NO135315B - - Google Patents
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- Publication number
- NO135315B NO135315B NO7121A NO2171A NO135315B NO 135315 B NO135315 B NO 135315B NO 7121 A NO7121 A NO 7121A NO 2171 A NO2171 A NO 2171A NO 135315 B NO135315 B NO 135315B
- Authority
- NO
- Norway
- Prior art keywords
- formula
- tetrahydro
- compound
- rac
- hydrochloride
- Prior art date
Links
- 238000000034 method Methods 0.000 claims abstract description 32
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 230000008569 process Effects 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 98
- -1 di-substituted amino group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 22
- 125000003277 amino group Chemical group 0.000 claims description 21
- 239000012458 free base Substances 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000002378 acidificating effect Effects 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 239000007858 starting material Substances 0.000 claims description 8
- OSZMNJRKIPAVOS-UHFFFAOYSA-N 4-phenyl-1,2,3,4-tetrahydroisoquinoline Chemical class C1NCC2=CC=CC=C2C1C1=CC=CC=C1 OSZMNJRKIPAVOS-UHFFFAOYSA-N 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 238000005661 deetherification reaction Methods 0.000 claims description 7
- ZJDCGVDEEHWEIG-UHFFFAOYSA-N diclofensine Chemical compound C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 ZJDCGVDEEHWEIG-UHFFFAOYSA-N 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- SGTJISQIEGVZGI-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C12=CC=C(O)C=C2CN(C)CC1C1=CC=C(Cl)C(Cl)=C1 SGTJISQIEGVZGI-UHFFFAOYSA-N 0.000 claims description 3
- DFMPEQSDFDFZAQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C12=CC=C(O)C=C2CN(C)CC1C1=CC=C(Cl)C=C1 DFMPEQSDFDFZAQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 238000001953 recrystallisation Methods 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000000243 solution Substances 0.000 description 50
- 239000002585 base Substances 0.000 description 46
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 46
- 238000001704 evaporation Methods 0.000 description 42
- 230000008020 evaporation Effects 0.000 description 42
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 38
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 230000020477 pH reduction Effects 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- 238000002425 crystallisation Methods 0.000 description 27
- 230000008025 crystallization Effects 0.000 description 27
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 235000011167 hydrochloric acid Nutrition 0.000 description 17
- 235000011121 sodium hydroxide Nutrition 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- 238000010992 reflux Methods 0.000 description 14
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
- 239000012279 sodium borohydride Substances 0.000 description 13
- 229910000033 sodium borohydride Inorganic materials 0.000 description 13
- ZJDCGVDEEHWEIG-HNNXBMFYSA-N (4s)-4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1([C@H]2C3=CC=C(C=C3CN(C)C2)OC)=CC=C(Cl)C(Cl)=C1 ZJDCGVDEEHWEIG-HNNXBMFYSA-N 0.000 description 12
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 12
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 10
- 239000007868 Raney catalyst Substances 0.000 description 10
- 229910000564 Raney nickel Inorganic materials 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 238000005245 sintering Methods 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 239000008098 formaldehyde solution Substances 0.000 description 9
- 239000012280 lithium aluminium hydride Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- RTJYPROKPMILEK-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1NCC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 RTJYPROKPMILEK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- ZJDCGVDEEHWEIG-OAHLLOKOSA-N (4r)-4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1([C@@H]2C3=CC=C(C=C3CN(C)C2)OC)=CC=C(Cl)C(Cl)=C1 ZJDCGVDEEHWEIG-OAHLLOKOSA-N 0.000 description 5
