IE45900B1 - Decahydrocyclopent(c)azepines - Google Patents
Decahydrocyclopent(c)azepinesInfo
- Publication number
- IE45900B1 IE45900B1 IE2205/77A IE220577A IE45900B1 IE 45900 B1 IE45900 B1 IE 45900B1 IE 2205/77 A IE2205/77 A IE 2205/77A IE 220577 A IE220577 A IE 220577A IE 45900 B1 IE45900 B1 IE 45900B1
- Authority
- IE
- Ireland
- Prior art keywords
- decahydrocyclopent
- azepine
- hydrogen
- formula
- methoxyphenyl
- Prior art date
Links
- 150000001538 azepines Chemical class 0.000 title abstract description 24
- 150000001875 compounds Chemical class 0.000 claims description 68
- -1 C^-Cg cyeloalkyl Chemical group 0.000 claims description 59
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 59
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 238000005917 acylation reaction Methods 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 230000029936 alkylation Effects 0.000 claims description 9
- 238000005804 alkylation reaction Methods 0.000 claims description 9
- 230000010933 acylation Effects 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 238000006266 etherification reaction Methods 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 abstract description 7
- 239000000730 antalgic agent Substances 0.000 abstract description 7
- 229940035676 analgesics Drugs 0.000 abstract description 5
- 239000003887 narcotic antagonist Substances 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 46
- 239000011541 reaction mixture Substances 0.000 description 38
- 239000002904 solvent Substances 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 31
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000001704 evaporation Methods 0.000 description 24
- 230000008020 evaporation Effects 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 230000000202 analgesic effect Effects 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 12
- 239000012280 lithium aluminium hydride Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 10
- 229960005181 morphine Drugs 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- OUGDCMSKFYTDKN-UHFFFAOYSA-N 5a-(3-methoxyphenyl)-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepine Chemical compound COC1=CC=CC(C23C(CCC2)CNCCC3)=C1 OUGDCMSKFYTDKN-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- GPNUBZPACCOTQD-UHFFFAOYSA-N 2-diazoniocyclohexen-1-olate Chemical class [O-]C1=C([N+]#N)CCCC1 GPNUBZPACCOTQD-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002168 alkylating agent Substances 0.000 description 5
- 229940100198 alkylating agent Drugs 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- AJUMGSLQADLWKL-UHFFFAOYSA-N 1h-azepine;hydrochloride Chemical compound Cl.N1C=CC=CC=C1 AJUMGSLQADLWKL-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- WMSFPMZUOPITCA-UHFFFAOYSA-N 3-(3-formyl-2-oxo-1-phenylcyclohexyl)propanenitrile Chemical compound O=C1C(C=O)CCCC1(CCC#N)C1=CC=CC=C1 WMSFPMZUOPITCA-UHFFFAOYSA-N 0.000 description 3
- IODGSOGXNIWESM-UHFFFAOYSA-N 5a-phenyl-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepine Chemical compound C1CCC2CNCCCC21C1=CC=CC=C1 IODGSOGXNIWESM-UHFFFAOYSA-N 0.000 description 3
- IGKYEBKIMSGXEF-UHFFFAOYSA-N 6-(2-cyanoethyl)-2-diazonio-6-phenylcyclohexen-1-olate Chemical compound O=C1C(=[N+]=[N-])CCCC1(CCC#N)C1=CC=CC=C1 IGKYEBKIMSGXEF-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000012670 alkaline solution Substances 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000002243 cyclohexanonyl group Chemical class *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 description 3
- DPDCGVKTAWIGLD-UHFFFAOYSA-N cyclopenta[c]azepine Chemical compound C1=CN=CC2=CC=CC2=C1 DPDCGVKTAWIGLD-UHFFFAOYSA-N 0.000 description 3
