CS229924B2 - Production method of new phenylalkylamine - Google Patents
Production method of new phenylalkylamine Download PDFInfo
- Publication number
- CS229924B2 CS229924B2 CS819178A CS917881A CS229924B2 CS 229924 B2 CS229924 B2 CS 229924B2 CS 819178 A CS819178 A CS 819178A CS 917881 A CS917881 A CS 917881A CS 229924 B2 CS229924 B2 CS 229924B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- group
- amino
- ethanol
- propyl
- methoxyphenyl
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- -1 hydroxymethylene group Chemical group 0.000 claims abstract description 196
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 13
- 125000003277 amino group Chemical group 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 230000003287 optical effect Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 71
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 71
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 229910052801 chlorine Chemical group 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 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
- 238000009835 boiling Methods 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 150000004678 hydrides Chemical class 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052987 metal hydride Inorganic materials 0.000 claims description 3
- 150000004681 metal hydrides Chemical class 0.000 claims description 3
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000075 primary alcohol group Chemical group 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 150000003333 secondary alcohols Chemical class 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims 2
- 229910000085 borane Inorganic materials 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 12
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 125000004434 sulfur atom Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 273
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 243
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
- 229940073584 methylene chloride Drugs 0.000 description 90
- 238000002211 ultraviolet spectrum Methods 0.000 description 78
- 239000000047 product Substances 0.000 description 60
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 57
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 55
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 52
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 40
- 239000000155 melt Substances 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 238000001228 spectrum Methods 0.000 description 27
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
- 125000001931 aliphatic group Chemical group 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 17
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 238000005245 sintering Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ATKJJUFAWYSFID-UHFFFAOYSA-N 1-(4-amino-3,5-dichlorophenyl)-2-bromoethanone Chemical compound NC1=C(Cl)C=C(C(=O)CBr)C=C1Cl ATKJJUFAWYSFID-UHFFFAOYSA-N 0.000 description 4
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003254 radicals Chemical group 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- KHEPIAOKCKUGGE-UHFFFAOYSA-N ethanol;hydrochloride Chemical compound Cl.CCO.CCO KHEPIAOKCKUGGE-UHFFFAOYSA-N 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- MGLUCIVJBBOZGS-UHFFFAOYSA-N 1-(4-amino-3,5-dichlorophenyl)-2-[methyl(4-phenylbutan-2-yl)amino]ethanol hydrochloride Chemical compound Cl.NC1=C(C=C(C=C1Cl)C(CN(C(CCC1=CC=CC=C1)C)C)O)Cl MGLUCIVJBBOZGS-UHFFFAOYSA-N 0.000 description 2
- VVFCJVLORNFVHI-UHFFFAOYSA-N 2-(methylamino)-1-phenylethanone Chemical compound CNCC(=O)C1=CC=CC=C1 VVFCJVLORNFVHI-UHFFFAOYSA-N 0.000 description 2
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 description 2
- UHXHHIAYNSRNOI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-methylpropan-1-amine Chemical compound CNCCCC1=CC=C(OC)C=C1 UHXHHIAYNSRNOI-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-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
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 239000011147 inorganic material Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
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- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
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- 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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- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- OKKJLVBELUTLKV-MICDWDOJSA-N deuteriomethanol Chemical compound [2H]CO OKKJLVBELUTLKV-MICDWDOJSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- MBGOAZDBQOWOEA-UHFFFAOYSA-N ethyl N-[2-cyano-6-fluoro-4-[1-hydroxy-2-[3-(4-methoxyphenyl)propylamino]ethyl]phenyl]carbamate Chemical compound C(C)OC(=O)NC1=C(C=C(C=C1F)C(CNCCCC1=CC=C(C=C1)OC)O)C#N MBGOAZDBQOWOEA-UHFFFAOYSA-N 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
