NO812647L - Benzazepinderivater. - Google Patents
Benzazepinderivater.Info
- Publication number
- NO812647L NO812647L NO812647A NO812647A NO812647L NO 812647 L NO812647 L NO 812647L NO 812647 A NO812647 A NO 812647A NO 812647 A NO812647 A NO 812647A NO 812647 L NO812647 L NO 812647L
- Authority
- NO
- Norway
- Prior art keywords
- hydrogen
- group
- lower alkyl
- formula
- alkenyl
- Prior art date
Links
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 title description 10
- 239000001257 hydrogen Substances 0.000 claims description 145
- 229910052739 hydrogen Inorganic materials 0.000 claims description 145
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- 150000001875 compounds Chemical class 0.000 claims description 120
- 150000002431 hydrogen Chemical group 0.000 claims description 92
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
- -1 hydroxymethyl compound Chemical class 0.000 claims description 42
- 125000000304 alkynyl group Chemical group 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 23
- 239000007858 starting material Substances 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- LILHFUJGFBQZPM-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-2,4-dihydropyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=CNC=C2CN=C1C1=CC=CC=C1Cl LILHFUJGFBQZPM-UHFFFAOYSA-N 0.000 claims description 11
- VHNOGETZDZESKL-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-2,4-dihydropyrrolo[3,4-d][2]benzazepine Chemical compound FC1=CC=CC=C1C1=NCC2=CNC=C2C2=CC=C(Cl)C=C12 VHNOGETZDZESKL-UHFFFAOYSA-N 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- BTSGZYKXPCTZMC-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-2-methyl-4h-pyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=CN(C)C=C2CN=C1C1=CC=CC=C1Cl BTSGZYKXPCTZMC-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- 150000004703 alkoxides Chemical class 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 150000002466 imines Chemical group 0.000 claims description 4
- VSDOHBJJRMWLOY-UHFFFAOYSA-N methyl 8-chloro-6-(2-chlorophenyl)-4h-pyrrolo[3,4-d][2]benzazepine-2-carboxylate Chemical compound C12=CC(Cl)=CC=C2C2=CN(C(=O)OC)C=C2CN=C1C1=CC=CC=C1Cl VSDOHBJJRMWLOY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 3
- AGOHXMSGPOYHLT-UHFFFAOYSA-N pyrrolo[3,4-d][2]benzazepine Chemical class N1=CC2=CC=CC=C2C2=CN=CC2=C1 AGOHXMSGPOYHLT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 3
- YYSPSNXIOBATFQ-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-1-methyl-2,4-dihydropyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=C(C)NC=C2CN=C1C1=CC=CC=C1Cl YYSPSNXIOBATFQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 327
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 280
- 239000000203 mixture Substances 0.000 description 142
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 95
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 46
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- 239000007787 solid Substances 0.000 description 39
- 238000001953 recrystallisation Methods 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000000746 purification Methods 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000013078 crystal Substances 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000012280 lithium aluminium hydride Substances 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000012467 final product Substances 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 229940098779 methanesulfonic acid Drugs 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- SMWPBMJVUOELBM-UHFFFAOYSA-N 3-(2-benzoyl-4-chlorophenyl)prop-2-enenitrile Chemical compound ClC1=CC=C(C=CC#N)C(C(=O)C=2C=CC=CC=2)=C1 SMWPBMJVUOELBM-UHFFFAOYSA-N 0.000 description 5
- JSUANPBAYQHQBN-UHFFFAOYSA-N 3-[4-chloro-2-(2-fluorobenzoyl)phenyl]prop-2-enenitrile Chemical compound FC1=CC=CC=C1C(=O)C1=CC(Cl)=CC=C1C=CC#N JSUANPBAYQHQBN-UHFFFAOYSA-N 0.000 description 5
