FI67538C - Foerfarande foer framstaellning av (z)-1,2-difenyl-1-(4-(2-(n n-dimetylamino)etoxi)fenyl)-1-buten - Google Patents
Foerfarande foer framstaellning av (z)-1,2-difenyl-1-(4-(2-(n n-dimetylamino)etoxi)fenyl)-1-buten Download PDFInfo
- Publication number
- FI67538C FI67538C FI821879A FI821879A FI67538C FI 67538 C FI67538 C FI 67538C FI 821879 A FI821879 A FI 821879A FI 821879 A FI821879 A FI 821879A FI 67538 C FI67538 C FI 67538C
- Authority
- FI
- Finland
- Prior art keywords
- triphenyl
- toluene
- ethoxy
- dimethylamino
- diphenyl
- Prior art date
Links
- -1 ETHOXY Chemical class 0.000 title claims description 119
- 238000000034 method Methods 0.000 title claims description 32
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 title 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- 150000004681 metal hydrides Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
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- 125000000524 functional group Chemical group 0.000 claims description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims 2
- HFHRSBKYURPWRU-UHFFFAOYSA-N 1,1-diphenylbut-3-enylbenzene Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(CC=C)C1=CC=CC=C1 HFHRSBKYURPWRU-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 241000575946 Ione Species 0.000 claims 1
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 claims 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 230000020477 pH reduction Effects 0.000 claims 1
- 239000012071 phase Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 45
- 239000000203 mixture Substances 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
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- 229960001603 tamoxifen Drugs 0.000 description 27
- 238000001704 evaporation Methods 0.000 description 24
- 230000008020 evaporation Effects 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- DCVRPTXKLQTKQZ-UHFFFAOYSA-N 2,3,4-triphenylfuran Chemical compound C=1OC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)C=1C1=CC=CC=C1 DCVRPTXKLQTKQZ-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- YVDXPPVFFOUDJK-UHFFFAOYSA-N [4-[2-(dimethylamino)ethoxy]phenyl]-phenylmethanone Chemical compound C1=CC(OCCN(C)C)=CC=C1C(=O)C1=CC=CC=C1 YVDXPPVFFOUDJK-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 150000001860 citric acid derivatives Chemical class 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000003377 acid catalyst Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 241000723347 Cinnamomum Species 0.000 description 3
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 229940117916 cinnamic aldehyde Drugs 0.000 description 3
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 3
- 235000017803 cinnamon Nutrition 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
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- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- PEKJBXULSNIBAG-UHFFFAOYSA-N C1(=CC=CC=C1)[U](C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)[U](C1=CC=CC=C1)C1=CC=CC=C1 PEKJBXULSNIBAG-UHFFFAOYSA-N 0.000 description 2
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- 241001026509 Kata Species 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
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- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
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- 150000008366 benzophenones Chemical class 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
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- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 150000003459 sulfonic acid esters Chemical class 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- NZBUCABTIWJWAN-UHFFFAOYSA-N tetrabromomethane;triphenylphosphane Chemical compound BrC(Br)(Br)Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NZBUCABTIWJWAN-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N 1,4-butanediol Substances OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 1
- DCYGAPKNVCQNOE-UHFFFAOYSA-N 2,2,2-triphenylacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)O)C1=CC=CC=C1 DCYGAPKNVCQNOE-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
