FI78473C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1-fenyloxi-2,3,4,5-tetrahydro-3-bensazepinderivat, och vid foerfarandet anvaendbara mellanprodukter. - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1-fenyloxi-2,3,4,5-tetrahydro-3-bensazepinderivat, och vid foerfarandet anvaendbara mellanprodukter. Download PDFInfo
- Publication number
- FI78473C FI78473C FI832092A FI832092A FI78473C FI 78473 C FI78473 C FI 78473C FI 832092 A FI832092 A FI 832092A FI 832092 A FI832092 A FI 832092A FI 78473 C FI78473 C FI 78473C
- Authority
- FI
- Finland
- Prior art keywords
- tetrahydro
- benzazepine
- formula
- alkyl
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 48
- 238000002360 preparation method Methods 0.000 title claims description 7
- YPSCVOIRZZGNDZ-UHFFFAOYSA-N 5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical class C1NCCC2=CC=CC=C2C1OC1=CC=CC=C1 YPSCVOIRZZGNDZ-UHFFFAOYSA-N 0.000 title description 4
- 239000000543 intermediate Substances 0.000 title description 4
- -1 alkylene amine Chemical class 0.000 claims abstract description 55
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 25
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 23
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 21
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical group 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 84
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 8
- 150000004820 halides Chemical class 0.000 claims description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
- 239000000935 antidepressant agent Substances 0.000 claims description 5
- 229940005513 antidepressants Drugs 0.000 claims description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000000202 analgesic effect Effects 0.000 claims description 4
- 230000001430 anti-depressive effect Effects 0.000 claims description 4
- 230000003276 anti-hypertensive effect Effects 0.000 claims description 4
- MAIIKQNCBVQRBM-UHFFFAOYSA-N 7,8-dimethoxy-5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC=C1 MAIIKQNCBVQRBM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000007344 nucleophilic reaction Methods 0.000 claims description 3
- CAOMJAMNASENBC-UHFFFAOYSA-N 7,8-dimethoxy-5-[4-(trifluoromethyl)phenoxy]-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(C(F)(F)F)C=C1 CAOMJAMNASENBC-UHFFFAOYSA-N 0.000 claims description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 229910052796 boron Inorganic materials 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- ZMOPIHQDPJYYKW-UHFFFAOYSA-N 5-(3-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC(Cl)=C1 ZMOPIHQDPJYYKW-UHFFFAOYSA-N 0.000 claims 1
- VOIFXRDZAJDFPB-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC=CC=C2CCNC1 VOIFXRDZAJDFPB-UHFFFAOYSA-N 0.000 claims 1
- AOHFDDOIDVKIPT-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(C(F)(F)F)C=C1 AOHFDDOIDVKIPT-UHFFFAOYSA-N 0.000 claims 1
- ZUGSPVVYXXJHCM-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=CC=C1 ZUGSPVVYXXJHCM-UHFFFAOYSA-N 0.000 claims 1
- WNBKEEWOYWFAIT-UHFFFAOYSA-N 7,8-dimethoxy-5-(4-methoxyphenoxy)-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC(OC)=C(OC)C=C2CCN(C)C1 WNBKEEWOYWFAIT-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000000243 solution Substances 0.000 description 221
- 239000003921 oil Substances 0.000 description 156
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 145
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 144
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 63
- 238000004458 analytical method Methods 0.000 description 60
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 53
- 239000011541 reaction mixture Substances 0.000 description 52
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000463 material Substances 0.000 description 30
