CA1207764A - Process for preparation of benzazepine derivatives - Google Patents

Process for preparation of benzazepine derivatives

Info

Publication number: CA1207764A
Authority: CA; Canada
Prior art keywords: group; ethyl; methyl; amino; dimethoxy
Prior art date: 1982-11-16
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

Application number

CA000441311A

Other languages

English (en)

French (fr)

Inventor

Manfred Reiffen

Norbert Hauel

Wolfgang Eberlein

Christian Lillie

Helmut Pieper

Joachim Heider

Volkhard Austel

Walter Kobinger

Klaus Noll

Gerd Kruger

Johannes Keck

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Boehringer Ingelheim Pharma GmbH and Co KG

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1982-11-16

Filing date

1983-11-16

Publication date

1986-07-15

1983-11-16 Application filed by Individual filed Critical Individual

1986-07-15 Application granted granted Critical

1986-07-15 Publication of CA1207764A publication Critical patent/CA1207764A/en

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 25
238000002360 preparation method Methods 0.000 title claims abstract description 4
150000008038 benzoazepines Chemical class 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 20
229910001927 ruthenium tetroxide Inorganic materials 0.000 claims abstract description 11
230000003647 oxidation Effects 0.000 claims abstract description 6
238000007254 oxidation reaction Methods 0.000 claims abstract description 6
238000007363 ring formation reaction Methods 0.000 claims abstract description 4
-1 methylenedioxy group Chemical group 0.000 claims description 45
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 23
125000000217 alkyl group Chemical group 0.000 claims description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 18
239000002904 solvent Substances 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 12
239000001294 propane Substances 0.000 claims description 12
159000000000 sodium salts Chemical class 0.000 claims description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
239000000460 chlorine Chemical group 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 10
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 7
239000005977 Ethylene Substances 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 7
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 7
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical class N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
238000011065 in-situ storage Methods 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
150000007524 organic acids Chemical class 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
238000010992 reflux Methods 0.000 claims description 5
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
239000008096 xylene Substances 0.000 claims description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
239000007789 gas Substances 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
235000005985 organic acids Nutrition 0.000 claims description 4
239000011541 reaction mixture Substances 0.000 claims description 4
235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Chemical group 0.000 claims description 3
238000005984 hydrogenation reaction Methods 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
125000004806 1-methylethylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims description 2
WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 claims description 2
238000009833 condensation Methods 0.000 claims description 2
230000005494 condensation Effects 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
AZLDAUCSPMSDQH-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)ethyl]-3-(7,8-dimethoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-n-methylpropan-1-amine Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCN1CCC2=CC(OC)=C(OC)C=C2CC1 AZLDAUCSPMSDQH-UHFFFAOYSA-N 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 15
238000010438 heat treatment Methods 0.000 claims 9
WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 claims 6
KEDQCFRVSHYKLR-UHFFFAOYSA-N 3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 KEDQCFRVSHYKLR-UHFFFAOYSA-N 0.000 claims 4
230000001590 oxidative effect Effects 0.000 claims 4
HAWADECOVOAPBV-UHFFFAOYSA-N 3-[3-[2-(4-amino-3,5-dichlorophenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound O=C1CC=2C=C(OC)C(OC)=CC=2CCN1CCCN(C)CCC1=CC(Cl)=C(N)C(Cl)=C1 HAWADECOVOAPBV-UHFFFAOYSA-N 0.000 claims 3
