NO327095B1 - Fremgangsmate for fremstilling av 7alfa-metylsteroider - Google Patents
Fremgangsmate for fremstilling av 7alfa-metylsteroider Download PDFInfo
- Publication number
- NO327095B1 NO327095B1 NO20043455A NO20043455A NO327095B1 NO 327095 B1 NO327095 B1 NO 327095B1 NO 20043455 A NO20043455 A NO 20043455A NO 20043455 A NO20043455 A NO 20043455A NO 327095 B1 NO327095 B1 NO 327095B1
- Authority
- NO
- Norway
- Prior art keywords
- hydroxy
- methyl
- copper
- steroid
- mmol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 34
- 230000008569 process Effects 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 36
- 150000003431 steroids Chemical class 0.000 claims description 22
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 239000007818 Grignard reagent Substances 0.000 claims description 10
- 150000004795 grignard reagents Chemical class 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 239000010949 copper Substances 0.000 claims description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 6
- 238000003747 Grignard reaction Methods 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 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 description 8
- YSGQGNQWBLYHPE-CFUSNLFHSA-N (7r,8r,9s,10r,13s,14s,17s)-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](C)CC3=CC(=O)CC[C@@H]3[C@H]21 YSGQGNQWBLYHPE-CFUSNLFHSA-N 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- -1 triene citrate Chemical class 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229960001023 tibolone Drugs 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000002159 estradiols Chemical class 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- ZHTDDOWJIRXOMA-HDFQMZGSSA-N (8r,9s,13s,14s)-3,17-dihydroxy-13-methyl-8,9,11,12,14,15,16,17-octahydro-7h-cyclopenta[a]phenanthren-6-one Chemical class OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)O)[C@@H]4[C@@H]3CC(=O)C2=C1 ZHTDDOWJIRXOMA-HDFQMZGSSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000007259 addition reaction Methods 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000001076 estrogenic effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000002657 hormone replacement therapy Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- ZHTDDOWJIRXOMA-YVEZLPLXSA-N (8r,9s,13s,14s,17s)-3,17-dihydroxy-13-methyl-8,9,11,12,14,15,16,17-octahydro-7h-cyclopenta[a]phenanthren-6-one Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC(=O)C2=C1 ZHTDDOWJIRXOMA-YVEZLPLXSA-N 0.000 description 1
- YSGQGNQWBLYHPE-UHFFFAOYSA-N 17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2(C)C(O)CCC2C2C(C)CC3=CC(=O)CCC3C21 YSGQGNQWBLYHPE-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 238000006960 Hosomi-Sakurai reaction Methods 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
- 206010067572 Oestrogenic effect Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960004719 nandrolone Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010915 one-step procedure Methods 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 230000001331 thermoregulatory effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
Classifications
-
- 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
- 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
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- 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
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0096—Alkynyl derivatives
-
- 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
-
- 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
- C07J5/0007—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 not substituted in position 17 alfa
- C07J5/0015—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 not substituted in position 17 alfa not substituted in position 16
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02075230 | 2002-01-21 | ||