- WIXOADQWUHTLKI-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-1-methyl-2,4-dihydropyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=C(C)NC=C2CN=C1C1=CC=CC=C1F WIXOADQWUHTLKI-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- VMOQUBBQGBNGBD-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-2-methyl-4h-pyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=CN(C)C=C2CN=C1C1=CC=CC=C1F VMOQUBBQGBNGBD-UHFFFAOYSA-N 0.000 description 4
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000002249 anxiolytic agent Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229940117975 chromium trioxide Drugs 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 229910052987 metal hydride Inorganic materials 0.000 description 4
- 150000004681 metal hydrides Chemical class 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- ZUMNVZWXCHVAKW-UHFFFAOYSA-N 2,2,2-trichloro-1-[8-chloro-6-(2-fluorophenyl)-1-methyl-2,4-dihydropyrrolo[3,4-d][2]benzazepin-3-yl]ethanone Chemical compound C12=CC(Cl)=CC=C2C2=C(C)NC(C(=O)C(Cl)(Cl)Cl)=C2CN=C1C1=CC=CC=C1F ZUMNVZWXCHVAKW-UHFFFAOYSA-N 0.000 description 3
- CQSGINBFYDVOOQ-UHFFFAOYSA-N 3-[4-chloro-2-(2-chlorobenzoyl)phenyl]prop-2-enenitrile Chemical compound ClC1=CC=C(C=CC#N)C(C(=O)C=2C(=CC=CC=2)Cl)=C1 CQSGINBFYDVOOQ-UHFFFAOYSA-N 0.000 description 3
- MJBDDUZFQWJYLY-UHFFFAOYSA-N 4-(2-benzoyl-4-chlorophenyl)-1h-pyrrole-3-carbonitrile Chemical compound C=1C=CC=CC=1C(=O)C1=CC(Cl)=CC=C1C1=CNC=C1C#N MJBDDUZFQWJYLY-UHFFFAOYSA-N 0.000 description 3
- ASDAHLYZLZIMRB-UHFFFAOYSA-N 4-[4-chloro-2-(2-fluorobenzoyl)phenyl]-1h-pyrrole-3-carbonitrile Chemical compound FC1=CC=CC=C1C(=O)C1=CC(Cl)=CC=C1C1=CNC=C1C#N ASDAHLYZLZIMRB-UHFFFAOYSA-N 0.000 description 3
- ZISHUIMSWPBOSO-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-2,4-dihydropyrrolo[3,4-d][2]benzazepine-3-carbaldehyde Chemical compound C12=CC(Cl)=CC=C2C2=CNC(C=O)=C2CN=C1C1=CC=CC=C1Cl ZISHUIMSWPBOSO-UHFFFAOYSA-N 0.000 description 3
- XPTWRNPCTUBIMY-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-2,4-dihydropyrrolo[3,4-d][2]benzazepine-3-carboxylic acid Chemical compound OC(=O)C=1NC=C(C2=CC=C(Cl)C=C22)C=1CN=C2C1=CC=CC=C1Cl XPTWRNPCTUBIMY-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- CUMYCBZGJLFFQC-UHFFFAOYSA-N (8-chloro-6-phenyl-2,4-dihydropyrrolo[3,4-d][2]benzazepin-1-yl)methanol Chemical compound C12=CC(Cl)=CC=C2C2=C(CO)NC=C2CN=C1C1=CC=CC=C1 CUMYCBZGJLFFQC-UHFFFAOYSA-N 0.000 description 2
- NGOUPILQFWOEET-UHFFFAOYSA-N 1-(1-isocyanoethylsulfonyl)-4-methylbenzene Chemical compound [C-]#[N+]C(C)S(=O)(=O)C1=CC=C(C)C=C1 NGOUPILQFWOEET-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- RLKDAQKJMRBCEU-UHFFFAOYSA-N 1h-1-benzazepine-3-carbaldehyde Chemical compound C1=CC(C=O)=CNC2=CC=CC=C21 RLKDAQKJMRBCEU-UHFFFAOYSA-N 0.000 description 2
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 2
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- KWGZQBGZDZDGCU-UHFFFAOYSA-N [2-[3-(aminomethyl)-5-prop-2-enyl-1,2-dihydropyrrol-3-yl]-5-chlorophenyl]-(2-fluorophenyl)methanol Chemical compound C=1C=C(Cl)C=C(C(O)C=2C(=CC=CC=2)F)C=1C1(CN)CNC(CC=C)=C1 KWGZQBGZDZDGCU-UHFFFAOYSA-N 0.000 description 1
- LMGIXQZNOPHFTH-UHFFFAOYSA-N [2-[4-(aminomethyl)-2-methyl-1h-pyrrol-3-yl]-5-chlorophenyl]-(2-fluorophenyl)methanol Chemical compound N1C=C(CN)C(C=2C(=CC(Cl)=CC=2)C(O)C=2C(=CC=CC=2)F)=C1C LMGIXQZNOPHFTH-UHFFFAOYSA-N 0.000 description 1
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 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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- 229910052794 bromium Inorganic materials 0.000 description 1
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- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 description 1
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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- PLKKXWBJOVTVEU-UHFFFAOYSA-N pyrrolo[2,3-i][1]benzazepine Chemical class C1=CC=NC2=C3C=CN=C3C=CC2=C1 PLKKXWBJOVTVEU-UHFFFAOYSA-N 0.000 description 1
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- 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 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
- C07C45/305—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation with halogenochromate reagents, e.g. pyridinium chlorochromate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