YNZRMJASGPITFJ-UHFFFAOYSA-N 7,8-dimethoxy-3-[3-[2-(4-methoxyphenyl)ethyl-methylamino]propyl]-2,5-dihydro-1h-3-benzazepin-4-one Chemical compound C1=CC(OC)=CC=C1CCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 YNZRMJASGPITFJ-UHFFFAOYSA-N 0.000 claims 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims 2
MFTAYOFCMBHZDR-UHFFFAOYSA-N 2,6-dichloro-4-[2-(methylamino)ethyl]aniline Chemical compound CNCCC1=CC(Cl)=C(N)C(Cl)=C1 MFTAYOFCMBHZDR-UHFFFAOYSA-N 0.000 claims 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
125000001309 chloro group Chemical group Cl* 0.000 claims 1
238000006482 condensation reaction Methods 0.000 claims 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims 1
125000006250 trifluoro ethyl amino group Chemical group [H]N(*)C([H])([H])C(F)(F)F 0.000 claims 1
230000000144 pharmacologic effect Effects 0.000 abstract description 2
230000001603 reducing effect Effects 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
238000002844 melting Methods 0.000 description 14
230000008018 melting Effects 0.000 description 14
229940073584 methylene chloride Drugs 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229960003390 magnesium sulfate Drugs 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
125000005977 3-phenylpropyloxy group Chemical group 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
229960001701 chloroform Drugs 0.000 description 2
238000001816 cooling Methods 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
239000007858 starting material Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
BBGYASXSZUVYLQ-UHFFFAOYSA-N 1-nitro-2-[(2-nitrophenoxy)-phenylphosphoryl]oxybenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1OP(=O)(C=1C=CC=CC=1)OC1=CC=CC=C1[N+]([O-])=O BBGYASXSZUVYLQ-UHFFFAOYSA-N 0.000 description 1
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
HQWDKLAIDBOLFE-UHFFFAOYSA-M 2-fluoro-1-methylpyridin-1-ium;4-methylbenzenesulfonate Chemical compound C[N+]1=CC=CC=C1F.CC1=CC=C(S([O-])(=O)=O)C=C1 HQWDKLAIDBOLFE-UHFFFAOYSA-M 0.000 description 1
125000004807 2-methylethylene group Chemical group [H]C([H])([H])C([H])([*:2])C([H])([H])[*:1] 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
JPVUTECGMCLYRL-UHFFFAOYSA-N 2h-3-benzazepine Chemical compound C1=NCC=C2C=CC=CC2=C1 JPVUTECGMCLYRL-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
YAFZZBASNSJRSP-UHFFFAOYSA-N 5,5-dimethoxy-1,2,3,4-tetrahydro-3-benzazepine Chemical compound COC1(OC)CNCCC2=CC=CC=C12 YAFZZBASNSJRSP-UHFFFAOYSA-N 0.000 description 1
RXKTVGMZJMDNLF-UHFFFAOYSA-N 7,8-dimethoxy-1,2,3,5-tetrahydro-3-benzazepin-4-one Chemical compound C1CNC(=O)CC2=C1C=C(OC)C(OC)=C2 RXKTVGMZJMDNLF-UHFFFAOYSA-N 0.000 description 1
VDGMXVIYNQRPOH-UHFFFAOYSA-N C=1C=CC=CC=1P(C=1C=CC=CC=1)(OCC(F)(F)F)C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(OCC(F)(F)F)C1=CC=CC=C1 VDGMXVIYNQRPOH-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
239000002585 base Substances 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
238000004061 bleaching Methods 0.000 description 1
238000009835 boiling Methods 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000007265 chloromethylation reaction Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
FGEKTVAHFDQHBU-UHFFFAOYSA-N dioxoruthenium;hydrate Chemical compound O.O=[Ru]=O FGEKTVAHFDQHBU-UHFFFAOYSA-N 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000006629 isopropoxycarbonylamino group Chemical group 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000155 melt Substances 0.000 description 1
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
150000002825 nitriles Chemical group 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000007970 thio esters Chemical group 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
- C07D233/08—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms
- C07D233/12—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D233/16—Radicals substituted by nitrogen atoms
- 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)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

CA000441311A 1982-11-16 1983-11-16 Process for preparation of benzazepine derivatives Expired CA1207764A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DEP3242345.4		1982-11-16
DE19823242345 DE3242345A1 (de)	1982-11-16	1982-11-16	Verfahren zur herstellung von benzazepinderivaten

Publications (1)