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- 238000007912 intraperitoneal administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 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
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
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- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 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
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- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
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- 239000012452 mother liquor Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
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- 229910052763 palladium Inorganic materials 0.000 description 1
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- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
- UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
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- 230000033764 rhythmic process Effects 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000161 steel melt Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- 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
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
- G11B23/00—Record carriers not specific to the method of recording or reproducing; Accessories, e.g. containers, specially adapted for co-operation with the recording or reproducing apparatus ; Intermediate mediums; Apparatus or processes specially adapted for their manufacture
- G11B23/02—Containers; Storing means both adapted to cooperate with the recording or reproducing means
- G11B23/04—Magazines; Cassettes for webs or filaments
- G11B23/08—Magazines; Cassettes for webs or filaments for housing webs or filaments having two distinct ends
- G11B23/087—Magazines; Cassettes for webs or filaments for housing webs or filaments having two distinct ends using two different reels or cores
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
- G11B25/00—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus
- G11B25/06—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus using web-form record carriers, e.g. tape
- G11B25/066—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus using web-form record carriers, e.g. tape adapted for use with containers of different sizes or configurations; adaptor devices therefor
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3046465 | 1980-12-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS229924B2 true CS229924B2 (en) | 1984-07-16 |
Family
ID=6118763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS819178A CS229924B2 (en) | 1980-12-10 | 1981-12-10 | Production method of new phenylalkylamine |
Country Status (32)
| Country | Link |
|---|---|
| JP (1) | JPS57122048A (es) |
| KR (1) | KR870000183B1 (es) |
| AR (1) | AR227802A1 (es) |
| AT (1) | AT379378B (es) |
| AU (1) | AU547655B2 (es) |
| BE (1) | BE891416A (es) |
| CA (1) | CA1202636A (es) |
| CH (1) | CH651541A5 (es) |
| CS (1) | CS229924B2 (es) |
| DD (1) | DD202867A5 (es) |
| DE (1) | DE3146623A1 (es) |
| DK (1) | DK541981A (es) |
| ES (4) | ES507635A0 (es) |
| FI (1) | FI813934L (es) |
| FR (1) | FR2498596B1 (es) |
| GB (1) | GB2088873B (es) |
| GR (1) | GR77323B (es) |
| HU (1) | HU185676B (es) |
| IE (1) | IE52007B1 (es) |
| IL (1) | IL64498A (es) |
| IT (1) | IT1172129B (es) |
| LU (1) | LU83830A1 (es) |
| NL (1) | NL8105170A (es) |
| NO (1) | NO152649C (es) |
| NZ (1) | NZ199215A (es) |
| PH (1) | PH21599A (es) |
| PL (1) | PL129385B1 (es) |
| PT (1) | PT74112B (es) |
| SE (1) | SE8107387L (es) |
| SU (1) | SU1172449A3 (es) |
| YU (1) | YU290381A (es) |
| ZA (1) | ZA818529B (es) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720586A (en) * | 1983-12-06 | 1988-01-19 | Fisons, Plc | Substituted 3,4-dihydroxy-phenylethylamino compounds |
| GB8419963D0 (en) * | 1984-08-06 | 1984-09-12 | Lundbeck & Co As H | Intermediate compound and method |
| GB8426191D0 (en) * | 1984-10-17 | 1984-11-21 | Glaxo Holdings Ltd | Chemical compounds |
| US4943591A (en) * | 1984-10-17 | 1990-07-24 | Glaxo Group Limited | Dichloroaniline derivatives |
| GB8603475D0 (en) * | 1986-02-12 | 1986-03-19 | Glaxo Group Ltd | Chemical compounds |
| GB8703007D0 (en) * | 1987-02-10 | 1987-03-18 | Glaxo Group Ltd | Chemical compounds |
| JPS63290852A (ja) * | 1987-02-10 | 1988-11-28 | グラクソ、グループ、リミテッド | 化合物 |
| US4906645A (en) * | 1988-09-12 | 1990-03-06 | Merck & Co., Inc. | Pyridyl aminoethanol compounds with growth promotion and an increase in feed efficiency |
