NO325150B1 - Sulfonyloksyeddiksyreesterderivater, fremgangsmate for deres fremstilling samt deres anvendelse som syntesemellomprodukter - Google Patents
Sulfonyloksyeddiksyreesterderivater, fremgangsmate for deres fremstilling samt deres anvendelse som syntesemellomprodukter Download PDFInfo
- Publication number
- NO325150B1 NO325150B1 NO20001736A NO20001736A NO325150B1 NO 325150 B1 NO325150 B1 NO 325150B1 NO 20001736 A NO20001736 A NO 20001736A NO 20001736 A NO20001736 A NO 20001736A NO 325150 B1 NO325150 B1 NO 325150B1
- Authority
- NO
- Norway
- Prior art keywords
- stated
- group
- chlorophenyl
- methyl
- acid ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 43
- -1 Sulfonyloxyacetic acid ester Chemical class 0.000 title claims description 35
- 238000002360 preparation method Methods 0.000 title description 6
- 239000000543 intermediate Substances 0.000 title description 5
- 239000002253 acid Substances 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 24
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 24
- 229960003009 clopidogrel Drugs 0.000 claims description 24
- 150000002148 esters Chemical class 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- AOGSMZZEIDWJOW-CQSZACIVSA-N methyl (2r)-2-(benzenesulfonyloxy)-2-(2-chlorophenyl)acetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=CC=CC=C1 AOGSMZZEIDWJOW-CQSZACIVSA-N 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 8
- 239000002585 base Substances 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 229910003002 lithium salt Inorganic materials 0.000 claims description 7
- 159000000002 lithium salts Chemical class 0.000 claims description 7
- 150000004982 aromatic amines Chemical class 0.000 claims description 6
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 claims description 6
- 229910001486 lithium perchlorate Inorganic materials 0.000 claims description 6
- BPBBJZNRUKPSDJ-CQSZACIVSA-N methyl (2r)-2-(2-chlorophenyl)-2-(4-nitrophenyl)sulfonyloxyacetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 BPBBJZNRUKPSDJ-CQSZACIVSA-N 0.000 claims description 6
- 239000002798 polar solvent Substances 0.000 claims description 6
- WRNCAJVYSZFDPH-CQSZACIVSA-N methyl (2r)-2-(2-chlorophenyl)-2-(2,5-dichlorophenyl)sulfonyloxyacetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=CC(Cl)=CC=C1Cl WRNCAJVYSZFDPH-CQSZACIVSA-N 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
- 230000022244 formylation Effects 0.000 claims description 3
- 238000006170 formylation reaction Methods 0.000 claims description 3
- 229910001496 lithium tetrafluoroborate Inorganic materials 0.000 claims description 3
- YPCYCGGEMDSLDC-MRXNPFEDSA-N methyl (2r)-2-(2-chlorophenyl)-2-(2,4,6-trimethylphenyl)sulfonyloxyacetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=C(C)C=C(C)C=C1C YPCYCGGEMDSLDC-MRXNPFEDSA-N 0.000 claims description 3
- CIBFZAMKUSNKFH-CQSZACIVSA-N methyl (2r)-2-(2-chlorophenyl)-2-(4-chlorophenyl)sulfonyloxyacetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=CC=C(Cl)C=C1 CIBFZAMKUSNKFH-CQSZACIVSA-N 0.000 claims description 3
- PINYXVRQIQKIJN-JOCHJYFZSA-N methyl (2r)-2-(2-chlorophenyl)-2-[2,4,6-tri(propan-2-yl)phenyl]sulfonyloxyacetate Chemical group O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=C(C(C)C)C=C(C(C)C)C=C1C(C)C PINYXVRQIQKIJN-JOCHJYFZSA-N 0.000 claims description 3