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 29
- 239000000725 suspension Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 229910010082 LiAlH Inorganic materials 0.000 description 18
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 16
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- 150000003891 oxalate salts Chemical class 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 230000037396 body weight Effects 0.000 description 11
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- RXPDDRVCOCIHMI-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepin-5-ol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(O)C2=CC=CC=C2CC1 RXPDDRVCOCIHMI-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 8
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000004533 oil dispersion Substances 0.000 description 8
- 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 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 7
- 150000002688 maleic acid derivatives Chemical class 0.000 description 7
- YNLHBGLBJHVNTK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepin-5-ol Chemical compound OC1CNCCC2=CC=CC=C12 YNLHBGLBJHVNTK-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- FLSBQILUUNXTLC-UHFFFAOYSA-N 5-(3-chlorophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound ClC1=CC=CC(OC2C3=CC=CC=C3CCNC2)=C1 FLSBQILUUNXTLC-UHFFFAOYSA-N 0.000 description 5
- JEJAWQBUJIIGHW-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenoxy]-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCNC1 JEJAWQBUJIIGHW-UHFFFAOYSA-N 0.000 description 5
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 5
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
- 239000008098 formaldehyde solution Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- RJCGZNCCVKIBHO-UHFFFAOYSA-N 1-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1 RJCGZNCCVKIBHO-UHFFFAOYSA-N 0.000 description 3
- UNNNAIWPDLRVRN-UHFFFAOYSA-N 1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1 UNNNAIWPDLRVRN-UHFFFAOYSA-N 0.000 description 3
- LUIGKSPQPMWPBD-UHFFFAOYSA-N 2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]acetonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCN(CC#N)C1 LUIGKSPQPMWPBD-UHFFFAOYSA-N 0.000 description 3
- FMWXHMHXIQZWQP-UHFFFAOYSA-N 2-phenyl-1-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanone Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCN(C(=O)CC=2C=CC=CC=2)C1 FMWXHMHXIQZWQP-UHFFFAOYSA-N 0.000 description 3
- OTHVHPXQXPEEEN-UHFFFAOYSA-N 3-methyl-5-(4-methylphenoxy)-1,2,4,5-tetrahydro-3-benzazepine;hydrobromide Chemical compound Br.C1N(C)CCC2=CC=CC=C2C1OC1=CC=C(C)C=C1 OTHVHPXQXPEEEN-UHFFFAOYSA-N 0.000 description 3
- DNXJMKZXHNYVLQ-UHFFFAOYSA-N 5-(3-chlorophenoxy)-3-(2-phenylethyl)-1,2,4,5-tetrahydro-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.ClC1=CC=CC(OC2C3=CC=CC=C3CCN(CCC=3C=CC=CC=3)C2)=C1 DNXJMKZXHNYVLQ-UHFFFAOYSA-N 0.000 description 3
- LZTGRANIEAXJAB-UHFFFAOYSA-N 5-(3-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC(Cl)=C1 LZTGRANIEAXJAB-UHFFFAOYSA-N 0.000 description 3
- CELRYVDTFOSENW-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine;hydrochloride Chemical compound Cl.C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(C(F)(F)F)C=C1 CELRYVDTFOSENW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- HXXNUJBODGEODL-UHFFFAOYSA-N N-methyl-2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanamine oxalic acid Chemical compound C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.CNCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 HXXNUJBODGEODL-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- IMORGMGAXWQYDB-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate Chemical compound C1N(C(=O)OCC)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 IMORGMGAXWQYDB-UHFFFAOYSA-N 0.000 description 3