| DE4028398A1 (de) * | 1990-09-07 | 1992-03-12 | Thomae Gmbh Dr K | Phenylethanolamine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| CA2117250C (en) * | 1991-10-04 | 1999-03-02 | Atsuro Nakazato | Alkoxyphenylalkylamine derivatives |
| US8349898B2 (en) * | 2008-11-18 | 2013-01-08 | Wisconsin Alumni Research Foundation | Sigma-1 receptor ligands and methods of use |
| GB201208775D0 (en) * | 2012-05-18 | 2012-07-04 | Uni I Oslo | Chemical compounds |
| US11999676B2 (en) | 2016-04-21 | 2024-06-04 | University Of Kentucky Research Foundation | Vesicular monoamine transporter-2 ligands and their use in the treatment of psychostimulant abuse |
| US10668030B2 (en) * | 2016-04-21 | 2020-06-02 | University Of Kentucky Research Foundation | Vesicular monoamine transporter-2 ligands and their use in the treatment of psychostimulant abuse |
| WO2023235153A1 (en) * | 2022-05-31 | 2023-12-07 | Corteva Agriscience Llc | Crystalline forms of picolinamide fungicide compound |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1618007A1 (de) * | 1967-05-09 | 1970-10-29 | Thomae Gmbh Dr K | Verfahren zur Herstellung von neuen Amino-monohalogenphenylaethanolaminen |
| DE2351281C3 (de) * | 1973-10-12 | 1981-07-30 | Dr. Karl Thomae Gmbh, 7950 Biberach | Aminophenyl-äthanolamin-Derivate, deren Herstellung und Verwendung |
| NL176168C (nl) * | 1972-12-18 | 1985-03-01 | Thomae Gmbh Dr K | Werkwijze ter bereiding respectievelijk vervaardiging van een farmaceutisch preparaat en werkwijze ter bereiding van daarbij bruikbare nieuwe gesubstitueerde 1-(4-aminofenyl)-2-amino-ethanol-derivaten die, behalve een analgetische, uterusspasmolytische en anti-spastische werking op de dwarsgestreepte spieren, in het bijzonder een beta2-mimetische en/of beta1-blokkerende werking bezitten. |
| JPS51125232A (en) * | 1975-02-05 | 1976-11-01 | Yamanouchi Pharmaceut Co Ltd | Process for preparing 4-substituted amido-3,5-dihalogeno-alpha-substituted aminomethylbenzyl alcohols |
| GB1523974A (en) * | 1975-02-05 | 1978-09-06 | Yamanouchi Pharma Co Ltd | 4-substituted amino- -aminomethylbenzyl alcohol derivatives |
| EP0006961A1 (en) * | 1978-02-21 | 1980-01-23 | Sandoz Ag | New phenylethylamines, process for their preparation, and pharmaceutical compositions containing them |
| DK268579A (da) * | 1978-07-03 | 1980-01-04 | Lilly Co Eli | Fremgangsmaade til fremstilling af phenetamolaminer |
-
1981
- 1981-11-16 NL NL8105170A patent/NL8105170A/nl not_active Application Discontinuation
- 1981-11-25 DE DE19813146623 patent/DE3146623A1/de not_active Withdrawn
- 1981-11-27 SU SU813358171A patent/SU1172449A3/ru active
- 1981-11-30 AT AT0512981A patent/AT379378B/de not_active IP Right Cessation
- 1981-12-02 ES ES507635A patent/ES507635A0/es active Granted
- 1981-12-07 GR GR66712A patent/GR77323B/el unknown
- 1981-12-07 CH CH7800/81A patent/CH651541A5/de not_active IP Right Cessation
- 1981-12-07 IT IT49853/81A patent/IT1172129B/it active
- 1981-12-07 DD DD81235491A patent/DD202867A5/de unknown
- 1981-12-08 DK DK541981A patent/DK541981A/da not_active Application Discontinuation
- 1981-12-08 FI FI813934A patent/FI813934L/fi not_active Application Discontinuation
- 1981-12-09 AU AU78414/81A patent/AU547655B2/en not_active Ceased
- 1981-12-09 JP JP56198337A patent/JPS57122048A/ja active Pending
- 1981-12-09 GB GB8137051A patent/GB2088873B/en not_active Expired
- 1981-12-09 SE SE8107387A patent/SE8107387L/xx not_active Application Discontinuation
- 1981-12-09 IE IE2888/81A patent/IE52007B1/en unknown
- 1981-12-09 PL PL1981234155A patent/PL129385B1/pl unknown
- 1981-12-09 NO NO814194A patent/NO152649C/no unknown
- 1981-12-09 CA CA000391831A patent/CA1202636A/en not_active Expired
- 1981-12-09 IL IL64498A patent/IL64498A/xx unknown
- 1981-12-09 HU HU813708A patent/HU185676B/hu unknown
- 1981-12-09 BE BE0/206788A patent/BE891416A/fr not_active IP Right Cessation
- 1981-12-09 ZA ZA818529A patent/ZA818529B/xx unknown
- 1981-12-09 NZ NZ199215A patent/NZ199215A/en unknown
- 1981-12-10 CS CS819178A patent/CS229924B2/cs unknown
- 1981-12-10 PT PT74112A patent/PT74112B/pt unknown
- 1981-12-10 LU LU83830A patent/LU83830A1/de unknown
- 1981-12-10 YU YU02903/81A patent/YU290381A/xx unknown
- 1981-12-10 FR FR8123106A patent/FR2498596B1/fr not_active Expired
- 1981-12-10 PH PH26726A patent/PH21599A/en unknown
- 1981-12-10 AR AR287754A patent/AR227802A1/es active
- 1981-12-10 KR KR1019810004912A patent/KR870000183B1/ko active IP Right Grant
-
1982
- 1982-06-08 ES ES512914A patent/ES8304537A1/es not_active Expired
- 1982-06-08 ES ES512915A patent/ES8304538A1/es not_active Expired
- 1982-06-08 ES ES512913A patent/ES512913A0/es active Granted
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