- 239000012454 non-polar solvent Substances 0.000 claims description 3
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
- HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical class NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- 150000001412 amines Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical group O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000005587 carbonate group Chemical group 0.000 claims 1
- 150000008282 halocarbons Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 125000003118 aryl group Chemical group 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- OGUWOLDNYOTRBO-UHFFFAOYSA-N 4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1NCCC2=C1C=CS2 OGUWOLDNYOTRBO-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- ZMPGBVQQIQSQED-MRVPVSSYSA-N methyl (2r)-2-(2-chlorophenyl)-2-hydroxyacetate Chemical compound COC(=O)[C@H](O)C1=CC=CC=C1Cl ZMPGBVQQIQSQED-MRVPVSSYSA-N 0.000 description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- RWOLDZZTBNYTMS-SSDOTTSWSA-N (2r)-2-(2-chlorophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1Cl RWOLDZZTBNYTMS-SSDOTTSWSA-N 0.000 description 4
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- BUGNHCGQRDZRSQ-UHFFFAOYSA-N methyl 2-chloro-2-(2-chlorophenyl)acetate Chemical compound COC(=O)C(Cl)C1=CC=CC=C1Cl BUGNHCGQRDZRSQ-UHFFFAOYSA-N 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- CJPVPOYTTALCNX-UHFFFAOYSA-N (2-chlorophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1Cl CJPVPOYTTALCNX-UHFFFAOYSA-N 0.000 description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- RWOLDZZTBNYTMS-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1Cl RWOLDZZTBNYTMS-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LKLLNYWECKEQIB-UHFFFAOYSA-N 1,3,5-triazinane Chemical compound C1NCNCN1 LKLLNYWECKEQIB-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical class O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- FDEODCTUSIWGLK-RSAXXLAASA-N clopidogrel sulfate Chemical compound [H+].OS([O-])(=O)=O.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl FDEODCTUSIWGLK-RSAXXLAASA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- JYAHLZXGPKGNJS-SECBINFHSA-N methyl (2R)-2-(2-chlorophenyl)-2-methylsulfonyloxyacetate Chemical compound COC(=O)[C@H](OS(C)(=O)=O)C1=CC=CC=C1Cl JYAHLZXGPKGNJS-SECBINFHSA-N 0.000 description 1
- PDIIKCXDULBMTD-OAHLLOKOSA-N methyl (2r)-2-(2-chlorophenyl)-2-(4-methylphenyl)sulfonyloxyacetate Chemical compound O([C@@H](C(=O)OC)C=1C(=CC=CC=1)Cl)S(=O)(=O)C1=CC=C(C)C=C1 PDIIKCXDULBMTD-OAHLLOKOSA-N 0.000 description 1
- BUGNHCGQRDZRSQ-QMMMGPOBSA-N methyl (2s)-2-chloro-2-(2-chlorophenyl)acetate Chemical compound COC(=O)[C@@H](Cl)C1=CC=CC=C1Cl BUGNHCGQRDZRSQ-QMMMGPOBSA-N 0.000 description 1
- XEUQMYXHUMKCJY-UHFFFAOYSA-N methyl 2-methylsulfonyloxypropanoate Chemical compound COC(=O)C(C)OS(C)(=O)=O XEUQMYXHUMKCJY-UHFFFAOYSA-N 0.000 description 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Cephalosporin Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9712441A FR2769313B1 (fr) | 1997-10-06 | 1997-10-06 | Derives d'esters hydroxyacetiques, leur procede de preparation et leur utilisation comme intermediaires de synthese |