Publication Number	Publication Date
CA1207764A true CA1207764A (en)	1986-07-15

Family

ID=6178258

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000441311A Expired CA1207764A (en)	1982-11-16	1983-11-16	Process for preparation of benzazepine derivatives

Country Status (12)

Country	Link
KR (1)	KR900006325B1 (da)
AT (1)	AT389509B (da)
CA (1)	CA1207764A (da)
DD (1)	DD215541A5 (da)
DE (1)	DE3242345A1 (da)
DK (1)	DK155666C (da)
ES (2)	ES527270A0 (da)
FI (1)	FI77234C (da)
GR (1)	GR79427B (da)
HU (1)	HU190918B (da)
NO (1)	NO168244C (da)
PT (1)	PT77676B (da)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3474090A (en) *	1966-12-22	1969-10-21	American Cyanamid Co	3-aminoalkyl-1,3-benzodiazepin-2-ones
US3780023A (en) *	1972-06-30	1973-12-18	J Suh	2-aralkylamino-4,5-dihydro-3h-1,3-benzodiazepines
US4210749A (en) *	1974-11-12	1980-07-01	Pennwalt Corporation	Substituted 1,2,4,5-tetrahydro-3H,3 benzazepines
DE2639718C2 (de) *	1976-09-03	1987-03-05	Dr. Karl Thomae Gmbh, 7950 Biberach	1-[6,7-Dimethoxy-3,4-dihydro-2H-isochinolin-1-on-2-yl]-3-[N-methyl-N-(2-(3,4-dimethoxy-phenyl)-äthyl)-amino]-propan, dessen physiologisch verträgliche Säureadditionssalze und diese Verbindungen enthaltende Arzneimittel

1982
- 1982-11-16 DE DE19823242345 patent/DE3242345A1/de not_active Withdrawn
1983
- 1983-10-12 AT AT0363283A patent/AT389509B/de not_active IP Right Cessation
- 1983-11-09 GR GR72933A patent/GR79427B/el unknown
- 1983-11-10 FI FI834121A patent/FI77234C/fi not_active IP Right Cessation
- 1983-11-14 DK DK519983A patent/DK155666C/da not_active IP Right Cessation
- 1983-11-14 DD DD83256668A patent/DD215541A5/de not_active IP Right Cessation
- 1983-11-15 PT PT77676A patent/PT77676B/pt unknown
- 1983-11-15 ES ES527270A patent/ES527270A0/es active Granted
- 1983-11-15 NO NO834176A patent/NO168244C/no not_active IP Right Cessation
- 1983-11-15 HU HU833932A patent/HU190918B/hu unknown
- 1983-11-16 CA CA000441311A patent/CA1207764A/en not_active Expired
- 1983-11-16 KR KR1019830005432A patent/KR900006325B1/ko not_active Expired
1984
- 1984-05-17 ES ES532551A patent/ES532551A0/es active Granted

Also Published As

Publication number	Publication date
DE3242345A1 (de)	1984-05-17
ES8502425A1 (es)	1985-01-01
DK519983A (da)	1984-05-17
DD215541A5 (de)	1984-11-14
NO834176L (no)	1984-05-18
NO168244B (no)	1991-10-21
KR900006325B1 (ko)	1990-08-28
ES8502975A1 (es)	1985-02-01
PT77676A (de)	1983-12-01
HU190918B (en)	1986-12-28
DK155666B (da)	1989-05-01
FI77234B (fi)	1988-10-31
FI77234C (fi)	1989-02-10
ATA363283A (de)	1989-05-15
KR840006627A (ko)	1984-12-01
NO168244C (no)	1992-01-29
DK519983D0 (da)	1983-11-14
ES532551A0 (es)	1985-02-01
FI834121A0 (fi)	1983-11-10
GR79427B (da)	1984-10-22
FI834121A7 (fi)	1984-05-17
AT389509B (de)	1989-12-27
PT77676B (pt)	1986-05-12
ES527270A0 (es)	1985-01-01
DK155666C (da)	1989-09-04

Legal Events

Date	Code	Title	Description
2003-11-16	MKEX	Expiry

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