- 230000001430 anti-depressive effect Effects 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- PEHOXCSPLOXNOK-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline;hydron;chloride Chemical compound Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 PEHOXCSPLOXNOK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
- 229910003446 platinum oxide Inorganic materials 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 3
- NURFKPOSAJCQTH-UHFFFAOYSA-N 4-(4-chlorophenyl)-6,7-dimethoxy-2-methyl-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1=2C=C(OC)C(OC)=CC=2CN(C)CC1C1=CC=C(Cl)C=C1 NURFKPOSAJCQTH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229960004698 dichlorobenzyl alcohol Drugs 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000002537 isoquinolines Chemical class 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000021419 vinegar Nutrition 0.000 description 3
- 239000000052 vinegar Substances 0.000 description 3
- AKIKYWSEBGSZBD-UHFFFAOYSA-N 2-methyl-1h-isoquinoline Chemical compound C1=CC=C2C=CN(C)CC2=C1 AKIKYWSEBGSZBD-UHFFFAOYSA-N 0.000 description 2
- PBYMYAJONQZORL-UHFFFAOYSA-N 2-methylisoquinoline Natural products C1=CC=C2C(C)=NC=CC2=C1 PBYMYAJONQZORL-UHFFFAOYSA-N 0.000 description 2
- LCJIQLVGZBCSAV-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=2C(OC)=CC=CC=2C(C)NCC1C1=CC=C(Cl)C(Cl)=C1 LCJIQLVGZBCSAV-UHFFFAOYSA-N 0.000 description 2
- HRLGLJUBRANEGZ-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-1,2-dimethyl-3,4-dihydro-1h-isoquinoline Chemical compound C1N(C)C(C)C2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 HRLGLJUBRANEGZ-UHFFFAOYSA-N 0.000 description 2
- SQTQPRPKDZDAGV-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1NC(C)C2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 SQTQPRPKDZDAGV-UHFFFAOYSA-N 0.000 description 2
- UMKZHXUGFJDIQU-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-2-propan-2-yl-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1N(C(C)C)CC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 UMKZHXUGFJDIQU-UHFFFAOYSA-N 0.000 description 2
- SKKMBBLWDNSRLL-UHFFFAOYSA-N 4-(3-chlorophenyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1NCC2=CC(OC)=CC=C2C1C1=CC=CC(Cl)=C1 SKKMBBLWDNSRLL-UHFFFAOYSA-N 0.000 description 2
- CYWOYWVGDXGPCG-UHFFFAOYSA-N 4-(3-chlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=CC(Cl)=C1 CYWOYWVGDXGPCG-UHFFFAOYSA-N 0.000 description 2
- VGZDOZROHWTHQP-UHFFFAOYSA-N 4-(4-chlorophenyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1NCC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C=C1 VGZDOZROHWTHQP-UHFFFAOYSA-N 0.000 description 2
- LOVFKDKOAPQDNK-UHFFFAOYSA-N 4-(4-chlorophenyl)-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=C(Cl)C=C1 LOVFKDKOAPQDNK-UHFFFAOYSA-N 0.000 description 2
- JWQCNUWRYVLUPL-UHFFFAOYSA-N 4-(7-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-4-yl)aniline;dihydrochloride Chemical compound Cl.Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=C(N)C=C1 JWQCNUWRYVLUPL-UHFFFAOYSA-N 0.000 description 2
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 2
- LCIZALBRTMPJEE-UHFFFAOYSA-N 7-methoxy-2-methyl-4-(3-nitrophenyl)-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=CC([N+]([O-])=O)=C1 LCIZALBRTMPJEE-UHFFFAOYSA-N 0.000 description 2
- VKWRGVQUOMQCMH-UHFFFAOYSA-N 7-methoxy-2-methyl-4-(4-nitrophenyl)-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1N(C)CC2=CC(OC)=CC=C2C1C1=CC=C([N+]([O-])=O)C=C1 VKWRGVQUOMQCMH-UHFFFAOYSA-N 0.000 description 2