| PCT/FR1998/002082 WO1999018110A1 (fr) | 1997-10-06 | 1998-09-29 | Derives d'esters hydroxyacetiques, leur procede de preparation et leur utilisation comme intermediaires de synthese |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20001736D0 NO20001736D0 (no) | 2000-04-04 |
| NO20001736L NO20001736L (no) | 2000-06-06 |
| NO325150B1 true NO325150B1 (no) | 2008-02-11 |
Family
ID=9511879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20001736A NO325150B1 (no) | 1997-10-06 | 2000-04-04 | Sulfonyloksyeddiksyreesterderivater, fremgangsmate for deres fremstilling samt deres anvendelse som syntesemellomprodukter |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US6573381B1 (hu) |
| EP (1) | EP1021449B1 (hu) |
| JP (3) | JP3827946B2 (hu) |
| AT (1) | ATE211476T1 (hu) |
| AU (1) | AU9354498A (hu) |
| BR (1) | BR9813022B1 (hu) |
| CA (1) | CA2306409C (hu) |
| DE (1) | DE69803397T2 (hu) |
| DK (1) | DK1021449T3 (hu) |
| ES (1) | ES2171040T3 (hu) |
| FR (1) | FR2769313B1 (hu) |
| HU (1) | HU226771B1 (hu) |
| NO (1) | NO325150B1 (hu) |
| PT (1) | PT1021449E (hu) |
| WO (1) | WO1999018110A1 (hu) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002018357A1 (en) * | 2000-08-29 | 2002-03-07 | Rpg Life Sciences Limited | A ONE-POT PROCESS FOR THE PREPARATION OF PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS OF 4, 5, 6, 7 - TETRAHYDROTHIENO (3,2-c) PYRIDINE DERIVATIVES HAVING ANTITHROMBOTIC ACTIVITY |
| US6495691B1 (en) | 2001-07-06 | 2002-12-17 | Brantford Chemicals Inc. | Process for the preparation of tetrahydrothieno[3,2-c]pyridine derivatives |
| KR100839136B1 (ko) * | 2001-12-18 | 2008-06-20 | 테바 파마슈티컬 인더스트리즈 리미티드 | 클로피도그렐 황산수소염의 다형 |
| US6767913B2 (en) | 2001-12-18 | 2004-07-27 | Teva Pharmaceutical Industries Ltd. | Crystal forms iii, iv, v, and novel amorphous form of clopidogrel hydrogensulfate, processes for their preparation, processes for the preparation of form i, compositions containing the new forms and methods of administering the new forms |
| US7074928B2 (en) | 2002-01-11 | 2006-07-11 | Teva Pharmaceutical Industries, Ltd. | Polymorphs of clopidogrel hydrogensulfate |
| ITMI20020933A1 (it) * | 2002-05-03 | 2003-11-03 | Danimite Dipharma S P A | Procedimento per la sintesi di clopidogrel |
| IL166593A0 (en) | 2002-08-02 | 2006-01-15 | Racemization and enantiomer separation of clopidogrel | |
| US6800759B2 (en) | 2002-08-02 | 2004-10-05 | Teva Pharmaceutical Industries Ltd. | Racemization and enantiomer separation of clopidogrel |
| ITMI20022228A1 (it) * | 2002-10-21 | 2004-04-22 | Dinamite Dipharma S P A | Sali di clopidogrel con acidi alchil-solforici. |
| WO2004081016A1 (en) | 2003-03-12 | 2004-09-23 | Cadila Healthcare Limited | Polymorphs and amorphous form of (s) - (+) -clopidogrel bisulfate |
| AU2003241149A1 (en) * | 2003-05-05 | 2004-11-26 | Hetero Drugs Limited | Amorphous clopidogrel hydrogen sulfate composition |
| CA2676121A1 (en) | 2003-11-03 | 2005-07-14 | Cadila Healthcare Limited | Processes for preparing different forms of (s)-(+)-clopidogrel bisulfate |
| PL1589019T3 (pl) | 2004-04-20 | 2008-12-31 | Ratiopharm Gmbh | Stereoselektywny sposób wytwarzania klopidogrelu |
| CZ295920B6 (cs) * | 2004-10-18 | 2005-11-16 | Zentiva, A. S | Způsob výroby klopidogrelu |
| CN100406568C (zh) * | 2005-02-18 | 2008-07-30 | 淮北市辉克药业有限公司 | 氯吡格雷新生产工艺 |