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- 206010006187 Breast cancer Diseases 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
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- 150000008065 acid anhydrides Chemical class 0.000 description 1
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- 230000003197 catalytic effect Effects 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000010666 hydroalumination reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- AESFJDICLJFXLK-UHFFFAOYSA-N iodomethane;triphenyl phosphite Chemical compound IC.C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 AESFJDICLJFXLK-UHFFFAOYSA-N 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- VSWLXYAZJZQIKA-UHFFFAOYSA-N tetrachloromethane;triphenylphosphane Chemical compound ClC(Cl)(Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VSWLXYAZJZQIKA-UHFFFAOYSA-N 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Priority Applications (31)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI821879A FI67538C (fi) | 1982-05-27 | 1982-05-27 | Foerfarande foer framstaellning av (z)-1,2-difenyl-1-(4-(2-(n n-dimetylamino)etoxi)fenyl)-1-buten |
| FI831584A FI77839C (fi) | 1982-05-27 | 1983-05-09 | Foerfarande foer framstaellning av nya terapeutiskt effektiva trifenylalkan- och alkenderivat. |
| LU88803C LU88803I2 (fr) | 1982-05-27 | 1983-05-20 | Fareston |
| CA000428668A CA1185977A (en) | 1982-05-27 | 1983-05-20 | 1,1,2-triphenyl-ethane or ethylene compounds |
| DE8383302912T DE3366021D1 (en) | 1982-05-27 | 1983-05-20 | Novel tri-phenyl alkane and alkene derivatives and their preparation and use |
| AT83302912T ATE22064T1 (de) | 1982-05-27 | 1983-05-20 | Triphenylalkan- bzw. -alkenderivate, ihre herstellung und verwendung. |
| EP83302912A EP0095875B1 (en) | 1982-05-27 | 1983-05-20 | Novel tri-phenyl alkane and alkene derivatives and their preparation and use |
| DD83251216A DD230864A1 (de) | 1982-05-27 | 1983-05-24 | Verfahren zur herstellung neuartiger alkan- und alkenabkoemmlinge |
| AU14946/83A AU556608B2 (en) | 1982-05-27 | 1983-05-25 | Tri-phenyl alkanes (alkenes) |
| NZ204349A NZ204349A (en) | 1982-05-27 | 1983-05-25 | Triphenyl-alkane and-alkene derivatives and pharmaceutical compositions |
| JP58093311A JPS58216129A (ja) | 1982-05-27 | 1983-05-25 | 新規なアルカンおよびアルケン誘導体ならびにそれを有効成分とする医薬 |
| IL68784A IL68784A (en) | 1982-05-27 | 1983-05-25 | Triphenyl ethene and ethane derivatives,their preparation and pharmaceutical compositions containing them |
| ZA833803A ZA833803B (en) | 1982-05-27 | 1983-05-25 | Tri-phenyl alkane and alkene derivatives and their preparation and use |
| DK236583A DK170927B1 (da) | 1982-05-27 | 1983-05-26 | Analogifremgangsmåde til fremstilling af trifenylalkenderivater |
| AT0192983A AT383344B (de) | 1982-05-27 | 1983-05-26 | Verfahren zur herstellung von (z)-1,2-diphenyl-1-(4-(2-(n,n-dimethylamino)eth xy)phenyl)-1-buten |
| NO831874A NO158096C (no) | 1982-05-27 | 1983-05-26 | Fremgangsmaate for fremstilling av terapeutisk aktivt (z)-1,2-difenyl-l-(4-(2-(n,n-dimetylamino)etoksylfenyl)-l-buten (i) eller tamoxifen og syreaddisjonssalter derav. |
| UA3597902A UA5558A1 (uk) | 1982-05-27 | 1983-05-26 | Спосіб отримання алкенових похідних чи їх солей |
| NO831873A NO156164C (no) | 1982-05-27 | 1983-05-26 | Analogifremgangsmaate for fremstilling av nye terapeutisk aktive alkan- og alkenderivater. |
| SU833597902A SU1508955A3 (ru) | 1982-05-27 | 1983-05-26 | Способ получени алкеновых производных или их солей |
| DK236683A DK165785C (da) | 1982-05-27 | 1983-05-26 | Fremgangsmaade til fremstilling af trifenylbutenderivater og farmaceutisk acceptable syreadditionssalte deraf og mellemprodukter til brug ved fremgangsmaaden |
| IE1247/83A IE55023B1 (en) | 1982-05-27 | 1983-05-26 | Novel tri-phenyl alkane and alkene derivatives and their preparation and use |
| SG654/88A SG65488G (en) | 1982-05-27 | 1988-09-30 | Novel tri-phenyl alkane and alkene derivatives and their preparation and use |
| HK8389A HK8389A (en) | 1982-05-27 | 1989-01-26 | Novel tri-phenyl alkane and alkene derivatives and their preparation and use |
