NO834222L - Analogifremgangsmaate for fremstilling av terapeutisk aktive benzazepinderivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive benzazepinderivaterInfo
- Publication number
- NO834222L NO834222L NO834222A NO834222A NO834222L NO 834222 L NO834222 L NO 834222L NO 834222 A NO834222 A NO 834222A NO 834222 A NO834222 A NO 834222A NO 834222 L NO834222 L NO 834222L
- Authority
- NO
- Norway
- Prior art keywords
- group
- carbon atoms
- general formula
- compound
- amino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 33
- 150000008038 benzoazepines Chemical class 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 239000002253 acid Substances 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- -1 methoxy-phenyl Chemical group 0.000 claims description 135
- 125000004432 carbon atom Chemical group C* 0.000 claims description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 30
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 28
- 239000000460 chlorine Substances 0.000 claims description 28
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
- 125000002947 alkylene group Chemical group 0.000 claims description 25
- 239000011737 fluorine Substances 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 230000001681 protective effect Effects 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 230000000269 nucleophilic effect Effects 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 235000005985 organic acids Nutrition 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- JGUTYLDGJJHFBT-UHFFFAOYSA-N 3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-5-hydroxy-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCN1C(=O)C(O)C2=CC(OC)=C(OC)C=C2CC1 JGUTYLDGJJHFBT-UHFFFAOYSA-N 0.000 claims description 3
- JOJYPPPEXXKIAB-UHFFFAOYSA-N 3-[3-[2-(4-amino-3-nitrophenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCC1=CC=C(N)C([N+]([O-])=O)=C1 JOJYPPPEXXKIAB-UHFFFAOYSA-N 0.000 claims description 3
- VCOUWOAFZOWUEA-UHFFFAOYSA-N 3-[3-[3-(4-amino-3,5-dichlorophenyl)propyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCCC1=CC(Cl)=C(N)C(Cl)=C1 VCOUWOAFZOWUEA-UHFFFAOYSA-N 0.000 claims description 3
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 229910001927 ruthenium tetroxide Inorganic materials 0.000 claims description 3
- YRLKEKWJRPBWQO-UHFFFAOYSA-N 3-[3-[3-(3,4-dimethoxyphenyl)propyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CCCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 YRLKEKWJRPBWQO-UHFFFAOYSA-N 0.000 claims description 2
- YBJNIZQQTNSSJG-UHFFFAOYSA-N 7,8-dimethoxy-3-[3-[methyl(2-phenylethyl)amino]propyl]-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCC1=CC=CC=C1 YBJNIZQQTNSSJG-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 4
- 125000006524 alkoxy alkyl amino group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 238000002844 melting Methods 0.000 description 32
- 230000008018 melting Effects 0.000 description 32
- 239000002904 solvent Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000003480 eluent Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000002329 infrared spectrum Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 239000001294 propane Substances 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000012279 sodium borohydride Substances 0.000 description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 239000011877 solvent mixture Substances 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940093915 gynecological organic acid Drugs 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229910052987 metal hydride Inorganic materials 0.000 description 5
- 150000004681 metal hydrides Chemical class 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000002211 ultraviolet spectrum Methods 0.000 description 5
- YKOKLDUFMABJCV-UHFFFAOYSA-N 3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-1,2-dihydro-3-benzazepine-4,5-dione Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCN1C(=O)C(=O)C2=CC(OC)=C(OC)C=C2CC1 YKOKLDUFMABJCV-UHFFFAOYSA-N 0.000 description 4