| WO2007032023A2 (en) * | 2005-07-12 | 2007-03-22 | Rpg Life Sciences Limited | A process for preparation of methyl-(+)-(s)-alpha-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4h)-acetic acid methyl ester or salts thereof having higher chiral purity and products thereof |
| CN101253271A (zh) * | 2005-09-02 | 2008-08-27 | 第一精密化学株式会社 | 光学活性α-羟基羧酸的制造方法 |
| KR101235117B1 (ko) | 2005-12-26 | 2013-02-20 | 에스케이케미칼주식회사 | 광학분리에 의한 (ｓ)-(＋)-클로피도그렐의 제조방법 |
| WO2007144729A1 (en) * | 2006-06-13 | 2007-12-21 | Orchid Chemicals & Pharmaceuticals Limited | An improved process for the preparation of clopidogrel |
| WO2008004249A2 (en) * | 2006-07-04 | 2008-01-10 | Msn Laboratories Limited | An improved process for the preparation of clopidogrel and its pharmaceutically acceptable salts |
| AU2007280428B2 (en) * | 2006-08-04 | 2012-04-12 | Merz Pharma Gmbh & Co. Kgaa | Substituted pyrazolopyrimidines, a process for their preparation and their use as medicine |
| KR100834967B1 (ko) * | 2006-08-11 | 2008-06-03 | 에스케이케미칼주식회사 | 여액의 라세미화 반응에 의한 ｓ-(＋)-클로피도그렐의고수율 제조방법 |
| EP1980563A1 (en) | 2007-04-09 | 2008-10-15 | BATTULA, Srinivasa Reddy | Procedure for the preparation of methyl (+)-(S)-Alpha-(O-chlorophenyl)-6,7-dihydrothieno-[3,2-C]pyridine-5(4H) acetate |
| BRPI0803101A2 (pt) * | 2007-04-18 | 2014-04-22 | Teva Pharma | Processos melhores para preparação de clopidogrel |
| EP2152078B8 (en) | 2007-04-27 | 2021-03-17 | CyDex Pharmaceuticals, Inc. | Formulations containing clopidogrel and sulfoalkyl ether cyclodextrin and methods of use |
| EP2107061A1 (en) | 2008-04-02 | 2009-10-07 | Krka Tovarna Zdravil, D.D., Novo Mesto | Process for the preparation of optically enriched clopidogrel |
| KR100990949B1 (ko) | 2008-06-09 | 2010-10-29 | 엔자이텍 주식회사 | 클로피도그렐 및 그의 유도체의 제조방법 |
| US8236782B2 (en) | 2009-05-13 | 2012-08-07 | Cydex Pharmaceuticals, Inc. | Pharmaceutical compositions comprising prasugrel and cyclodextrin derivatives and methods of making and using the same |
| CN102120744B (zh) * | 2010-02-02 | 2013-01-09 | 江苏威凯尔医药科技有限公司 | 光学活性2-羟基四氢噻吩并吡啶衍生物及其制备方法与在制药中的用途 |
| CN102558138A (zh) * | 2010-12-08 | 2012-07-11 | 湖北成田制药股份有限公司 | 2-卤代苯基-2-(2-噻吩乙氨基)乙酸酯类及其盐的制备方法 |
| WO2012123958A1 (en) | 2011-02-14 | 2012-09-20 | Cadila Healthcare Limited | Highly pure salts of clopidogrel free of genotoxic impurities |
| CN102351877B (zh) * | 2011-08-12 | 2014-07-09 | 天津药物研究院 | 噻吩衍生物、其制备方法和用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2530247B1 (fr) * | 1982-07-13 | 1986-05-16 | Sanofi Sa | Nouveaux derives de la thieno (3, 2-c) pyridine, leur procede de preparation et leur application therapeutique |
| FR2623810B2 (fr) * | 1987-02-17 | 1992-01-24 | Sanofi Sa | Sels de l'alpha-(tetrahydro-4,5,6,7 thieno(3,2-c) pyridyl-5) (chloro-2 phenyl) -acetate de methyle dextrogyre et compositions pharmaceutiques en contenant |
| FR2652575B1 (fr) * | 1989-09-29 | 1992-01-24 | Sanofi Sa | Procede de preparation d'acides alpha-bromo phenylacetiques. |
| US5189170A (en) | 1989-09-29 | 1993-02-23 | Sanofi | Process for the preparation of phenylacetic derivatives of thieno-pyridines |
| FR2664276B1 (fr) * | 1990-07-04 | 1992-10-23 | Sanofi Sa | Derive thienyl-2 glycidique, son procede de preparation et son utilisation comme intermediaire de synthese. |