- PXZLUIQRFAUJRK-UHFFFAOYSA-N 7-methoxy-4-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1NCC2=CC(OC)=CC=C2C1C1=CC=C([N+]([O-])=O)C=C1 PXZLUIQRFAUJRK-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010015995 Eyelid ptosis Diseases 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- WVYBKVIVGZLWOS-UHFFFAOYSA-N benzyloxidanium;chloride Chemical compound Cl.OCC1=CC=CC=C1 WVYBKVIVGZLWOS-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- JMSRBKPMLUGHCR-UHFFFAOYSA-N bromohydrin Chemical compound BrC[C]1CO1 JMSRBKPMLUGHCR-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000009194 climbing Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- OVHDZBAFUMEXCX-UHFFFAOYSA-N benzyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=CC=CC=C1 OVHDZBAFUMEXCX-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
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- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- YALYLPKSKBQFJP-UHFFFAOYSA-N chloroform;n-ethylethanamine Chemical compound ClC(Cl)Cl.CCNCC YALYLPKSKBQFJP-UHFFFAOYSA-N 0.000 description 1
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- 239000012043 crude product Substances 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
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- 238000006264 debenzylation reaction Methods 0.000 description 1
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- 238000006297 dehydration reaction Methods 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 239000003814 drug Substances 0.000 description 1
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- 238000001640 fractional crystallisation Methods 0.000 description 1
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- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- IYRMNDOLPONSCJ-UHFFFAOYSA-N isoquinolin-2-ium;chloride Chemical compound Cl.C1=NC=CC2=CC=CC=C21 IYRMNDOLPONSCJ-UHFFFAOYSA-N 0.000 description 1
- WCRKBMABEPCYII-UHFFFAOYSA-N isoquinolin-7-ol Chemical class C1=CN=CC2=CC(O)=CC=C21 WCRKBMABEPCYII-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
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- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO740555A NO740555L (no) | 1970-01-06 | 1974-02-19 | Isokinolinderivater til anvendelse som mellomprodukter for fremstilling av 2-alkyl- eller 2-fenyl-lavere alkyl-1,2,3,4-tetrahydro-4-isokinolinderivater. |
| NO740554A NO135062C (nl) | 1970-01-06 | 1974-02-19 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH10370A CH527194A (de) | 1970-01-06 | 1970-01-06 | Verfahren zur Herstellung von Isochinolin-Derivaten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO135315B true NO135315B (nl) | 1976-12-13 |
| NO135315C NO135315C (nl) | 1977-03-23 |
Family
ID=4179328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO7121A NO135315C (nl) | 1970-01-06 | 1971-01-05 |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS5515476B1 (nl) |
| AT (1) | AT303041B (nl) |
| BE (1) | BE761219A (nl) |
| CA (1) | CA999866A (nl) |
| CH (2) | CH538477A (nl) |
| DE (1) | DE2062001C2 (nl) |
| DK (1) | DK125021B (nl) |
| ES (1) | ES387016A1 (nl) |
| FI (1) | FI49503C (nl) |
| FR (1) | FR2081412B1 (nl) |
| GB (1) | GB1335261A (nl) |
| IE (1) | IE34859B1 (nl) |
| IL (1) | IL35916A (nl) |
| NL (1) | NL171444C (nl) |
| NO (1) | NO135315C (nl) |
| PH (1) | PH9682A (nl) |
| SE (3) | SE368401B (nl) |
| YU (1) | YU33660B (nl) |
| ZA (1) | ZA708590B (nl) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA844402B (en) * | 1983-06-23 | 1986-01-29 | Mcneil Pharmaceutical | Hexahydropyrrolo(2,1-a)isoquinoline derivatives |
| US4595688A (en) * | 1983-06-23 | 1986-06-17 | Mcneilab, Inc. | Hexahydropyrrolo[2,1-a]isoquinoline derivatives and antidepressant use thereof |
| US4719216A (en) * | 1983-06-23 | 1988-01-12 | Mcneilab, Inc. | Hexahydropyrrolo(2,1-A)isoquinoline derivatives as antidepressants |
| GB2271566A (en) * | 1992-10-14 | 1994-04-20 | Merck & Co Inc | HIV integrase inhibitors |
| DK1246806T3 (da) | 1999-11-03 | 2008-06-16 | Amr Technology Inc | Aryl- og heteroarylsubstituerede tetrahydroisoquinoliner og anvendelse deraf til blokering af genoptagelse af norepinefrin, dopsmin og serotonin |
| US7163949B1 (en) * | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
