-04-17 BR BRPI0710517-7A patent/BRPI0710517A2/pt not_active IP Right Cessation
- 2007-04-17 AU AU2007237457A patent/AU2007237457A1/en not_active Abandoned
- 2007-04-17 CA CA2839228A patent/CA2839228A1/fr not_active Abandoned
- 2007-04-17 CA CA2648537A patent/CA2648537C/fr active Active
- 2007-04-17 JP JP2009505800A patent/JP2009534345A/ja active Pending
- 2007-04-17 KR KR1020087025453A patent/KR20080110629A/ko not_active Withdrawn
- 2007-04-17 MX MX2008013336A patent/MX2008013336A/es unknown
- 2007-04-17 EP EP07724653A patent/EP2010555A2/fr not_active Withdrawn
- 2007-04-17 RU RU2008145098/04A patent/RU2008145098A/ru not_active Application Discontinuation
- 2007-04-17 CN CNA2007800212624A patent/CN101466724A/zh active Pending
- 2007-04-17 WO PCT/EP2007/003723 patent/WO2007118717A2/fr not_active Ceased
2008
- 2008-11-17 ZA ZA200809787A patent/ZA200809787B/xx unknown

Also Published As

Publication number	Publication date
CN101466724A (zh)	2009-06-24
EP2010555A2 (fr)	2009-01-07
WO2007118717A2 (fr)	2007-10-25
ZA200809787B (en)	2010-01-27
KR20080110629A (ko)	2008-12-18
WO2007118717A3 (fr)	2008-04-24
BRPI0710517A2 (pt)	2011-08-16
RU2008145098A (ru)	2010-05-27
DE102006018888A1 (de)	2007-10-25
AU2007237457A1 (en)	2007-10-25
MX2008013336A (es)	2008-10-31
CA2648537C (fr)	2014-09-23
CA2648537A1 (fr)	2007-10-25
JP2009534345A (ja)	2009-09-24
MX2007000450A (es)	2009-02-11

Legal Events

Date	Code	Title	Description
2014-02-06	EEER	Examination request	Effective date: 20140114
2017-04-25	FZDE	Discontinued	Effective date: 20170314

Publication	Publication Date	Title
JP3977462B2 (ja)	2007-09-19	１１−（置換フェニル）−エストラ−４，９−ジエン誘導体
US6072068A (en)	2000-06-06	16-hydroxy-11-(substituted phenyl)-estra-4,9-diene derivatives
JPH09309897A (ja)	1997-12-02	コレステロール低下剤およびアテローム硬化症抑制剤を製造するためのステロイドグリコシドの使用
US11633406B2 (en)	2023-04-25	Industrial process for the preparation of high purity estetrol
SK135195A3 (en)	1996-03-06	Crystaline spirostalnylglycosidal, its monohydrate pharmaceutical agent on its base and method of production of crystaline steroid glycoside
EP1862469A2 (fr)	2007-12-05	Formes de corps solide nouvelles du mesoprogestine 11bêta-[4E-(hydroxyiminomethyl)-phényle]-17alpha-methoxyméthyle-17bêta-methoxy-estra-4,9-dien-3-on
CA2648537C (fr)	2014-09-23	Methode de preparation de 4-[17.beta.-methoxy-17.alpha.-methoxymethyl-3-oxoestra-4,9-dien-11.beta.-yl]benzaldehyde (e)-oxime (asoprisnil)
AU2006323005B2 (en)	2013-05-30	High purity 17alpha-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one and process for the synthesis thereof
US8324412B2 (en)	2012-12-04	Method for preparing 4-[17β-methoxy-17α-methoxymethyl-3-oxoestra-4,9-dien-11β-yl]benzaldehyde (E)-oxime (asoprisnil)
HK1131993A (en)	2010-02-12	METHOD FOR PREPARING 4-[17β-METHOXY-17α-METHOXYMETHYL-3-OXOESTRA-4,9-DIEN-11β-YL]BENZALDEHYDE (E)-OXIME (ASOPRISNIL)
RU2802820C2 (ru)	2023-09-04	Промышленный способ получения высокочистого эстетрола
JP2834721B2 (ja)	1998-12-14	１７α−シアノメチルエストラ−４，９−ジエン誘導体、その製造方法および該化合物を含有する医薬品
EP4000688A1 (fr)	2022-05-25	Procédé pour la préparation d'acétate trenbolone ayant une distribution granulométrique définie
EA042770B1 (ru)	2023-03-23	Промышленный способ получения высокочистого эстетрола
BR112022003254B1 (pt)	2023-06-13	Processo para a preparação de estetrol, e, compostos das fórmulas gerais (iii) e (iv)
ZA200506943B (en)	2006-07-26	Process for preparing cryalline ciclesonide with defined particle size
HK1002010B (en)	2000-04-07	11-(substituted phenyl)-estra-4, 9-diene derivatives
HU186687B (en)	1985-09-30	Process for preparing 11beta-chloro-steroids and pharmaceutical compositions containing such compounds