- PFKLMOLPKCFSKQ-UHFFFAOYSA-N 3-[3-[3-(3,4-dimethoxyphenyl)propyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 PFKLMOLPKCFSKQ-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- GYIYVTGAOWHWRI-UHFFFAOYSA-N 1,2,3,5-tetrahydro-3-benzazepin-4-one Chemical compound C1CNC(=O)CC2=CC=CC=C21 GYIYVTGAOWHWRI-UHFFFAOYSA-N 0.000 description 3
- ODEZTTCXWTUAJT-UHFFFAOYSA-N 3-(3-chloropropyl)-7,8-dimethoxy-1h-3-benzazepin-2-one Chemical compound C1C(=O)N(CCCCl)C=CC2=C1C=C(OC)C(OC)=C2 ODEZTTCXWTUAJT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 150000007530 organic bases Chemical group 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- HNJWKRMESUMDQE-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-methylethanamine Chemical compound CNCCC1=CC=C(OC)C(OC)=C1 HNJWKRMESUMDQE-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 2
- UKLLLQWDPVQNPO-UHFFFAOYSA-N 3-(3-chloropropyl)-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1CN(CCCCl)C(=O)CC2=C1C=C(OC)C(OC)=C2 UKLLLQWDPVQNPO-UHFFFAOYSA-N 0.000 description 2
- GFYSZRAGHMXPFY-UHFFFAOYSA-N 3-[3-[4-[4-(dimethylamino)phenyl]butyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one;hydrobromide Chemical compound Br.O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCCCC1=CC=C(N(C)C)C=C1 GFYSZRAGHMXPFY-UHFFFAOYSA-N 0.000 description 2
- LFHQGSWUEFPJJC-UHFFFAOYSA-N 3-[3-[5-(3,4-dimethoxyphenyl)pentyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCCCCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 LFHQGSWUEFPJJC-UHFFFAOYSA-N 0.000 description 2
- GBBMIHDXFRQORR-UHFFFAOYSA-N 3-[3-[[2-(3,4-dimethoxyphenyl)-2-hydroxyethyl]-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1C(O)CN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 GBBMIHDXFRQORR-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- MYKGTRBNDHJLMO-UHFFFAOYSA-N 7,8-dimethoxy-3-[3-[methyl(2-phenylethyl)amino]propyl]-2,5-dihydro-1h-3-benzazepin-4-one;dihydrochloride Chemical compound Cl.Cl.O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCC1=CC=CC=C1 MYKGTRBNDHJLMO-UHFFFAOYSA-N 0.000 description 2
- WUNQZFYRIABBKP-UHFFFAOYSA-N 7-methoxy-1,2,3,5-tetrahydro-3-benzazepin-4-one Chemical compound C1CNC(=O)CC2=CC(OC)=CC=C21 WUNQZFYRIABBKP-UHFFFAOYSA-N 0.000 description 2
- ZQIYRIXYCQWHON-UHFFFAOYSA-N 8-bromo-3-(3-chloropropyl)-7-methoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1C(=O)N(CCCCl)CCC2=C1C=C(OC)C(Br)=C2 ZQIYRIXYCQWHON-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
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- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
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- 229910001622 calcium bromide Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
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- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
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- 238000004042 decolorization Methods 0.000 description 1
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- WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
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- 238000001990 intravenous administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 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
- 239000000155 melt Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
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- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
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- 229960001412 pentobarbital Drugs 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- SDQCGKJCBWXRMK-UHFFFAOYSA-N propan-2-yl 4-methylbenzenesulfonate Chemical compound CC(C)OS(=O)(=O)C1=CC=C(C)C=C1 SDQCGKJCBWXRMK-UHFFFAOYSA-N 0.000 description 1
- UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Luminescent Compositions (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823242599 DE3242599A1 (de) | 1982-11-18 | 1982-11-18 | Neue benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO834222L true NO834222L (no) | 1984-05-21 |
