NZ197920A - 8-halo-6-phenyl-2h,4h-pyrrolo(3,4-d)(2)-benzazepines - Google Patents
8-halo-6-phenyl-2h,4h-pyrrolo(3,4-d)(2)-benzazepinesInfo
- Publication number
- NZ197920A NZ197920A NZ197920A NZ19792081A NZ197920A NZ 197920 A NZ197920 A NZ 197920A NZ 197920 A NZ197920 A NZ 197920A NZ 19792081 A NZ19792081 A NZ 19792081A NZ 197920 A NZ197920 A NZ 197920A
- Authority
- NZ
- New Zealand
- Prior art keywords
- hydrogen
- lower alkyl
- formula
- group
- alkynyl
- Prior art date
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 180
- 239000001257 hydrogen Substances 0.000 claims description 169
- 229910052739 hydrogen Inorganic materials 0.000 claims description 169
- 150000001875 compounds Chemical class 0.000 claims description 167
- 150000002431 hydrogen Chemical class 0.000 claims description 112
- 125000003342 alkenyl group Chemical group 0.000 claims description 99
- 125000000304 alkynyl group Chemical group 0.000 claims description 97
- -1 C^ to C_ Chemical group 0.000 claims description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 23
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 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 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 150000004703 alkoxides Chemical class 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 239000002249 anxiolytic agent Substances 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 6
- 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 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
- 230000002152 alkylating effect Effects 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
- 239000011707 mineral Substances 0.000 claims description 5
- 239000000932 sedative agent Substances 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000005518 carboxamido group Chemical group 0.000 claims description 4
- 150000001735 carboxylic acids Chemical class 0.000 claims description 4
- 150000002466 imines Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 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 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 230000000949 anxiolytic effect Effects 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 230000001624 sedative effect Effects 0.000 claims description 3
- 125000001424 substituent group Chemical group 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
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 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 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 229940125723 sedative agent Drugs 0.000 claims description 2
- RVMFVFNTEFQYCF-UHFFFAOYSA-N 2-[8-chloro-6-(2-fluorophenyl)-4h-pyrrolo[3,4-d][2]benzazepin-2-yl]ethanol Chemical compound C12=CC(Cl)=CC=C2C2=CN(CCO)C=C2CN=C1C1=CC=CC=C1F RVMFVFNTEFQYCF-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 229940005530 anxiolytics Drugs 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 303
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 277
- 239000000203 mixture Substances 0.000 description 140
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 106
- 239000000243 solution Substances 0.000 description 96
- 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 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 45
- 239000007787 solid Substances 0.000 description 39
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
- 238000001953 recrystallisation Methods 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000000746 purification Methods 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000003480 eluent Substances 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- XUUSYXJGMRQBKQ-UHFFFAOYSA-N 2h-2-benzazepine Chemical compound N1C=CC=C2C=CC=CC2=C1 XUUSYXJGMRQBKQ-UHFFFAOYSA-N 0.000 description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 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
- 238000004440 column chromatography Methods 0.000 description 13
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
- 239000012280 lithium aluminium hydride Substances 0.000 description 12
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 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
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 229940098779 methanesulfonic acid Drugs 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000003826 tablet 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 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 6
- 230000000694 effects Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 125000005843 halogen group Chemical group 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
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 230000001376 precipitating effect Effects 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 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