| PCT/EP2003/000339 WO2003059931A1 (en) | 2002-01-21 | 2003-01-14 | PROCESS FOR THE PREPARATION OF 7α-METHYLSTEROIDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20043455L NO20043455L (no) | 2004-08-19 |
| NO327095B1 true NO327095B1 (no) | 2009-04-20 |
Family
ID=8185555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20043455A NO327095B1 (no) | 2002-01-21 | 2004-08-19 | Fremgangsmate for fremstilling av 7alfa-metylsteroider |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US20050090476A1 (is) |
| EP (1) | EP1470151B1 (is) |
| JP (1) | JP5250174B2 (is) |
| KR (1) | KR100937179B1 (is) |
| CN (1) | CN100372864C (is) |
| AR (1) | AR038165A1 (is) |
| AT (1) | ATE453659T1 (is) |
| AU (1) | AU2003205604B8 (is) |
| BR (1) | BRPI0306736B8 (is) |
| CA (1) | CA2472379C (is) |
| DE (1) | DE60330749D1 (is) |
| EC (1) | ECSP045180A (is) |
| EG (1) | EG23417A (is) |
| ES (1) | ES2336439T3 (is) |
| HR (1) | HRP20040634B1 (is) |
| IL (2) | IL162770A0 (is) |
| IS (1) | IS2740B (is) |
| MX (1) | MXPA04007049A (is) |
| NO (1) | NO327095B1 (is) |
| NZ (1) | NZ533970A (is) |
| PE (1) | PE20030926A1 (is) |
| PL (1) | PL208163B1 (is) |
| RO (1) | RO122913B1 (is) |
| RS (1) | RS51490B (is) |
| RU (1) | RU2305105C2 (is) |
| TW (1) | TWI322813B (is) |
| WO (1) | WO2003059931A1 (is) |
| ZA (1) | ZA200405257B (is) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10213371C1 (de) * | 2002-03-21 | 2003-12-24 | Schering Ag | Verfahren zur Herstellung von 7alpha-Methylsteroiden |
| GB0304927D0 (en) * | 2003-03-04 | 2003-04-09 | Resolution Chemicals Ltd | Process for the production of tibolone |
| KR100716981B1 (ko) * | 2004-09-30 | 2007-05-10 | 삼성전자주식회사 | 대중교통의 최적경로 검색방법 및 이를 이용한 휴대용 기기 |
| US20130123541A1 (en) * | 2009-06-29 | 2013-05-16 | Merz Pharma Gmbh & Co. Kgaa | Method of preparing 3,3,5,5-tetramethylcyclohexanone |
| CN111944001A (zh) * | 2020-07-09 | 2020-11-17 | 浙江神洲药业有限公司 | 一种替勃龙的制备方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3341557A (en) * | 1961-06-05 | 1967-09-12 | Upjohn Co | 7-methyltestosterones |
| US3470216A (en) * | 1966-11-29 | 1969-09-30 | Du Pont | Selected 17,17-difluoro unsaturated androstanes |
| FR2054527B1 (is) * | 1969-07-28 | 1973-06-08 | Roussel Uclaf | |
| US3798213A (en) * | 1971-01-25 | 1974-03-19 | Merck & Co Inc | 7 alpha-methyl-20-spiroxane-3-ones and process |
| DE2558088C2 (de) * | 1975-12-19 | 1985-05-30 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur Herstellung von 4-Androsten-3,17-dion-Derivaten |
| JPS56145239A (en) * | 1980-04-11 | 1981-11-11 | Sumitomo Chem Co Ltd | Novel bicyclooctane derivative and its preparation |
| US4298559A (en) * | 1980-07-23 | 1981-11-03 | Dow Corning Corporation | High yield silicon carbide from alkylated or arylated pre-ceramic polymers |
| US6054446A (en) * | 1997-12-24 | 2000-04-25 | Sri International | Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use |
| US6548491B2 (en) * | 1997-12-24 | 2003-04-15 | Sri International | Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use |
| ATE246703T1 (de) * | 1999-04-06 | 2003-08-15 | Akzo Nobel Nv | Oral wirksame 7-alpha-alkyl androgene |
| TW548277B (en) * | 1999-07-16 | 2003-08-21 | Akzo Nobel Nv | Orally active androgens |
| HUP0203611A3 (en) * | 1999-12-02 | 2004-07-28 | Akzo Nobel Nv | 14,15-beta-methylene substituted androgens and their use for preparation of the medicaments |
| WO2001058919A2 (en) * | 2000-02-11 | 2001-08-16 | Sri International | Synthesis of anti-estrogenic and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one |
| AU8201601A (en) * | 2000-07-28 | 2002-02-13 | Akzo Nobel Nv | 16alpha-methyl or ethyl substituted estrogens |
| US20040010138A1 (en) * | 2002-03-21 | 2004-01-15 | Schering Ag | Process for the production of 7alpha-methyl steroids |