- SSOFTMBPQFNSRI-UHFFFAOYSA-N ethyl n-[2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethyl]carbamate Chemical compound C1N(CCNC(=O)OCC)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 SSOFTMBPQFNSRI-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
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- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38791682 | 1982-06-14 | ||
| US06/387,916 US4988690A (en) | 1982-06-14 | 1982-06-14 | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines and anti-depressant use thereof |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI832092A0 FI832092A0 (fi) | 1983-06-10 |
| FI832092L FI832092L (fi) | 1983-12-15 |
| FI78473B FI78473B (fi) | 1989-04-28 |
| FI78473C true FI78473C (fi) | 1989-08-10 |
Family
ID=23531838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI832092A FI78473C (fi) | 1982-06-14 | 1983-06-10 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1-fenyloxi-2,3,4,5-tetrahydro-3-bensazepinderivat, och vid foerfarandet anvaendbara mellanprodukter. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4988690A (en:Method) |
| EP (1) | EP0096838B1 (en:Method) |
| JP (1) | JPS595165A (en:Method) |
| KR (1) | KR900001214B1 (en:Method) |
| AT (1) | ATE26263T1 (en:Method) |
| AU (1) | AU570920B2 (en:Method) |
| CA (1) | CA1214460A (en:Method) |
| DE (1) | DE3370621D1 (en:Method) |
| DK (1) | DK270983A (en:Method) |
| ES (1) | ES8503666A1 (en:Method) |
| FI (1) | FI78473C (en:Method) |
| GR (1) | GR78291B (en:Method) |
| HU (1) | HU190902B (en:Method) |
| IE (1) | IE55404B1 (en:Method) |
| IL (1) | IL68964A (en:Method) |
| PT (1) | PT76864B (en:Method) |
| ZA (1) | ZA834309B (en:Method) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH27337A (en) * | 1987-03-27 | 1993-06-08 | Schering Corp | Substituted benzazepines their preparation and pharmaceutical compositions containing them |
| US5015639A (en) * | 1987-03-27 | 1991-05-14 | Schering Corporation | Substituted benzazepines, their preparation and pharmaceutical compositions containing them |
| CA1327795C (en) * | 1987-08-14 | 1994-03-15 | Jules Freedman | Antidepressants which are aryloxy inadanamines |
| US5202319A (en) * | 1991-09-23 | 1993-04-13 | Hoechst-Roussel Pharmaceuticals Inc. | Substituted 3-amino-2,3,4,5-tetrahydro-1-aryloxy-3-benzazepines |
| US5639482A (en) * | 1993-11-10 | 1997-06-17 | Crary; Ely J. | Composition for control and prevention of diabetic retinopathy |
| US7115766B2 (en) * | 2000-11-30 | 2006-10-03 | Indiana University Research & Technology Corp. | Nucleophilic approach for preparing radiolabeled imaging agents and associated compounds |
| US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| NZ578503A (en) * | 2003-06-17 | 2011-02-25 | Arena Pharm Inc | Benzazepine derivatives useful for the treatment of 5HT2C receptor associated diseases |
| EP2332921B1 (en) | 2003-06-17 | 2016-03-02 | Arena Pharmaceuticals, Inc. | 8-Chloro-1 -methyl-2,3,4,5-tetrahydro-1 H-3benzazapine Hydrochloride |
| WO2005042491A1 (en) * | 2003-10-22 | 2005-05-12 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases |
| US20070275949A1 (en) * | 2003-10-22 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2C Receptor Associated Diseases |
| CN101084193B (zh) | 2004-12-21 | 2011-12-07 | 艾尼纳制药公司 | (r)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓盐酸盐的晶型 |
| AU2005322183B2 (en) | 2004-12-23 | 2012-03-29 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulator compositions and methods of use |
| JP5199997B2 (ja) | 2006-04-03 | 2013-05-15 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ８−クロロ−１−メチル−２，３，４，５−テトラヒドロ−１ｈ−３−ベンズアゼピンおよびこれに関連する中間体を調製するためのプロセス |