Family
ID=6178417
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO834222A NO834222L (no) | 1982-11-18 | 1983-11-17 | Analogifremgangsmaate for fremstilling av terapeutisk aktive benzazepinderivater |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0109636B1 (es) |
| JP (1) | JPS59106466A (es) |
| KR (1) | KR840006628A (es) |
| AT (1) | ATE40118T1 (es) |
| AU (1) | AU568101B2 (es) |
| CA (1) | CA1211107A (es) |
| CS (1) | CS239947B2 (es) |
| DD (1) | DD215540A5 (es) |
| DE (2) | DE3242599A1 (es) |
| DK (1) | DK527483A (es) |
| ES (2) | ES527308A0 (es) |
| FI (1) | FI834174A (es) |
| GB (1) | GB2130213B (es) |
| GR (1) | GR81253B (es) |
| HU (1) | HU193189B (es) |
| IE (1) | IE56261B1 (es) |
| IL (1) | IL70258A (es) |
| NO (1) | NO834222L (es) |
| NZ (1) | NZ206305A (es) |
| PL (1) | PL139449B1 (es) |
| PT (1) | PT77683B (es) |
| YU (1) | YU226283A (es) |
| ZA (1) | ZA838572B (es) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3418271A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3631013A1 (de) * | 1986-09-12 | 1988-03-24 | Thomae Gmbh Dr K | Neue naphthylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| JP2699511B2 (ja) * | 1988-01-29 | 1998-01-19 | 武田薬品工業株式会社 | 置換アミン類 |
| FR2868776B1 (fr) * | 2004-04-13 | 2008-04-18 | Servier Lab | Nouveau procede de synthese de derives de la 1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3474090A (en) * | 1966-12-22 | 1969-10-21 | American Cyanamid Co | 3-aminoalkyl-1,3-benzodiazepin-2-ones |
| US3780023A (en) * | 1972-06-30 | 1973-12-18 | J Suh | 2-aralkylamino-4,5-dihydro-3h-1,3-benzodiazepines |
| US4210749A (en) * | 1974-11-12 | 1980-07-01 | Pennwalt Corporation | Substituted 1,2,4,5-tetrahydro-3H,3 benzazepines |
| DE2639718A1 (de) * | 1976-09-03 | 1978-03-16 | Thomae Gmbh Dr K | Neue phenylaethylamine |
| IN156096B (es) * | 1981-03-19 | 1985-05-11 | Usv Pharma Corp | |
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3269625D1 (en) * | 1981-08-11 | 1986-04-10 | Ciba Geigy Ag | Benzazepin-2-ones, process for their preparation, pharmaceutical preparations containing these compounds and the compounds for therapeutical use |
| JPS6436829A (en) * | 1987-07-31 | 1989-02-07 | Shinko Kinzoku Kogyo Kk | Evacuation part washing apparatus |
-
1982
- 1982-11-18 DE DE19823242599 patent/DE3242599A1/de not_active Withdrawn
-
1983
- 1983-11-14 EP EP83111348A patent/EP0109636B1/de not_active Expired
- 1983-11-14 DE DE8383111348T patent/DE3378980D1/de not_active Expired
- 1983-11-14 AT AT83111348T patent/ATE40118T1/de not_active IP Right Cessation
- 1983-11-15 CS CS838456A patent/CS239947B2/cs unknown
- 1983-11-15 FI FI834174A patent/FI834174A/fi not_active Application Discontinuation
- 1983-11-16 ES ES527308A patent/ES527308A0/es active Granted
- 1983-11-16 GR GR73003A patent/GR81253B/el unknown
- 1983-11-16 DD DD83256756A patent/DD215540A5/de unknown
- 1983-11-17 NO NO834222A patent/NO834222L/no unknown
- 1983-11-17 JP JP58217069A patent/JPS59106466A/ja active Granted
- 1983-11-17 GB GB08330731A patent/GB2130213B/en not_active Expired
- 1983-11-17 AU AU21461/83A patent/AU568101B2/en not_active Ceased
- 1983-11-17 IL IL70258A patent/IL70258A/xx not_active IP Right Cessation
- 1983-11-17 NZ NZ206305A patent/NZ206305A/en unknown
- 1983-11-17 YU YU02262/83A patent/YU226283A/xx unknown
- 1983-11-17 CA CA000441425A patent/CA1211107A/en not_active Expired
- 1983-11-17 PT PT77683A patent/PT77683B/pt unknown
- 1983-11-17 IE IE2692/83A patent/IE56261B1/en not_active IP Right Cessation
- 1983-11-17 PL PL1983244610A patent/PL139449B1/pl unknown
- 1983-11-17 DK DK527483A patent/DK527483A/da not_active Application Discontinuation
- 1983-11-17 HU HU833968A patent/HU193189B/hu unknown
- 1983-11-17 ZA ZA838572A patent/ZA838572B/xx unknown
- 1983-11-18 KR KR1019830005495A patent/KR840006628A/ko not_active Application Discontinuation
-
1984
- 1984-05-21 ES ES532662A patent/ES8502689A1/es not_active Expired
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