| US7304157B2 (en) * | 2004-09-28 | 2007-12-04 | Bristol-Myers Squibb Company | Efficient synthesis of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones |
-
2003
- 2003-01-14 US US10/502,259 patent/US20050090476A1/en not_active Abandoned
- 2003-01-14 KR KR1020047010985A patent/KR100937179B1/ko active IP Right Grant
- 2003-01-14 EP EP03702441A patent/EP1470151B1/en not_active Expired - Lifetime
- 2003-01-14 AU AU2003205604A patent/AU2003205604B8/en not_active Expired
- 2003-01-14 MX MXPA04007049A patent/MXPA04007049A/es active IP Right Grant
- 2003-01-14 WO PCT/EP2003/000339 patent/WO2003059931A1/en active IP Right Grant
- 2003-01-14 ES ES03702441T patent/ES2336439T3/es not_active Expired - Lifetime
- 2003-01-14 TW TW092100693A patent/TWI322813B/zh not_active IP Right Cessation
- 2003-01-14 RO ROA200400656A patent/RO122913B1/ro unknown
- 2003-01-14 CA CA2472379A patent/CA2472379C/en not_active Expired - Lifetime
- 2003-01-14 RU RU2004125580/04A patent/RU2305105C2/ru active
- 2003-01-14 CN CNB038024918A patent/CN100372864C/zh not_active Expired - Lifetime
- 2003-01-14 RS YUP-630/04A patent/RS51490B/sr unknown
- 2003-01-14 NZ NZ533970A patent/NZ533970A/en not_active IP Right Cessation
- 2003-01-14 PL PL371583A patent/PL208163B1/pl unknown
- 2003-01-14 BR BRPI0306736A patent/BRPI0306736B8/pt not_active IP Right Cessation
- 2003-01-14 AT AT03702441T patent/ATE453659T1/de not_active IP Right Cessation
- 2003-01-14 IL IL16277003A patent/IL162770A0/xx unknown
- 2003-01-14 DE DE60330749T patent/DE60330749D1/de not_active Expired - Lifetime
- 2003-01-14 JP JP2003560033A patent/JP5250174B2/ja not_active Expired - Lifetime
- 2003-01-19 EG EG2003010051A patent/EG23417A/xx active
- 2003-01-20 PE PE2003000062A patent/PE20030926A1/es active IP Right Grant
- 2003-01-20 AR ARP030100149A patent/AR038165A1/es unknown
-
2004
- 2004-06-28 IS IS7339A patent/IS2740B/is unknown
- 2004-06-29 IL IL162770A patent/IL162770A/en active IP Right Grant
- 2004-07-01 ZA ZA2004/05257A patent/ZA200405257B/en unknown
- 2004-07-06 EC EC2004005180A patent/ECSP045180A/es unknown
- 2004-07-12 HR HRP20040634AA patent/HRP20040634B1/hr not_active IP Right Cessation
- 2004-08-19 NO NO20043455A patent/NO327095B1/no not_active IP Right Cessation
-
2010
- 2010-04-22 US US12/765,629 patent/US20100204497A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FR2598421A1 (fr) | Nouveaux produits 19-nor ou 19-nor d-homo steroides substitues en position 11b par un radical phenyle portant un radical alkynyle, leur procede de preparation, leur application comme medicaments et les compositions les renfermant | |
| EP1776378B1 (en) | Process for the preparation 2-substituted-derivatives of estrone and estradiol | |
| NO317879B1 (no) | Androgene steroidforbindelser,fremgangsmate for fremstilling av samme,farmasoytisk innbefattende samme og anvendelse av samme for fremstilling av medikament | |
| US20100204497A1 (en) | Process For The Preparation of 7 alpha-Methylsteroids | |
| NO329563B1 (no) | 9-alfa-substituerte ostratriener som selektivt aktive ostrogener, farmasoytiske preparater som inneholder forbindelsene, samt anvendelse derav til fremstilling av farmasoytiske midler | |
| CN100354299C (zh) | 在11位带有烃取代基的非芳香族雌激素甾族化合物 | |
| EP1608670B1 (en) | Process for the production of tibolone | |
| US20010039269A1 (en) | Synthesis of anti-estrogenic and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one | |
| WO2012020417A1 (en) | Process for the preparation of estradiol and its derivatives | |
| US20060111332A1 (en) | Process and intermediates to prepare17beta-hydroxy-7alpha-methyl-19-nor-17alpha-pregn -5(10)-en-20-yn-3-one | |
| JP2002511481A (ja) | ４，４−ジメチル−５α−コレスタ−８，１４，２４−トリエン−３β−オールの製造方法及び方法（Ｉ）における中間生成物 | |
| TW201418276A (zh) | 製備１７－經取代類固醇之方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: MERCK SHARP & DOHME BV, NL |
|
| MK1K | Patent expired |