| ES2522587T3 (es) * | 2006-12-05 | 2014-11-17 | Arena Pharmaceuticals, Inc. | Procesos para preparar (R)-8-cloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzacepina e intermedios de la misma |
| NZ580802A (en) | 2007-05-10 | 2012-09-28 | Albany Molecular Res Inc | Aryloxy-and heteroaryloxy-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| JP5491421B2 (ja) | 2008-03-04 | 2014-05-14 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ５−ｈｔ２ｃアゴニストである（ｒ）−８−クロロ−１−メチル−２，３，４，５−テトラヒドロ−１ｈ−３−ベンゾアゼピンに関連する中間体の調製のためのプロセス |
| EP2443080A2 (en) | 2009-06-18 | 2012-04-25 | Arena Pharmaceuticals, Inc. | Process for the preparation of 5-ht2c receptor agonists |
| KR20130112848A (ko) | 2010-06-02 | 2013-10-14 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 수용체 아고니스트의 제조 방법 |
| KR20130101524A (ko) | 2010-09-01 | 2013-09-13 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 아고니스트의 비-흡습성 염 |
| NZ608266A (en) | 2010-09-01 | 2015-09-25 | Arena Pharm Inc | Administration of lorcaserin to individuals with renal impairment |
| CA2808909A1 (en) | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Salts of lorcaserin with optically active acids |
| CA2808912C (en) | 2010-09-01 | 2019-09-17 | Zezhi Jesse Shao | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
| KR20150070249A (ko) | 2012-10-09 | 2015-06-24 | 아레나 파마슈티칼스, 인크. | 체중 관리 방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5233687A (en) * | 1975-09-11 | 1977-03-14 | Shionogi & Co Ltd | Process for preparation of 1,5-dihydro-2h-1,4-benzodiazepine-2-on deri vatives |
| JPS5481290A (en) * | 1977-11-17 | 1979-06-28 | Smithkline Corp | Benzazepin compound |
-
1982
- 1982-06-14 US US06/387,916 patent/US4988690A/en not_active Expired - Fee Related
-
1983
- 1983-06-08 AT AT83105610T patent/ATE26263T1/de not_active IP Right Cessation
- 1983-06-08 EP EP83105610A patent/EP0096838B1/en not_active Expired
- 1983-06-08 DE DE8383105610T patent/DE3370621D1/de not_active Expired
- 1983-06-10 FI FI832092A patent/FI78473C/fi not_active IP Right Cessation
- 1983-06-11 KR KR1019830002597A patent/KR900001214B1/ko not_active Expired
- 1983-06-13 GR GR71648A patent/GR78291B/el unknown
- 1983-06-13 ES ES523191A patent/ES8503666A1/es not_active Expired
- 1983-06-13 DK DK270983A patent/DK270983A/da not_active Application Discontinuation
- 1983-06-13 ZA ZA834309A patent/ZA834309B/xx unknown
- 1983-06-13 CA CA000430280A patent/CA1214460A/en not_active Expired
- 1983-06-13 IE IE1384/83A patent/IE55404B1/en unknown
- 1983-06-13 JP JP58104343A patent/JPS595165A/ja active Granted
- 1983-06-13 HU HU832096A patent/HU190902B/hu not_active IP Right Cessation
- 1983-06-13 IL IL68964A patent/IL68964A/xx unknown
- 1983-06-14 PT PT76864A patent/PT76864B/pt unknown
- 1983-06-14 AU AU15764/83A patent/AU570920B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| KR900001214B1 (ko) | 1990-02-28 |
| HU190902B (en) | 1986-12-28 |
| ATE26263T1 (de) | 1987-04-15 |
| CA1214460A (en) | 1986-11-25 |
| DK270983A (da) | 1983-12-15 |
| FI832092A0 (fi) | 1983-06-10 |
| US4988690A (en) | 1991-01-29 |
| AU570920B2 (en) | 1988-03-31 |
| JPH0365342B2 (en:Method) | 1991-10-11 |
| ES523191A0 (es) | 1985-03-01 |
| IE831384L (en) | 1983-12-14 |
| PT76864A (en) | 1983-07-01 |
| IL68964A0 (en) | 1983-10-31 |
| IL68964A (en) | 1988-03-31 |
| GR78291B (en:Method) | 1984-09-26 |
| JPS595165A (ja) | 1984-01-12 |
| FI78473B (fi) | 1989-04-28 |
| ZA834309B (en) | 1984-03-28 |
| AU1576483A (en) | 1983-12-22 |
| KR840005103A (ko) | 1984-11-03 |
| FI832092L (fi) | 1983-12-15 |
| DE3370621D1 (en) | 1987-05-07 |
| ES8503666A1 (es) | 1985-03-01 |
| DK270983D0 (da) | 1983-06-13 |
| IE55404B1 (en) | 1990-09-12 |
| PT76864B (en) | 1986-02-27 |
| EP0096838A1 (en) | 1983-12-28 |
| EP0096838B1 (en) | 1987-04-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED |