DD147355A5 - Verfahren zur herstellung von merkapto-substituierten 2,3,4,5-tetrahydro-1h-3-benzazepinen - Google Patents

Verfahren zur herstellung von merkapto-substituierten 2,3,4,5-tetrahydro-1h-3-benzazepinen Download PDF

Info

Publication number: DD147355A5
Authority: DD; German Democratic Republic
Prior art keywords: compound; benzazepine; tetrahydro; methyl; solution
Prior art date: 1978-07-07

Application number

DD79214179A

Other languages

German (de)

English (en)

Inventor

Kenneth G Holden

Carl Kaiser

Original Assignee

Smithkline Corp

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.)

1978-07-07

Filing date

1979-07-06

Publication date

1981-04-01

1979-07-06 Application filed by Smithkline Corp filed Critical Smithkline Corp

1981-04-01 Publication of DD147355A5 publication Critical patent/DD147355A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 28
238000004519 manufacturing process Methods 0.000 title description 2
-1 mercapto-substituted 2,3,4,5-tetrahydro-1H-3-benzazepines Chemical class 0.000 claims abstract description 59
150000001875 compounds Chemical class 0.000 claims abstract description 51
150000003839 salts Chemical class 0.000 claims abstract description 24
239000002253 acid Substances 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
238000002360 preparation method Methods 0.000 claims abstract description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 12
229910052794 bromium Inorganic materials 0.000 claims abstract description 12
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 11
231100000252 nontoxic Toxicity 0.000 claims abstract description 11
230000003000 nontoxic effect Effects 0.000 claims abstract description 11
125000004423 acyloxy group Chemical group 0.000 claims abstract description 9
125000001589 carboacyl group Chemical group 0.000 claims abstract description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
125000001424 substituent group Chemical group 0.000 claims abstract description 6
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
125000002541 furyl group Chemical group 0.000 claims abstract description 4
125000001544 thienyl group Chemical group 0.000 claims abstract description 4
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims abstract description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
239000011737 fluorine Substances 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 2
101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 50
238000006243 chemical reaction Methods 0.000 claims description 22
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 11
GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 claims description 10
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
230000017858 demethylation Effects 0.000 claims description 5
238000010520 demethylation reaction Methods 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
238000006193 diazotization reaction Methods 0.000 claims description 3
235000019253 formic acid Nutrition 0.000 claims description 3
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
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 claims description 2
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 claims description 2
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 2
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
230000001335 demethylating effect Effects 0.000 claims 2
102000015554 Dopamine receptor Human genes 0.000 abstract description 5
108050004812 Dopamine receptor Proteins 0.000 abstract description 5
230000003474 anti-emetic effect Effects 0.000 abstract description 5
239000002111 antiemetic agent Substances 0.000 abstract description 4
230000003472 neutralizing effect Effects 0.000 abstract description 4
229940125683 antiemetic agent Drugs 0.000 abstract description 2
239000000164 antipsychotic agent Substances 0.000 abstract description 2
229940005529 antipsychotics Drugs 0.000 abstract description 2
239000003814 drug Substances 0.000 abstract description 2
101100072620 Streptomyces griseus ind2 gene Proteins 0.000 abstract 1
239000000243 solution Substances 0.000 description 129
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
239000000203 mixture Substances 0.000 description 67
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
238000002844 melting Methods 0.000 description 39
230000008018 melting Effects 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
239000000284 extract Substances 0.000 description 23
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 17
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
239000005457 ice water Substances 0.000 description 16
238000003756 stirring Methods 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
239000007787 solid Substances 0.000 description 14
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
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 9
239000012954 diazonium Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000000908 ammonium hydroxide Substances 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000012458 free base Substances 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
239000012259 ether extract Substances 0.000 description 7
229930182817 methionine Natural products 0.000 description 7
235000006109 methionine Nutrition 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
238000010992 reflux Methods 0.000 description 7
235000010288 sodium nitrite Nutrition 0.000 description 7
YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 6
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 6
239000012362 glacial acetic acid Substances 0.000 description 6
239000010410 layer Substances 0.000 description 6
229940098779 methanesulfonic acid Drugs 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 6
MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
229940005561 1,4-benzoquinone Drugs 0.000 description 4
MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical class N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 description 4
OWWDHUYMZNCYQA-UHFFFAOYSA-N 7,8-dimethoxy-6-phenylsulfanyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound COC=1C(OC)=CC=2CCNCCC=2C=1SC1=CC=CC=C1 OWWDHUYMZNCYQA-UHFFFAOYSA-N 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 4
WIVXEZIMDUGYRW-UHFFFAOYSA-L copper(i) sulfate Chemical compound [Cu+].[Cu+].[O-]S([O-])(=O)=O WIVXEZIMDUGYRW-UHFFFAOYSA-L 0.000 description 4
238000001035 drying Methods 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
CPKAMNTVOIXDAP-UHFFFAOYSA-N 6-chloro-3-methyl-9-nitro-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1CN(C)CCC2=C(Cl)C=CC([N+]([O-])=O)=C21 CPKAMNTVOIXDAP-UHFFFAOYSA-N 0.000 description 3
MHKDOURMQPZPAG-UHFFFAOYSA-N 7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=C1C=C(OC)C(OC)=C2 MHKDOURMQPZPAG-UHFFFAOYSA-N 0.000 description 3
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
238000010171 animal model Methods 0.000 description 3
150000008038 benzoazepines Chemical class 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000002775 capsule Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
229940045803 cuprous chloride Drugs 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
150000001989 diazonium salts Chemical class 0.000 description 3
239000002895 emetic Substances 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
238000002156 mixing Methods 0.000 description 3
229910017604 nitric acid Inorganic materials 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
MYOAKAGSEUSIMT-UHFFFAOYSA-N 1h-3-benzazepine Chemical compound C1C=NC=CC2=CC=CC=C12 MYOAKAGSEUSIMT-UHFFFAOYSA-N 0.000 description 2
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 2
WSSWXGZEJNNFSN-UHFFFAOYSA-N 2,3-dihydro-1h-1-benzazepine Chemical compound N1CCC=CC2=CC=CC=C21 WSSWXGZEJNNFSN-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
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JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
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KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
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239000003085 diluting agent Substances 0.000 description 1
LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
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239000012467 final product Substances 0.000 description 1
239000008098 formaldehyde solution Substances 0.000 description 1
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
239000003517 fume Substances 0.000 description 1
CMDKYFGIJALPLS-UHFFFAOYSA-N furan-2-thiol Chemical compound SC1=CC=CO1 CMDKYFGIJALPLS-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
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LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical class COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
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WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
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238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
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239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
VBBHYFZIAZEXOY-UHFFFAOYSA-N n-(6-chloro-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-9-yl)acetamide Chemical compound C1CN(C)CCC2=C(Cl)C=CC(NC(C)=O)=C21 VBBHYFZIAZEXOY-UHFFFAOYSA-N 0.000 description 1
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238000007254 oxidation reaction Methods 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000003825 pressing Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
229910001958 silver carbonate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
GCZQHDFWKVMZOE-UHFFFAOYSA-N thiophen-2-ylmethanethiol Chemical compound SCC1=CC=CS1 GCZQHDFWKVMZOE-UHFFFAOYSA-N 0.000 description 1
VSGXHZUTTFLSBC-UHFFFAOYSA-N thiophene-3-thiol Chemical compound SC=1C=CSC=1 VSGXHZUTTFLSBC-UHFFFAOYSA-N 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure 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
- 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
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Anesthesiology (AREA)
Neurology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Other In-Based Heterocyclic Compounds (AREA)

DD79214179A 1978-07-07 1979-07-06 Verfahren zur herstellung von merkapto-substituierten 2,3,4,5-tetrahydro-1h-3-benzazepinen DD147355A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US92261378A	1978-07-07	1978-07-07

Publications (1)

Publication Number	Publication Date
DD147355A5 true DD147355A5 (de)	1981-04-01

Family

ID=25447325

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD79214179A DD147355A5 (de)	1978-07-07	1979-07-06	Verfahren zur herstellung von merkapto-substituierten 2,3,4,5-tetrahydro-1h-3-benzazepinen

Country Status (24)

Country	Link
EP (2)	EP0080012B1 (da)
JP (1)	JPS5511584A (da)
AR (1)	AR222828A1 (da)
AU (1)	AU525789B2 (da)
CA (1)	CA1115271A (da)
CS (1)	CS213381B2 (da)
DD (1)	DD147355A5 (da)
DE (1)	DE2964530D1 (da)
DK (1)	DK156001C (da)
ES (3)	ES482276A1 (da)
FI (1)	FI67215C (da)
GR (1)	GR69675B (da)
HU (1)	HU179315B (da)
IE (1)	IE48654B1 (da)
IL (1)	IL57532A (da)
IT (1)	IT1193190B (da)
JO (1)	JO1273B1 (da)
NO (1)	NO152213C (da)
NZ (1)	NZ190745A (da)
PH (1)	PH15754A (da)
PL (1)	PL216908A1 (da)
PT (1)	PT69855A (da)
SU (1)	SU1029827A3 (da)
ZA (1)	ZA792785B (da)

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DE3119874A1 (de)	1981-05-19	1982-12-09	Dr. Karl Thomae Gmbh, 7950 Biberach	"benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel"
US4469634A (en) *	1982-07-29	1984-09-04	Smithkline Beckman Corporation	Allyloxy- and allylthio-2,3,4,5-tetrahydro-1H-3-benzazepines
US4652642A (en) *	1984-08-23	1987-03-24	Smithkline Beckman Corporation	Azidobenzazepines
US4683229A (en) *	1986-03-17	1987-07-28	Smithkline Beckman Corporation	6-halo-9-alkenyleneoxy-3-alkyl-2,3,4,5-tetrahydro-(1H-3)-benzazepines and their use as selective alpha-adrenergic receptor antagonists
US6384079B1 (en)	1986-12-23	2002-05-07	Tristrata Technology, Incorporated	Compositions comprising 2-hydroxycarboxylic acids and related compounds, and methods for alleviating signs of dermatological aging
US5942250A (en) *	1986-12-23	1999-08-24	Tristrata Technology, Inc.	Compositions and methods for enhancing the topical effects of sunscreen agents
GB9119467D0 (en) *	1991-09-12	1991-10-23	Smithkline Beecham Corp	Chemical compounds
GB9708805D0 (en)	1997-05-01	1997-06-25	Smithkline Beecham Plc	Compounds
GB9810876D0 (en)	1998-05-20	1998-07-22	Smithkline Beecham Plc	Compounds
SK4782001A3 (en) *	1998-10-08	2001-11-06	Smithkline Beecham Plc	Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)
US6953787B2 (en)	2002-04-12	2005-10-11	Arena Pharmaceuticals, Inc.	5HT2C receptor modulators
ES2264003T3 (es)	2002-10-07	2006-12-16	Glaxo Group Limited	Derivados de sulfonamida como agentges antipsicoticos.
MXPA05013364A (es)	2003-06-17	2006-03-17	Arena Pharm Inc	Procedimiento para preparar 3-benzazepinas.
US7704993B2 (en)	2003-06-17	2010-04-27	Arena Pharmaceuticals, Inc.	Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases
EA011011B1 (ru) *	2004-02-25	2008-12-30	Эли Лилли Энд Компани	6-ЗАМЕЩЁННЫЕ 2,3,4,5-ТЕТРАГИДРО-1H-БЕНЗО[d]АЗЕПИНЫ В КАЧЕСТВЕ АГОНИСТОВ РЕЦЕПТОРОВ 5-HT
BRPI0519726B8 (pt)	2004-12-21	2021-05-25	Arena Pharm Inc	composto de hemidrato de (r)-8-cloro-1-metil-2,3,4,5-tetraidro-1h-3-benzazepina, composição compreendendo o referido composto e seus usos
BRPI0515862A2 (pt)	2004-12-23	2011-10-11	Arena Pharm Inc	uso de fentermina e agonista seletivo do receptor de 5ht-2c na preparação de composições, composições moduladoras do receptor de 5ht-2c e forma de dosagem unitária compreendendo as mesmas
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
JP5404414B2 (ja)	2006-12-05	2014-01-29	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	（ｒ）−８−クロロ−１−メチル−２，３，４，５−テトラヒドロ−１ｈ−３−ベンゾアゼピンおよびその中間体を調製するための方法
US8822727B2 (en)	2008-03-04	2014-09-02	Arena Pharmaceuticals, Inc.	Processes for the preparation of intermediates related to the 5-HT2C agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
WO2010148207A2 (en)	2009-06-18	2010-12-23	Arena Pharmaceuticals, Inc.	Processes 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
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1979
- 1979-06-05 ZA ZA792785A patent/ZA792785B/xx unknown
- 1979-06-11 IL IL57532A patent/IL57532A/xx unknown
- 1979-06-15 NZ NZ190745A patent/NZ190745A/xx unknown
- 1979-06-28 JP JP8252779A patent/JPS5511584A/ja active Granted
- 1979-07-02 CS CS794635A patent/CS213381B2/cs unknown
- 1979-07-02 PH PH22728A patent/PH15754A/en unknown
- 1979-07-02 DK DK278379A patent/DK156001C/da not_active IP Right Cessation
- 1979-07-02 PT PT69855A patent/PT69855A/pt unknown
- 1979-07-03 GR GR59498A patent/GR69675B/el unknown
- 1979-07-03 CA CA331,022A patent/CA1115271A/en not_active Expired
- 1979-07-03 AU AU48613/79A patent/AU525789B2/en not_active Ceased
- 1979-07-04 DE DE7979102279T patent/DE2964530D1/de not_active Expired
- 1979-07-04 EP EP82105188A patent/EP0080012B1/en not_active Expired
- 1979-07-04 EP EP79102279A patent/EP0007070B1/en not_active Expired
- 1979-07-05 FI FI792125A patent/FI67215C/fi not_active IP Right Cessation
- 1979-07-05 HU HU79SI1705A patent/HU179315B/hu unknown
- 1979-07-06 AR AR277218A patent/AR222828A1/es active
- 1979-07-06 SU SU792783746A patent/SU1029827A3/ru active
- 1979-07-06 IT IT24165/79A patent/IT1193190B/it active
- 1979-07-06 NO NO792267A patent/NO152213C/no unknown
- 1979-07-06 ES ES482276A patent/ES482276A1/es not_active Expired
- 1979-07-06 DD DD79214179A patent/DD147355A5/de unknown
- 1979-07-06 PL PL21690879A patent/PL216908A1/xx unknown
- 1979-07-06 ES ES482282A patent/ES482282A1/es not_active Expired
- 1979-07-06 ES ES482281A patent/ES482281A1/es not_active Expired
- 1979-07-07 JO JO19791273A patent/JO1273B1/en active
- 1979-08-08 IE IE1276/79A patent/IE48654B1/en unknown

Also Published As

Publication number	Publication date
JO1273B1 (en)	1986-11-30
IL57532A (en)	1982-08-31
ES482281A1 (es)	1980-04-01
HU179315B (en)	1982-09-28
DK156001C (da)	1989-11-06
NO152213B (no)	1985-05-13
PT69855A (en)	1979-08-01
FI67215B (fi)	1984-10-31
AR222828A1 (es)	1981-06-30
ES482276A1 (es)	1980-04-01
EP0080012A1 (en)	1983-06-01
AU4861379A (en)	1980-02-07
AU525789B2 (en)	1982-12-02
NZ190745A (en)	1981-01-23
NO152213C (no)	1985-08-28
GR69675B (da)	1982-07-07
IT1193190B (it)	1988-06-02
NO792267L (no)	1980-01-08
JPS5511584A (en)	1980-01-26
DK278379A (da)	1980-01-08
IT7924165A0 (it)	1979-07-06
ZA792785B (en)	1980-08-27
FI67215C (fi)	1985-02-11
EP0007070A1 (en)	1980-01-23
JPH0153271B2 (da)	1989-11-13
PL216908A1 (da)	1980-08-11
EP0007070B1 (en)	1983-01-19
IL57532A0 (en)	1979-10-31
PH15754A (en)	1983-03-18
IE48654B1 (en)	1985-04-03
SU1029827A3 (ru)	1983-07-15
EP0080012B1 (en)	1986-04-09
CA1115271A (en)	1981-12-29
IE791276L (en)	1980-01-07
FI792125A7 (fi)	1980-01-08
DE2964530D1 (en)	1983-02-24
CS213381B2 (en)	1982-04-09
ES482282A1 (es)	1980-04-01
DK156001B (da)	1989-06-12

Publication	Publication Date	Title
CA1115271A (en)	1981-12-29	Mercapto substituted-2,3,4,5-tetrahydro-1h-3- benzazepines
US4265890A (en)	1981-05-05	6-Phenyl thio- and 6-cyclohexyl thio-2,3,4,5-tetrahydro-1H-3-benzazepines
DD237510A5 (de)	1986-07-16	Verfahren zur herstellung von substituierten imidazo-(1,5-a)pyridin-derivaten
DE1695124A1 (de)	1970-08-20	Verfahren zur Herstellung von Tetrahydroazepinderivaten
DE60206762T2 (de)	2006-07-13	Hexahydroazepino(4,5-g)indole und -indoline als 5-ht rezeptor-liganden
DE1959405C3 (de)	1978-08-03	23-Dihydro-lH-dibenzo [23 zu 6,7] oxepine bzw. -thiepine [43-c] pyrrole, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zubereitungen
DE3402060A1 (de)	1985-08-01	Substituierte 5,11-dihydro-6h-dibenz(b,e)azepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE1445845A1 (de)	1969-02-06	Neue Benzomorphane und Verfahren zu ihrer Herstellung
DE1695929B2 (de)	1977-12-29	1,2-dihydro-1-hydroxy-2-imino-4-amino- 6-methylpyrimidine sowie ein verfahren zu deren herstellung
EP0059388B1 (de)	1985-05-29	Imidazodiazepine, Verfahren und Zwischenprodukte zu deren Herstellung, sowie diese enthaltende Arzneimittel
DE4444815A1 (de)	1996-06-20	Thienopyridone
DE3533675A1 (de)	1987-03-26	Neue 12- und 13-brom-ergolinderivate
DE2943286C2 (da)	1990-05-23
DE2456311A1 (de)	1975-06-05	Benzodiazepinderivate
CH641180A5 (de)	1984-02-15	Dibenzo(a.d)cycloocten-5,12(und 6,12)-imine.
DE1770030A1 (de)	1971-09-23	5-Hydroxy-5-phenyl-2,3-dihydro-5H-imidazo[2,1-a]-isoindole und Verfahren zu ihrer Herstellung
DE2600182A1 (de)	1976-07-08	Psychotrop und antimikrobiell wirksame polysubstituierte 10-piperazinodibenzo (b,f) thiepinderivate
DE2548737A1 (de)	1976-05-26	6-phenyl-spiro- eckige klammer auf cyclopropan-1,4'- eckige klammer auf 4h eckige klammer zu -s-triazolo eckige klammer auf 4,3-a eckige klammer zu - eckige klammer auf 1,4 eckige klammer zu benzodiazepine eckige klammer zu und verfahren zu deren herstellung
DE2209844C3 (de)	1980-05-14	4-(Alkylamino-alkyl)- [4H] -thieno [3,2-b] [f] benzazepine, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen
DE2520078A1 (de)	1975-11-20	Verfahren zur herstellung von neuen heterocyclischen s-imino-s-oxiden
KR830001501B1 (ko)	1983-08-03	메르캎토 치환-2, 3, 4, 5-테트라히드로-1h-3-벤자제핀류의 제조방법
DE2504595A1 (de)	1975-08-14	Dihydroanthracenderivate
IE48655B1 (en)	1985-04-03	6-chloro-3-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine,its acid addition salts and its use as an intermediate
DE2265051A1 (de)	1976-02-19	Neue substituierte xanthoncarbonsaeureamide
DE1942090A1 (de)	1970-02-26	Verfahren zur Herstellung neuer heterocyclischer Verbindungen