| FR2664596B1 (fr) * | 1990-07-10 | 1994-06-10 | Sanofi Sa | Procede de preparation d'un derive n-phenylacetique de tetrahydrothieno [3,2-c] pyridine et son intermediaire de synthese. |
| JPH06293729A (ja) * | 1993-04-06 | 1994-10-21 | Sankyo Co Ltd | 光学活性カルボン酸誘導体 |
| US5583147A (en) * | 1994-03-23 | 1996-12-10 | The Dupont Merck Pharmaceutical Company | Amides for the treatment of atherosclerosis |
| FR2751540B1 (fr) * | 1996-07-26 | 1998-10-16 | Sanofi Sa | Composition pharmaceutique antithrombotique |
| HU222283B1 (hu) * | 1997-05-13 | 2003-05-28 | Sanofi-Synthelabo | Eljárás tieno[3,2-c]piridin-származékok előállítására |
-
1997
- 1997-10-06 FR FR9712441A patent/FR2769313B1/fr not_active Expired - Lifetime
-
1998
- 1998-09-29 DK DK98946523T patent/DK1021449T3/da active
- 1998-09-29 AT AT98946523T patent/ATE211476T1/de active
- 1998-09-29 CA CA2306409A patent/CA2306409C/fr not_active Expired - Lifetime
- 1998-09-29 BR BRPI9813022-6A patent/BR9813022B1/pt not_active IP Right Cessation
- 1998-09-29 AU AU93544/98A patent/AU9354498A/en not_active Abandoned
- 1998-09-29 WO PCT/FR1998/002082 patent/WO1999018110A1/fr active IP Right Grant
- 1998-09-29 HU HU0004250A patent/HU226771B1/hu unknown
- 1998-09-29 JP JP2000514920A patent/JP3827946B2/ja not_active Expired - Lifetime
- 1998-09-29 ES ES98946523T patent/ES2171040T3/es not_active Expired - Lifetime
- 1998-09-29 DE DE69803397T patent/DE69803397T2/de not_active Expired - Lifetime
- 1998-09-29 EP EP98946523A patent/EP1021449B1/fr not_active Expired - Lifetime
- 1998-09-29 PT PT98946523T patent/PT1021449E/pt unknown
- 1998-09-29 US US09/509,879 patent/US6573381B1/en not_active Expired - Lifetime
-
2000
- 2000-04-04 NO NO20001736A patent/NO325150B1/no not_active IP Right Cessation
-
2003
- 2003-04-29 US US10/425,437 patent/US6894186B2/en not_active Expired - Lifetime
-
2004
- 2004-07-14 US US10/890,749 patent/US7153969B2/en not_active Expired - Lifetime
-
2005
- 2005-12-20 JP JP2005366868A patent/JP4264437B2/ja not_active Expired - Lifetime
-
2009
- 2009-01-08 JP JP2009002505A patent/JP4903819B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001519353A (ja) | 2001-10-23 |
| DE69803397T2 (de) | 2002-08-29 |
| US7153969B2 (en) | 2006-12-26 |
| HUP0004250A2 (hu) | 2001-10-28 |
| CA2306409C (fr) | 2010-06-29 |
| BR9813022B1 (pt) | 2010-07-13 |
| AU9354498A (en) | 1999-04-27 |
| JP4903819B2 (ja) | 2012-03-28 |
| NO20001736D0 (no) | 2000-04-04 |
| BR9813022A (pt) | 2000-08-15 |
| HUP0004250A3 (en) | 2001-12-28 |
| NO20001736L (no) | 2000-06-06 |
| CA2306409A1 (fr) | 1999-04-15 |
| JP2006124398A (ja) | 2006-05-18 |
| HU226771B1 (en) | 2009-09-28 |
| DK1021449T3 (da) | 2002-04-22 |
| JP2009137989A (ja) | 2009-06-25 |
| PT1021449E (pt) | 2002-06-28 |
| FR2769313A1 (fr) | 1999-04-09 |
| WO1999018110A1 (fr) | 1999-04-15 |
| JP4264437B2 (ja) | 2009-05-20 |
| US20030208077A1 (en) | 2003-11-06 |
| DE69803397D1 (de) | 2002-02-28 |
| FR2769313B1 (fr) | 2000-04-21 |
| ATE211476T1 (de) | 2002-01-15 |
| US6894186B2 (en) | 2005-05-17 |
| EP1021449A1 (fr) | 2000-07-26 |
| EP1021449B1 (fr) | 2002-01-02 |
| ES2171040T3 (es) | 2002-08-16 |
| US6573381B1 (en) | 2003-06-03 |
| JP3827946B2 (ja) | 2006-09-27 |
| US20040260110A1 (en) | 2004-12-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |