GB1574208A - Process for preparing 3-benzazepine derivatives - Google Patents
Process for preparing 3-benzazepine derivatives Download PDFInfo
- Publication number
- GB1574208A GB1574208A GB2066676A GB2066676A GB1574208A GB 1574208 A GB1574208 A GB 1574208A GB 2066676 A GB2066676 A GB 2066676A GB 2066676 A GB2066676 A GB 2066676A GB 1574208 A GB1574208 A GB 1574208A
- Authority
- GB
- United Kingdom
- Prior art keywords
- hydroxy
- acid
- phenyl
- process according
- tetrahydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical class C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 title description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 26
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 18
- -1 7,8 - dimethoxy - 1 - (3 - methoxyphenyl) - 2,3,4,5 - tetrahydro - 1H - 3 benzazepine maleate Chemical compound 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- ZZTAKCGSXKWHAD-UHFFFAOYSA-N 2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-phenylethanol Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=CC=C1 ZZTAKCGSXKWHAD-UHFFFAOYSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- MEXPXLPUVFBQGJ-UHFFFAOYSA-N 5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical class C1NCCC2=CC=CC=C2C1C1=CC=CC=C1 MEXPXLPUVFBQGJ-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- JUDKOGFHZYMDMF-UHFFFAOYSA-N 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol Chemical compound C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1 JUDKOGFHZYMDMF-UHFFFAOYSA-N 0.000 claims description 3
- UKCDAOMGYJOBFT-UHFFFAOYSA-N 2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-(3-methoxyphenyl)ethanol Chemical compound COC1=CC=CC(C(O)CNCCC=2C=C(OC)C(OC)=CC=2)=C1 UKCDAOMGYJOBFT-UHFFFAOYSA-N 0.000 claims description 3
- CBNYARFAQHIUSU-UHFFFAOYSA-N 4-[2-(2-phenylethylamino)ethyl]phenol Chemical compound C1=CC(O)=CC=C1CCNCCC1=CC=CC=C1 CBNYARFAQHIUSU-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 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 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 230000017858 demethylation Effects 0.000 claims description 2
- 238000010520 demethylation reaction Methods 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 16
- 229910052786 argon Inorganic materials 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 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
- 239000003921 oil Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- RTPJBMWUVSTBPC-UHFFFAOYSA-N 2-(2-chlorophenyl)oxirane Chemical compound ClC1=CC=CC=C1C1OC1 RTPJBMWUVSTBPC-UHFFFAOYSA-N 0.000 description 2
- JAIRKHCPVDKYCX-UHFFFAOYSA-N 2-(2-methoxyphenyl)oxirane Chemical compound COC1=CC=CC=C1C1OC1 JAIRKHCPVDKYCX-UHFFFAOYSA-N 0.000 description 2
- AUFMIJGTPFQWAN-UHFFFAOYSA-N 2-(2-methylphenyl)oxirane Chemical compound CC1=CC=CC=C1C1OC1 AUFMIJGTPFQWAN-UHFFFAOYSA-N 0.000 description 2
- YVMKRPGFBQGEBF-UHFFFAOYSA-N 2-(3-chlorophenyl)oxirane Chemical compound ClC1=CC=CC(C2OC2)=C1 YVMKRPGFBQGEBF-UHFFFAOYSA-N 0.000 description 2
- IBWLXNDOMYKTAD-UHFFFAOYSA-N 2-(4-chlorophenyl)oxirane Chemical compound C1=CC(Cl)=CC=C1C1OC1 IBWLXNDOMYKTAD-UHFFFAOYSA-N 0.000 description 2
- ARHIWOBUUAPVTB-UHFFFAOYSA-N 2-(4-methoxyphenyl)oxirane Chemical compound C1=CC(OC)=CC=C1C1OC1 ARHIWOBUUAPVTB-UHFFFAOYSA-N 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 2
- INNWVRBZMBCEJI-UHFFFAOYSA-N 5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1 INNWVRBZMBCEJI-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- YKCAEQUWYQHAPP-UHFFFAOYSA-N n-benzyl-2-(3,4-dimethoxyphenyl)ethanamine Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC1=CC=CC=C1 YKCAEQUWYQHAPP-UHFFFAOYSA-N 0.000 description 2
- ARKSJJPOAHSSQL-UHFFFAOYSA-N 1-(2-bromo-1-methoxyethyl)-3-(trifluoromethyl)benzene Chemical compound COC(CBr)C1=CC=CC(C(F)(F)F)=C1 ARKSJJPOAHSSQL-UHFFFAOYSA-N 0.000 description 1
- JXVGZSPHVKDYJI-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethanol;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=CC=C1Cl JXVGZSPHVKDYJI-UHFFFAOYSA-N 0.000 description 1
- ZWMGYUWAHMIYEA-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethanol;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=CC(Cl)=C1 ZWMGYUWAHMIYEA-UHFFFAOYSA-N 0.000 description 1
- SDCWWENHAIICJY-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethanol;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=C(Cl)C=C1 SDCWWENHAIICJY-UHFFFAOYSA-N 0.000 description 1
- QLSNECRFABDDSX-UHFFFAOYSA-N 1H-1-benzazepin-9-ol Chemical class C1=CC=CNC2=C1C=CC=C2O QLSNECRFABDDSX-UHFFFAOYSA-N 0.000 description 1
- HKJSUKPBCYPOJO-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)ethanamine;hydrobromide Chemical compound Br.COC1=CC=C(CCN)C=C1OC HKJSUKPBCYPOJO-UHFFFAOYSA-N 0.000 description 1
- IJUUWUSPXYGGKY-UHFFFAOYSA-N 2-(3-methoxyphenyl)oxirane Chemical compound COC1=CC=CC(C2OC2)=C1 IJUUWUSPXYGGKY-UHFFFAOYSA-N 0.000 description 1
- HLGUPCNLTKMZDU-UHFFFAOYSA-N 2-(3-methylphenyl)oxirane Chemical compound CC1=CC=CC(C2OC2)=C1 HLGUPCNLTKMZDU-UHFFFAOYSA-N 0.000 description 1
- QAWJAMQTRGCJMH-UHFFFAOYSA-N 2-(4-methylphenyl)oxirane Chemical compound C1=CC(C)=CC=C1C1OC1 QAWJAMQTRGCJMH-UHFFFAOYSA-N 0.000 description 1
- BJWGWTONROZEBR-UHFFFAOYSA-N 2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-(2-methoxyphenyl)ethanol Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=CC=C1OC BJWGWTONROZEBR-UHFFFAOYSA-N 0.000 description 1
- UJRMHKCFHTVNIY-UHFFFAOYSA-N 2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-(3-methylphenyl)ethanol Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)C1=CC=CC(C)=C1 UJRMHKCFHTVNIY-UHFFFAOYSA-N 0.000 description 1
- ARQYVLCQEUBWQV-UHFFFAOYSA-N 2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-(4-methoxyphenyl)ethanol Chemical compound C1=CC(OC)=CC=C1C(O)CNCCC1=CC=C(OC)C(OC)=C1 ARQYVLCQEUBWQV-UHFFFAOYSA-N 0.000 description 1
- VBGNBQHXGIMWTN-UHFFFAOYSA-N 2-[2-(3-methoxyphenyl)ethylamino]-1-phenylethanol Chemical compound COC1=CC=CC(CCNCC(O)C=2C=CC=CC=2)=C1 VBGNBQHXGIMWTN-UHFFFAOYSA-N 0.000 description 1
- PTUWHBLZDQXVTN-UHFFFAOYSA-N 2-[2-(4-methoxyphenyl)ethylamino]-1-phenylethanol Chemical compound C1=CC(OC)=CC=C1CCNCC(O)C1=CC=CC=C1 PTUWHBLZDQXVTN-UHFFFAOYSA-N 0.000 description 1
- PTZWARCWVMSNAD-UHFFFAOYSA-N 2-[benzyl-[2-(3,4-dimethoxyphenyl)ethyl]amino]-1-(3-chlorophenyl)ethanol Chemical compound C1=C(OC)C(OC)=CC=C1CCN(CC=1C=CC=CC=1)CC(O)C1=CC=CC(Cl)=C1 PTZWARCWVMSNAD-UHFFFAOYSA-N 0.000 description 1
- RKNOEAMUSWFZHZ-UHFFFAOYSA-N 2-[benzyl-[2-(3,4-dimethoxyphenyl)ethyl]amino]-1-(4-chlorophenyl)ethanol Chemical compound C1=C(OC)C(OC)=CC=C1CCN(CC=1C=CC=CC=1)CC(O)C1=CC=C(Cl)C=C1 RKNOEAMUSWFZHZ-UHFFFAOYSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 description 1
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WMGIMHQQJMWXBZ-UHFFFAOYSA-N 5-(2-chlorophenyl)-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1Cl WMGIMHQQJMWXBZ-UHFFFAOYSA-N 0.000 description 1
- XSTMOABGZBIBDK-UHFFFAOYSA-N 5-(3-methylphenyl)-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.CC1=CC=CC(C2C3=CC(O)=C(O)C=C3CCNC2)=C1 XSTMOABGZBIBDK-UHFFFAOYSA-N 0.000 description 1
- MJEFZVVUZYTXJT-UHFFFAOYSA-N 5-(4-chlorophenyl)-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=C(Cl)C=C1 MJEFZVVUZYTXJT-UHFFFAOYSA-N 0.000 description 1
- DWNNWSYBUDWPEU-UHFFFAOYSA-N 5-(4-methylphenyl)-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.C1=CC(C)=CC=C1C1C2=CC(O)=C(O)C=C2CCNC1 DWNNWSYBUDWPEU-UHFFFAOYSA-N 0.000 description 1
- WNRDERCTHASHNV-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diol;hydrobromide Chemical compound Br.C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC(C(F)(F)F)=C1 WNRDERCTHASHNV-UHFFFAOYSA-N 0.000 description 1
- JBNFDHZCPYJPNL-UHFFFAOYSA-N 5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepin-6-ol;hydrobromide Chemical compound Br.C1=2C(O)=CC=CC=2CCNCC1C1=CC=CC=C1 JBNFDHZCPYJPNL-UHFFFAOYSA-N 0.000 description 1
- YCCXFCQLRGMHPB-UHFFFAOYSA-N 7,8-dimethoxy-5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1C1=CC=CC=C1 YCCXFCQLRGMHPB-UHFFFAOYSA-N 0.000 description 1
- JHKZEDIOZSNRRC-UHFFFAOYSA-N 7,8-dimethoxy-5-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1C1=CC=CC=C1 JHKZEDIOZSNRRC-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- OGUQCRDMRMUCFR-UHFFFAOYSA-N Br.C=1NC=CC=C2C1C=CC=C2 Chemical compound Br.C=1NC=CC=C2C1C=CC=C2 OGUQCRDMRMUCFR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2066676A GB1574208A (en) | 1976-05-19 | 1976-05-19 | Process for preparing 3-benzazepine derivatives |
| DE19772722043 DE2722043A1 (de) | 1976-05-19 | 1977-05-16 | Verfahren zur herstellung von 1-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepin-derivaten |
| JP5696777A JPS52144686A (en) | 1976-05-19 | 1977-05-16 | Production of 33benzoazepine derivative |
| FR7715361A FR2351967A1 (fr) | 1976-05-19 | 1977-05-18 | Procede de preparation de derives de 3-benzazepines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2066676A GB1574208A (en) | 1976-05-19 | 1976-05-19 | Process for preparing 3-benzazepine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1574208A true GB1574208A (en) | 1980-09-03 |
Family
ID=10149661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB2066676A Expired GB1574208A (en) | 1976-05-19 | 1976-05-19 | Process for preparing 3-benzazepine derivatives |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS52144686A (enExample) |
| DE (1) | DE2722043A1 (enExample) |
| FR (1) | FR2351967A1 (enExample) |
| GB (1) | GB1574208A (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4622342A (en) * | 1981-07-11 | 1986-11-11 | Beecham Group P.L.C. | Secondary amines |
| GB2271566A (en) * | 1992-10-14 | 1994-04-20 | Merck & Co Inc | HIV integrase inhibitors |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5481290A (en) * | 1977-11-17 | 1979-06-28 | Smithkline Corp | Benzazepin compound |
| US5461148A (en) * | 1993-09-27 | 1995-10-24 | Schering Corporation | Process for preparing benzazepine intermediates for the synthesis of D1 antagonists |
| US11525025B2 (en) * | 2018-12-14 | 2022-12-13 | Kraton Polymers Llc | Block copolymers and uses thereof |
-
1976
- 1976-05-19 GB GB2066676A patent/GB1574208A/en not_active Expired
-
1977
- 1977-05-16 DE DE19772722043 patent/DE2722043A1/de not_active Withdrawn
- 1977-05-16 JP JP5696777A patent/JPS52144686A/ja active Pending
- 1977-05-18 FR FR7715361A patent/FR2351967A1/fr active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4622342A (en) * | 1981-07-11 | 1986-11-11 | Beecham Group P.L.C. | Secondary amines |
| GB2271566A (en) * | 1992-10-14 | 1994-04-20 | Merck & Co Inc | HIV integrase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2351967A1 (fr) | 1977-12-16 |
| DE2722043A1 (de) | 1977-12-08 |
| JPS52144686A (en) | 1977-12-02 |
| FR2351967B1 (enExample) | 1980-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100821410B1 (ko) | 4-페닐 치환된 테트라하이드로이소퀴놀린 및 이의치료학적 용도 | |
| US4108989A (en) | 2,3,4,5-tetrahydro-1h-3-benzazepine-7,8-diones | |
| IE46087B1 (en) | Trisubstituted 1-phenyl-2,3,4,5 - tetra-hydro-1h-3-benzazepine compounds | |
| US4011319A (en) | Pharmaceutical compositions and methods involving benzazepine derivatives | |
| LV12630B (en) | 2-aminoindans as selective dopamine d3 ligands | |
| US3403157A (en) | Benzo[6, 7]cyclohepta[1, 2, 3-d, e]isoquinoline derivatives | |
| US4782058A (en) | 1,3,4,6,7,11b-Hexahydro-6-phenyl-2H-pyrazino-(2,1-a)isoquinolines, for anti-histamine or anti-depression treatment | |
| CA1204745A (en) | Hexahydronaphth (1,2-b) -1,4 -oxazines | |
| US20060111385A1 (en) | Novel 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof | |
| CA1240677A (en) | Substituted hexahydro arylquinolizines | |
| CZ51694A3 (en) | Benzoxazine derivatives, process of their preparation and pharmaceutical composition in which said derivatives are comprised | |
| CA1079639A (en) | 3-benzazepine derivatives | |
| GB1574208A (en) | Process for preparing 3-benzazepine derivatives | |
| US4171359A (en) | Benz-tetrasubstituted 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines | |
| US4442126A (en) | 1,2,3,4-Tetrahydronaphthalene derivatives | |
| IL29467A (en) | N-phenyl indoline derivatives | |
| PL136930B1 (en) | Method of obtaining novel derivatives of benzodiazepine | |
| US3225031A (en) | Phenyl-benzazepines and methods for their manufacture | |
| NO162821B (no) | Fremgangsmaate for fremstilling av terapeutisk aktive furo-pyridinderivater. | |
| IE44938B1 (en) | 6,7-benzomorphan derivatives | |
| US4052506A (en) | Pharmaceutical compositions and method of producing anti-parkinsonism activity | |
| PL141501B1 (en) | Method of obtaining novel derivatives of quinoline and indene | |
| US4265889A (en) | 6-Lower alkyl-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines | |
| KR910002564B1 (ko) | 헥사하이드로피롤로[2,1-a]이소퀴놀린 유도체의 제조방법 | |
| EP0033632B1 (en) | 7,8-amino, hydroxy-1-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepines, process for their preparation and pharmaceutical compositions containing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed | ||
| PCNP | Patent ceased through non-payment of renewal fee |