ZA200404891B - Crystals of bicalutamide and process for their production. - Google Patents
Crystals of bicalutamide and process for their production. Download PDFInfo
- Publication number
- ZA200404891B ZA200404891B ZA200404891A ZA200404891A ZA200404891B ZA 200404891 B ZA200404891 B ZA 200404891B ZA 200404891 A ZA200404891 A ZA 200404891A ZA 200404891 A ZA200404891 A ZA 200404891A ZA 200404891 B ZA200404891 B ZA 200404891B
- Authority
- ZA
- South Africa
- Prior art keywords
- bicalutamide
- production method
- solution
- formula
- ethyl acetate
- Prior art date
Links
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 title claims abstract description 149
- 229960000997 bicalutamide Drugs 0.000 title claims abstract description 149
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 89
- 239000013078 crystal Substances 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 240
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 72
- 239000002904 solvent Substances 0.000 claims description 69
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 claims description 66
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 46
- 239000004215 Carbon black (E152) Substances 0.000 claims description 30
- 229930195733 hydrocarbon Natural products 0.000 claims description 30
- 150000002430 hydrocarbons Chemical class 0.000 claims description 30
- 238000001816 cooling Methods 0.000 claims description 27
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 claims description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 16
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 16
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims description 16
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 16
- 238000001556 precipitation Methods 0.000 claims description 15
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 12
- 239000003444 phase transfer catalyst Substances 0.000 claims description 11
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 claims description 9
- 239000012046 mixed solvent Substances 0.000 claims description 6
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 5
- QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 abstract description 20
- 230000007613 environmental effect Effects 0.000 abstract description 8
- 238000002441 X-ray diffraction Methods 0.000 abstract description 7
- 239000007787 solid Substances 0.000 abstract description 7
- 238000005481 NMR spectroscopy Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 135
- 239000000203 mixture Substances 0.000 description 82
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 54
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- -1 3 Chemical class 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 19
- 238000007254 oxidation reaction Methods 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000007810 chemical reaction solvent Substances 0.000 description 12
- 239000002245 particle Substances 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000006227 byproduct Substances 0.000 description 9
- 150000002009 diols Chemical group 0.000 description 9
- 238000002955 isolation Methods 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
- 239000004593 Epoxy Substances 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UQUQTWDUTIAAAY-UHFFFAOYSA-N n-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C1(C)CO1 UQUQTWDUTIAAAY-UHFFFAOYSA-N 0.000 description 6
- HHWDZLSGDDXUSM-UHFFFAOYSA-N n-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NC1=CC=C(C#N)C(C(F)(F)F)=C1 HHWDZLSGDDXUSM-UHFFFAOYSA-N 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- GCGWWKKSGPETMI-UHFFFAOYSA-N n-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfanyl-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CSC1=CC=C(F)C=C1 GCGWWKKSGPETMI-UHFFFAOYSA-N 0.000 description 5