| JP2114935A JPH037239A (ja) | 1982-05-27 | 1990-04-26 | 新規なアルカン誘導体の製造法 |
| JP4289137A JPH0678257B2 (ja) | 1982-05-27 | 1992-10-27 | 新規なアルケン誘導体の製造法 |
| JP4289136A JPH0742241B2 (ja) | 1982-05-27 | 1992-10-27 | 新規なアルケン誘導体の製造法 |
| LV920318A LV5066A3 (lv) | 1982-05-27 | 1992-12-17 | Alkenatvasinajumu vai to salu iegusanas metode |
| LTRP766A LT2243B (lt) | 1982-05-27 | 1993-07-07 | Alkenu dariniu ir ju drusku gavimo budas |
| BG098379A BG60760B2 (bg) | 1982-05-27 | 1994-01-18 | Нови трифенилалканови и трифенилалкенови производни, метод за тяхното получаване и използването им |
| NO1996002C NO1996002I1 (no) | 1982-05-27 | 1996-01-26 | (4-klor-1,2-difenyl-1-(4-(2-(N,N.dimetylamino)etoksy)fenyl-1-buten,(Z)-isomer |
| NL960021C NL960021I2 (nl) | 1982-05-27 | 1996-08-14 | Nieuwe trifenylalkaan en alkeenderivaten den de bereiding en toepassing daarvan. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI821879 | 1982-05-27 | ||
| FI821879A FI67538C (fi) | 1982-05-27 | 1982-05-27 | Foerfarande foer framstaellning av (z)-1,2-difenyl-1-(4-(2-(n n-dimetylamino)etoxi)fenyl)-1-buten |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI821879A0 FI821879A0 (fi) | 1982-05-27 |
| FI821879L FI821879L (fi) | 1983-11-28 |
| FI67538B FI67538B (fi) | 1984-12-31 |
| FI67538C true FI67538C (fi) | 1985-04-10 |
Family
ID=8515594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI821879A FI67538C (fi) | 1982-05-27 | 1982-05-27 | Foerfarande foer framstaellning av (z)-1,2-difenyl-1-(4-(2-(n n-dimetylamino)etoxi)fenyl)-1-buten |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS58216129A (enrdf_load_stackoverflow) |
| AT (1) | AT383344B (enrdf_load_stackoverflow) |
| DK (1) | DK165785C (enrdf_load_stackoverflow) |
| FI (1) | FI67538C (enrdf_load_stackoverflow) |
| HK (1) | HK8389A (enrdf_load_stackoverflow) |
| NO (2) | NO158096C (enrdf_load_stackoverflow) |
| ZA (1) | ZA833803B (enrdf_load_stackoverflow) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9126209D0 (en) * | 1991-12-10 | 1992-02-12 | Orion Yhtymae Oy | Drug formulations for parenteral use |
| GB9207437D0 (en) * | 1992-04-03 | 1992-05-20 | Orion Yhtymae Oy | Topical administration of toremifene and its metabolites |
| KR100303634B1 (ko) | 1992-10-27 | 2001-11-22 | 다께다 가즈히꼬 | 자기면역질환치료약 |
| TW593256B (en) * | 1999-11-16 | 2004-06-21 | Hormos Medical Oy Ltd | Triphenylalkene derivatives and their use as selective estrogen receptor modulators |
| FI20030747A0 (fi) * | 2003-05-19 | 2003-05-19 | Orion Corp | Toremifeenin kiteytysmenetelmä |
| CN106397226A (zh) * | 2016-04-19 | 2017-02-15 | 福安药业集团宁波天衡制药有限公司 | 一种他莫昔芬的新制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1079747A (en) * | 1965-07-07 | 1967-08-16 | Ici Ltd | Alkene derivatives |
| HU172948B (hu) * | 1976-02-05 | 1979-01-28 | Gyogyszerkutato Intezet | Sposob poluchenija osnovnykh proizvodnykh trifenil-alkenov |
-
1982
- 1982-05-27 FI FI821879A patent/FI67538C/fi not_active IP Right Cessation
-
1983
- 1983-05-25 JP JP58093311A patent/JPS58216129A/ja active Granted
- 1983-05-25 ZA ZA833803A patent/ZA833803B/xx unknown
- 1983-05-26 AT AT0192983A patent/AT383344B/de not_active IP Right Cessation
- 1983-05-26 DK DK236683A patent/DK165785C/da not_active IP Right Cessation
- 1983-05-26 NO NO831874A patent/NO158096C/no not_active IP Right Cessation
-
1989
- 1989-01-26 HK HK8389A patent/HK8389A/en not_active IP Right Cessation
-
1996
- 1996-01-26 NO NO1996002C patent/NO1996002I1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO158096B (no) | 1988-04-05 |
| DK236683A (da) | 1983-11-28 |
| FI67538B (fi) | 1984-12-31 |
| FI821879A0 (fi) | 1982-05-27 |
| AT383344B (de) | 1987-06-25 |
| ATA192983A (de) | 1986-11-15 |
| NO1996002I1 (no) | 1996-01-26 |
| DK165785B (da) | 1993-01-18 |
| DK165785C (da) | 1993-06-14 |
| NO831874L (no) | 1983-11-28 |
| HK8389A (en) | 1989-02-03 |
| DK236683D0 (da) | 1983-05-26 |
| JPH0419973B2 (enrdf_load_stackoverflow) | 1992-03-31 |
| JPS58216129A (ja) | 1983-12-15 |
| NO158096C (no) | 1988-07-13 |
| ZA833803B (en) | 1984-02-29 |
| FI821879L (fi) | 1983-11-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: FARMOS-YHTYMAE OY |