- C07C63/68—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings containing halogen
- C07C63/72—Polycyclic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17555580A | 1980-08-05 | 1980-08-05 | |
| US06/286,124 US4354973A (en) | 1980-08-05 | 1981-07-23 | Pyrrolo[3,4-d][2]benzazepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO812647L true NO812647L (no) | 1982-02-08 |
Family
ID=26871324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO812647A NO812647L (no) | 1980-08-05 | 1981-08-04 | Benzazepinderivater. |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4354973A (es) |
| EP (1) | EP0045519B1 (es) |
| AR (1) | AR230639A1 (es) |
| AT (1) | ATE13888T1 (es) |
| AU (1) | AU545298B2 (es) |
| CA (1) | CA1174674A (es) |
| CH (1) | CH648849A5 (es) |
| DE (2) | DE3171021D1 (es) |
| DK (1) | DK347681A (es) |
| ES (4) | ES8300765A1 (es) |
| FI (1) | FI71149C (es) |
| FR (1) | FR2488257A1 (es) |
| GB (1) | GB2083460B (es) |
| HU (1) | HU188071B (es) |
| IE (1) | IE51466B1 (es) |
| IL (1) | IL63487A (es) |
| IT (1) | IT1138133B (es) |
| LU (1) | LU83531A1 (es) |
| MC (1) | MC1409A1 (es) |
| NL (1) | NL8103655A (es) |
| NO (1) | NO812647L (es) |
| NZ (1) | NZ197920A (es) |
| PH (1) | PH16814A (es) |
| PT (1) | PT73481B (es) |
| SE (1) | SE8104659L (es) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3372369D1 (de) * | 1982-05-18 | 1987-08-13 | Hoffmann La Roche | Pyrrole (3,4-d)(2)benzazepine derivatives |
| US4436662A (en) | 1982-06-28 | 1984-03-13 | Hoffmann-La Roche Inc. | Pyrrolo[3,4-d][2]benzazepinones |
| US5098901A (en) * | 1991-09-10 | 1992-03-24 | Sterling Drug Inc. | Imidazo [1,2-b][2]benzazepine and pyrimido [1,2-b][2]benzazepine antiarrhythmic agents |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3523947A (en) * | 1966-11-23 | 1970-08-11 | Hoffmann La Roche | 1-cyclic amidine-5-aryl-1,4-benzodiazepine and process |
| US3947585A (en) * | 1974-06-03 | 1976-03-30 | Ciba-Geigy Corporation | Pyrazolobenzazepines |
| US4022801A (en) * | 1974-06-03 | 1977-05-10 | Ciba-Geigy Corporation | Pyrazolobenzazepines |
| US4169150A (en) * | 1975-11-12 | 1979-09-25 | Teijin Limited | Benzodiazepine derivatives and pharmaceutical compositions containing said derivatives |
-
1981
- 1981-07-23 US US06/286,124 patent/US4354973A/en not_active Expired - Fee Related
- 1981-07-27 CH CH4869/81A patent/CH648849A5/de not_active IP Right Cessation
- 1981-08-03 SE SE8104659A patent/SE8104659L/xx unknown
- 1981-08-03 NL NL8103655A patent/NL8103655A/nl not_active Application Discontinuation
- 1981-08-03 LU LU83531A patent/LU83531A1/de unknown
- 1981-08-03 IL IL63487A patent/IL63487A/xx unknown
- 1981-08-03 IT IT23347/81A patent/IT1138133B/it active
- 1981-08-03 NZ NZ197920A patent/NZ197920A/en unknown
- 1981-08-03 HU HU812247A patent/HU188071B/hu unknown
- 1981-08-04 MC MC811533A patent/MC1409A1/xx unknown
- 1981-08-04 FI FI812416A patent/FI71149C/fi not_active IP Right Cessation
- 1981-08-04 NO NO812647A patent/NO812647L/no unknown
- 1981-08-04 PH PH26000A patent/PH16814A/en unknown
- 1981-08-04 GB GB8123763A patent/GB2083460B/en not_active Expired
- 1981-08-04 FR FR8115107A patent/FR2488257A1/fr active Granted
- 1981-08-04 PT PT73481A patent/PT73481B/pt unknown
- 1981-08-04 ES ES504525A patent/ES8300765A1/es not_active Expired
- 1981-08-04 DK DK347681A patent/DK347681A/da not_active Application Discontinuation
- 1981-08-04 CA CA000383108A patent/CA1174674A/en not_active Expired
- 1981-08-05 DE DE8181106137T patent/DE3171021D1/de not_active Expired
- 1981-08-05 DE DE19813131064 patent/DE3131064A1/de not_active Withdrawn
- 1981-08-05 EP EP81106137A patent/EP0045519B1/de not_active Expired
- 1981-08-05 AR AR286350A patent/AR230639A1/es active
- 1981-08-05 AT AT81106137T patent/ATE13888T1/de not_active IP Right Cessation
- 1981-08-05 AU AU73825/81A patent/AU545298B2/en not_active Ceased
- 1981-08-14 IE IE1775/81A patent/IE51466B1/en unknown
-
1982
- 1982-07-01 ES ES513620A patent/ES513620A0/es active Granted
- 1982-07-01 ES ES513621A patent/ES513621A0/es active Granted
- 1982-07-01 ES ES513622A patent/ES513622A0/es active Granted
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