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 150000003457 sulfones Chemical class 0.000 description 5
- PMDYLCUKSLBUHO-UHFFFAOYSA-N 4-amino-2-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C#N)C(C(F)(F)F)=C1 PMDYLCUKSLBUHO-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 4
- 238000006257 total synthesis reaction Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002924 oxiranes Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 125000000101 thioether group Chemical group 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000004880 explosion Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- DOFAKQUGUJXYPV-UHFFFAOYSA-N 2-hydroxy-2-methyl-n-[3-(trifluoromethyl)phenyl]propanamide Chemical compound CC(C)(O)C(=O)NC1=CC=CC(C(F)(F)F)=C1 DOFAKQUGUJXYPV-UHFFFAOYSA-N 0.000 description 1
- GETMKVRSDFVVHL-UHFFFAOYSA-N 2-methyl-n-[3-(trifluoromethyl)phenyl]propanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C(F)(F)F)=C1 GETMKVRSDFVVHL-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000000449 magic angle spinning nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P5/28—Antiandrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001380686 | 2001-12-13 | ||
| JP2002166213 | 2002-06-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200404891B true ZA200404891B (en) | 2005-06-21 |
Family
ID=26625048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200404891A ZA200404891B (en) | 2001-12-13 | 2004-06-21 | Crystals of bicalutamide and process for their production. |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US6740770B2 (ko) |
| EP (1) | EP1462442B1 (ko) |
| JP (2) | JP4255381B2 (ko) |
| KR (1) | KR100938188B1 (ko) |
| CN (1) | CN1602299A (ko) |
| AT (1) | ATE440817T1 (ko) |
| AU (2) | AU2002354475B2 (ko) |
| BR (1) | BR0214933A (ko) |
| CA (1) | CA2469594C (ko) |
| CY (1) | CY1110550T1 (ko) |
| DE (1) | DE60233526D1 (ko) |
| DK (1) | DK1462442T3 (ko) |
| ES (1) | ES2331178T3 (ko) |
| IL (3) | IL162398A0 (ko) |
| IS (1) | IS2737B (ko) |
| NZ (1) | NZ533943A (ko) |
| PT (1) | PT1462442E (ko) |
| SI (1) | SI1462442T1 (ko) |
| WO (1) | WO2003053920A1 (ko) |
| ZA (1) | ZA200404891B (ko) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU223950B1 (hu) * | 1999-06-10 | 2005-03-29 | Richter Gedeon Vegyészeti Gyár Rt. | Eljárás a racém, valamint az R-(-)- és S-(+)-N-[4-ciano-3-(trifluor-metil)-fenil]-3-[(4-fluor-fenil)-szulfonil]-2-hidroxi-2-metil-propánsavamid előállítására |
| WO2001023521A2 (en) * | 1999-09-29 | 2001-04-05 | The General Hospital Corporation | Polypeptide derivatives of parathyroid hormone (pth) |
| US7102026B2 (en) | 2001-06-13 | 2006-09-05 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Process for preparing and isolating rac-bicalutamide and its intermediates |
| JP4255381B2 (ja) * | 2001-12-13 | 2009-04-15 | 住友化学株式会社 | ビカルタミドの結晶およびその製造方法 |
| US20040063782A1 (en) * | 2002-09-27 | 2004-04-01 | Westheim Raymond J.H. | Bicalutamide forms |
| AU2003209667A1 (en) * | 2003-02-21 | 2004-09-09 | Hetero Drugs Limited | Bicalutamide polymorphs |
| EP1558570A1 (en) * | 2003-06-25 | 2005-08-03 | Teva Gyogyszergyar Reszvenytarsasag | Process for purifying and isolating rac-bicalutamide |
| JP4322621B2 (ja) * | 2003-10-16 | 2009-09-02 | 住友化学株式会社 | ４’−シアノ−３−［（４−フルオロフェニル）スルホニル］−２−ヒドロキシ−２−メチル−３’−トリフルオロメチルプロピオンアニリドの製造方法 |
| WO2005089511A2 (en) * | 2004-03-19 | 2005-09-29 | Transform Pharmaceuticals, Inc. | Novel pharmaceutical forms, and methods of making and using the same |
| US7632971B2 (en) * | 2004-07-14 | 2009-12-15 | Sumitomo Chemical Company, Limited | Method of crystallization of bicalutamide |