| KR100878855B1 (ko) * | 1999-11-03 | 2009-01-15 | 에이엠알 테크놀로지, 인크. | 4-페닐-치환 테트라히드로이소퀴놀린, 및 노르에피네프린과 도파민과 세로토닌의 재흡수를 차단하기 위한 이의 용도 |
| EP1113007A1 (en) * | 1999-12-24 | 2001-07-04 | Pfizer Inc. | Tetrahydroisoquinoline compounds as estrogen agonists/antagonists |
| EP1299393A2 (en) | 2000-07-11 | 2003-04-09 | Bristol-Myers Squibb Pharma Company | 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof |
| NZ552397A (en) | 2004-07-15 | 2011-04-29 | Amr Technology Inc | Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| JP2008543880A (ja) | 2005-06-17 | 2008-12-04 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ナフチリジン化合物 |
| KR20080044840A (ko) | 2005-07-15 | 2008-05-21 | 에이엠알 테크놀로지, 인크. | 아릴- 및 헤테로아릴-치환된 테트라히드로벤자제핀, 및노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기위한 용도 |
| US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
| AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
| WO2010132442A1 (en) | 2009-05-12 | 2010-11-18 | Albany Molecular Reserch, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
| EP2429295B1 (en) | 2009-05-12 | 2013-12-25 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
| EP2429293B1 (en) | 2009-05-12 | 2014-10-29 | Bristol-Myers Squibb Company | CRYSTALLINE FORMS OF (S)-7-([1,2,4]TRIAZOLO[1,5-a]PYRIDIN-6-YL)-4-(3,4-DICHLOROHPHENYL)-1,2,3,4-TETRAHYDROISOQUINOLINE AND USE THEREOF |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670694B2 (de) * | 1966-05-05 | 1976-07-22 | Hoechst Ag, 6000 Frankfurt | Verfahren zur herstellung von tetrahydroisochinolinen |
-
1970
- 1970-01-06 CH CH1011872A patent/CH538477A/de not_active IP Right Cessation
- 1970-01-06 CH CH10370A patent/CH527194A/de not_active IP Right Cessation
- 1970-12-16 DE DE2062001A patent/DE2062001C2/de not_active Expired
- 1970-12-16 SE SE17063/70A patent/SE368401B/xx unknown
- 1970-12-16 SE SE7313623A patent/SE386672B/xx unknown
- 1970-12-21 ZA ZA708590A patent/ZA708590B/xx unknown
- 1970-12-28 IL IL35916A patent/IL35916A/xx unknown
- 1970-12-29 NL NLAANVRAGE7018956,A patent/NL171444C/nl not_active IP Right Cessation
- 1970-12-31 FI FI703519A patent/FI49503C/fi active
-
1971
- 1971-01-04 IE IE6/71A patent/IE34859B1/xx unknown
- 1971-01-05 BE BE761219A patent/BE761219A/xx not_active IP Right Cessation
- 1971-01-05 NO NO7121A patent/NO135315C/no unknown
- 1971-01-05 GB GB45471A patent/GB1335261A/en not_active Expired
- 1971-01-05 FR FR7100097A patent/FR2081412B1/fr not_active Expired
- 1971-01-05 DK DK2571AA patent/DK125021B/da not_active IP Right Cessation
- 1971-01-05 ES ES387016A patent/ES387016A1/es not_active Expired
- 1971-01-05 AT AT4571A patent/AT303041B/de not_active IP Right Cessation
- 1971-01-06 YU YU19/71A patent/YU33660B/xx unknown
- 1971-01-06 JP JP7194A patent/JPS5515476B1/ja active Pending
- 1971-01-06 CA CA102,060A patent/CA999866A/en not_active Expired
- 1971-01-07 PH PH12087*UA patent/PH9682A/en unknown
-
1973
- 1973-10-05 SE SE7313622A patent/SE399879B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA999866A (en) | 1976-11-16 |
| PH9682A (en) | 1976-02-10 |
| IL35916A0 (en) | 1971-02-25 |
| CH527194A (de) | 1972-08-31 |
| SE399879B (sv) | 1978-03-06 |
| JPS5515476B1 (nl) | 1980-04-23 |
| IL35916A (en) | 1973-11-28 |
| FI49503C (fi) | 1975-07-10 |
| FR2081412B1 (nl) | 1974-04-12 |
| FI49503B (nl) | 1975-04-01 |
| FR2081412A1 (nl) | 1971-12-03 |
| DE2062001A1 (de) | 1971-07-15 |
| YU33660B (en) | 1977-12-31 |
| GB1335261A (en) | 1973-10-24 |
| YU1971A (en) | 1977-06-30 |
| NL171444B (nl) | 1982-11-01 |
| BE761219A (fr) | 1971-07-05 |
| IE34859L (en) | 1971-07-06 |
| AT303041B (de) | 1972-11-10 |
| ES387016A1 (es) | 1976-05-01 |
| DK125021B (da) | 1972-12-18 |
| ZA708590B (en) | 1971-09-29 |
| IE34859B1 (en) | 1975-09-03 |
| DE2062001C2 (de) | 1986-10-16 |
| NL7018956A (nl) | 1971-07-08 |
| CH538477A (de) | 1973-06-30 |
| SE368401B (nl) | 1974-07-01 |
| NL171444C (nl) | 1983-04-05 |
| NO135315C (nl) | 1977-03-23 |
| SE386672B (sv) | 1976-08-16 |
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