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
- 238000004587 chromatography analysis Methods 0.000 description 4
- 229960004132 diethyl ether Drugs 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
- 150000004702 methyl esters Chemical class 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 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
- 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 3
- ZKXFBTJZHZYVJW-UHFFFAOYSA-N 8-chloro-6-phenyl-2,4-dihydropyrrolo[3,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=CNC=C2CN=C1C1=CC=CC=C1 ZKXFBTJZHZYVJW-UHFFFAOYSA-N 0.000 description 3
- SYAHIHKAZUTIDI-UHFFFAOYSA-N C1=NC=C2CNC=C3C(=C21)C=CC=C3 Chemical compound C1=NC=C2CNC=C3C(=C21)C=CC=C3 SYAHIHKAZUTIDI-UHFFFAOYSA-N 0.000 description 3
- CPYSUUSFGSKRSD-UHFFFAOYSA-N Cl.Cl.C=1NC=CC=C2C1C=CC=C2 Chemical compound Cl.Cl.C=1NC=CC=C2C1C=CC=C2 CPYSUUSFGSKRSD-UHFFFAOYSA-N 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 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
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
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- OFSVXQSEYSHGQO-UHFFFAOYSA-N methyl 8-chloro-6-(2-chlorophenyl)-5-oxido-4h-pyrrolo[3,4-d][2]benzazepin-5-ium-2-carboxylate Chemical compound C12=CC(Cl)=CC=C2C2=CN(C(=O)OC)C=C2C[N+]([O-])=C1C1=CC=CC=C1Cl OFSVXQSEYSHGQO-UHFFFAOYSA-N 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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
- AGOHXMSGPOYHLT-UHFFFAOYSA-N pyrrolo[3,4-d][2]benzazepine Chemical class N1=CC2=CC=CC=C2C2=CN=CC2=C1 AGOHXMSGPOYHLT-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 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
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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 |
|---|---|
| NZ197920A true NZ197920A (en) | 1984-11-09 |
Family
ID=26871324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ197920A NZ197920A (en) | 1980-08-05 | 1981-08-03 | 8-halo-6-phenyl-2h,4h-pyrrolo(3,4-d)(2)-benzazepines |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4354973A (enExample) |
| EP (1) | EP0045519B1 (enExample) |
| AR (1) | AR230639A1 (enExample) |
| AT (1) | ATE13888T1 (enExample) |
| AU (1) | AU545298B2 (enExample) |
| CA (1) | CA1174674A (enExample) |
| CH (1) | CH648849A5 (enExample) |
| DE (2) | DE3171021D1 (enExample) |
| DK (1) | DK347681A (enExample) |
| ES (4) | ES504525A0 (enExample) |
| FI (1) | FI71149C (enExample) |
| FR (1) | FR2488257A1 (enExample) |
| GB (1) | GB2083460B (enExample) |
| HU (1) | HU188071B (enExample) |
| IE (1) | IE51466B1 (enExample) |
| IL (1) | IL63487A (enExample) |
| IT (1) | IT1138133B (enExample) |
| LU (1) | LU83531A1 (enExample) |
| MC (1) | MC1409A1 (enExample) |
| NL (1) | NL8103655A (enExample) |
| NO (1) | NO812647L (enExample) |
| NZ (1) | NZ197920A (enExample) |
| PH (1) | PH16814A (enExample) |
| PT (1) | PT73481B (enExample) |
| SE (1) | SE8104659L (enExample) |
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 NZ NZ197920A patent/NZ197920A/en unknown
- 1981-08-03 SE SE8104659A patent/SE8104659L/xx unknown
- 1981-08-03 IT IT23347/81A patent/IT1138133B/it active
- 1981-08-03 HU HU812247A patent/HU188071B/hu unknown
- 1981-08-03 LU LU83531A patent/LU83531A1/de unknown
- 1981-08-03 IL IL63487A patent/IL63487A/xx unknown
- 1981-08-03 NL NL8103655A patent/NL8103655A/nl not_active Application Discontinuation
- 1981-08-04 FI FI812416A patent/FI71149C/fi not_active IP Right Cessation
- 1981-08-04 PH PH26000A patent/PH16814A/en unknown
- 1981-08-04 PT PT73481A patent/PT73481B/pt unknown
- 1981-08-04 ES ES504525A patent/ES504525A0/es active Granted
- 1981-08-04 FR FR8115107A patent/FR2488257A1/fr active Granted
- 1981-08-04 DK DK347681A patent/DK347681A/da not_active Application Discontinuation
- 1981-08-04 CA CA000383108A patent/CA1174674A/en not_active Expired
- 1981-08-04 MC MC811533A patent/MC1409A1/fr unknown
- 1981-08-04 NO NO812647A patent/NO812647L/no unknown
- 1981-08-04 GB GB8123763A patent/GB2083460B/en not_active Expired
- 1981-08-05 AT AT81106137T patent/ATE13888T1/de not_active IP Right Cessation
- 1981-08-05 AR AR286350A patent/AR230639A1/es active
- 1981-08-05 EP EP81106137A patent/EP0045519B1/de 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 AU AU73825/81A patent/AU545298B2/en not_active Ceased
- 1981-08-14 IE IE1775/81A patent/IE51466B1/en unknown
-
1982
- 1982-07-01 ES ES513621A patent/ES513621A0/es active Granted
- 1982-07-01 ES ES513622A patent/ES513622A0/es active Granted
- 1982-07-01 ES ES513620A patent/ES8304983A1/es not_active Expired
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