| JP2008534575A (ja) * | 2005-03-29 | 2008-08-28 | ユーエスヴィー リミテッド | ビカルタミドの調製のための新規プロセス |
| CA2513356A1 (en) * | 2005-07-26 | 2007-01-26 | Apotex Pharmachem Inc. | Process for production of bicalutamide |
| AU2006329551A1 (en) * | 2005-12-27 | 2007-07-05 | Dabur Pharma Limited | An improved process for preparation of Bicalutamide |
| JP2009067710A (ja) * | 2007-09-12 | 2009-04-02 | Sumitomo Chemical Co Ltd | Ｎ−メタクリロイル−４−シアノ−３−トリフルオロメチルアニリンの製造方法 |
| WO2009087666A2 (en) * | 2008-01-04 | 2009-07-16 | Kekule Pharma | An improved process for production of bicalutamide useful in the treatment of prostate cancer |
| CN101987086B (zh) * | 2009-08-03 | 2012-07-18 | 北京化工大学 | 一种超细比卡鲁胺口服片剂及其制备方法 |
| EP3192464B1 (en) | 2009-11-03 | 2018-08-22 | Howmedica Osteonics Corp. | A kit of surgical instruments for removing a spinal implant |
| CN101891663A (zh) * | 2010-07-21 | 2010-11-24 | 杭州民生药业有限公司 | 一种比卡鲁胺中间体的制备方法 |
| WO2012042532A1 (en) | 2010-09-29 | 2012-04-05 | Shilpa Medicare Limited | Process for preparing bicalutamide |
| CN102321000A (zh) * | 2011-07-21 | 2012-01-18 | 宁波人健药业集团有限公司 | 氧化制备比卡鲁胺的方法 |
| AR089702A1 (es) * | 2012-01-13 | 2014-09-10 | Medeia Therapeutics Ltd | Derivados de heteroarilamida que tienen propiedades antiandrogenicas |
| CN105541680B (zh) * | 2016-02-16 | 2017-12-22 | 重庆硕奥科技有限公司 | 一种比卡鲁胺的合成方法 |
| CN105949095A (zh) * | 2016-05-27 | 2016-09-21 | 山西振东制药股份有限公司 | 一种比卡鲁胺i晶型的制备方法 |
| CN106748884B (zh) * | 2016-12-13 | 2021-08-20 | 山西振东制药股份有限公司 | 一种比卡鲁胺中间体的制备方法 |
| CN106905265A (zh) * | 2017-03-09 | 2017-06-30 | 常州沃腾化工科技有限公司 | N‑[4‑氰基‑3‑（三氟甲基）苯基]‑2,3‑环氧‑2‑甲基丙酰胺的制备方法 |
| CN109336798B (zh) * | 2018-11-19 | 2021-11-16 | 常州新星联生物科技有限公司 | 一种比卡鲁胺硫醚中间体的制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE225694C (ko) | ||||
| US4191775A (en) | 1977-12-15 | 1980-03-04 | Imperial Chemical Industries Limited | Amide derivatives |
| ATE28864T1 (de) * | 1982-07-23 | 1987-08-15 | Ici Plc | Amide-derivate. |
| DD225694A1 (de) * | 1984-06-14 | 1985-08-07 | Univ Leipzig | Verfahren zur darstellung substituierter 9-oxabicyclo/6.1.0/-nonane |
| HU223950B1 (hu) * | 1999-06-10 | 2005-03-29 | Richter Gedeon Vegyészeti Gyár Rt. | Eljárás a racém, valamint az R-(-)- és S-(+)-N-[4-ciano-3-(trifluor-metil)-fenil]-3-[(4-fluor-fenil)-szulfonil]-2-hidroxi-2-metil-propánsavamid előállítására |
| HUP0203785A2 (hu) | 1999-10-19 | 2003-04-28 | Nobex Corporation | Eljárás Casodex enantiomereinek, származékainak és intermediereinek előállítására |
| BR0015124A (pt) | 1999-10-27 | 2002-07-02 | Nobex Corp | Método de preparação de um enanciÈmero substancialmente puro |
| CZ2003836A3 (cs) * | 2000-09-21 | 2003-08-13 | Bristol-Myers Squibb Company | Způsob přípravy N-(substituovaný fenyl)-3-alkyl,-aryl- a -heteroarylsulfonyl-2-hydroxy-2-alkyl-a -halogenalkylpropanamidových sloučenin |
| US6479692B1 (en) | 2001-05-02 | 2002-11-12 | Nobex Corporation | Methods of synthesizing acylanilides including bicalutamide and derivatives thereof |
| AU2002312431A1 (en) | 2001-06-13 | 2002-12-23 | Biogal Gyogyszergyar Rt. | Novel process for preparing rac-bicalutamide and its intermediates |
| US7102026B2 (en) | 2001-06-13 | 2006-09-05 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Process for preparing and isolating rac-bicalutamide and its intermediates |
| JP4255381B2 (ja) * | 2001-12-13 | 2009-04-15 | 住友化学株式会社 | ビカルタミドの結晶およびその製造方法 |
| US20040063782A1 (en) | 2002-09-27 | 2004-04-01 | Westheim Raymond J.H. | Bicalutamide forms |
| US6818766B2 (en) | 2002-10-02 | 2004-11-16 | Synthon Bv | Process for making bicalutamide and intermediates thereof |
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