- 150000001940 cyclopentanes Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KACQSVYTBQDRGP-UHFFFAOYSA-N 2-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC(C2C(CCCC2)=O)=C1 KACQSVYTBQDRGP-UHFFFAOYSA-N 0.000 description 2
- UKPLRVAKKXWITN-UHFFFAOYSA-N 2-cyclopentylethanamine Chemical class NCCC1CCCC1 UKPLRVAKKXWITN-UHFFFAOYSA-N 0.000 description 2
- BPPPUFSZQDCMEE-UHFFFAOYSA-N 2-oxocyclohexane-1-carbaldehyde Chemical class O=CC1CCCCC1=O BPPPUFSZQDCMEE-UHFFFAOYSA-N 0.000 description 2
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- CMRBKJLXLILWOH-UHFFFAOYSA-N 3-[3-formyl-1-(3-methoxyphenyl)-2-oxocyclohexyl]propanenitrile Chemical compound COC1=CC=CC(C2(CCC#N)C(C(C=O)CCC2)=O)=C1 CMRBKJLXLILWOH-UHFFFAOYSA-N 0.000 description 2
- BYDMZYVLOKZEJU-UHFFFAOYSA-N 6-(2-cyanoethyl)-2-diazonio-6-(3-methoxyphenyl)cyclohexen-1-olate Chemical compound COC1=CC=CC(C2(CCC#N)C(C(=[N+]=[N-])CCC2)=O)=C1 BYDMZYVLOKZEJU-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- NGPGDYLVALNKEG-UHFFFAOYSA-N azanium;azane;2,3,4-trihydroxy-4-oxobutanoate Chemical compound [NH4+].[NH4+].[O-]C(=O)C(O)C(O)C([O-])=O NGPGDYLVALNKEG-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000006345 epimerization reaction Methods 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000010453 quartz Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 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
- 239000008096 xylene Substances 0.000 description 2
- PFNPXGFYSGBCEM-UHFFFAOYSA-N (2,5a-diphenyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-1-yl)methanol Chemical compound OCC1C2CCCC2(C=2C=CC=CC=2)CCCN1C1=CC=CC=C1 PFNPXGFYSGBCEM-UHFFFAOYSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- ZJPCSAHEXFNXSN-IUCAKERBSA-N (5as,8ar)-1,2,3,4,5,5a,6,7,8,8a-decahydrocyclopenta[c]azepine Chemical class C1CCNC[C@@H]2CCC[C@H]21 ZJPCSAHEXFNXSN-IUCAKERBSA-N 0.000 description 1
- NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 description 1
- NQDIAMKPPGMQLS-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-4-iodobutan-1-one Chemical compound ClC1=CC=C(C(=O)CCCI)C=C1Cl NQDIAMKPPGMQLS-UHFFFAOYSA-N 0.000 description 1
- DOBLMFOFLYPUNN-UHFFFAOYSA-N 1-[5a-(3-methoxyphenyl)-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepin-1-yl]-2-(2-bromo-5-ethylphenyl)ethanone Chemical compound CCC1=CC=C(Br)C(CC(=O)C2C3CCCC3(CCCN2)C=2C=C(OC)C=CC=2)=C1 DOBLMFOFLYPUNN-UHFFFAOYSA-N 0.000 description 1
- MDCCBJLCTOTLKM-UHFFFAOYSA-N 1-bromo-3-methylpentane Chemical compound CCC(C)CCBr MDCCBJLCTOTLKM-UHFFFAOYSA-N 0.000 description 1
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 1
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical class C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 1
- RWFDBUMQNPBDLK-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)acetyl chloride Chemical compound CC1=CC=C(CC(Cl)=O)C=C1C RWFDBUMQNPBDLK-UHFFFAOYSA-N 0.000 description 1
- JQYJYABVJHYMDC-UHFFFAOYSA-N 2-(3-ethoxyphenyl)cyclohexan-1-one Chemical compound CCOC1=CC=CC(C2C(CCCC2)=O)=C1 JQYJYABVJHYMDC-UHFFFAOYSA-N 0.000 description 1
- WNQHCKFEVUMKOX-UHFFFAOYSA-N 2-(cyclopropylmethyl)-5a-(3-ethoxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound CCOC1=CC=CC(C23C(CCC2)CN(CC2CC2)CCC3)=C1 WNQHCKFEVUMKOX-UHFFFAOYSA-N 0.000 description 1
- VMDGYRMEGIXJJV-UHFFFAOYSA-N 2-(cyclopropylmethyl)-5a-(3-methoxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound COC1=CC=CC(C23C(CCC2)CN(CC2CC2)CCC3)=C1 VMDGYRMEGIXJJV-UHFFFAOYSA-N 0.000 description 1
- VUYGWDPJKQDJDY-UHFFFAOYSA-N 2-(furan-3-yl)acetyl bromide Chemical compound BrC(=O)CC=1C=COC=1 VUYGWDPJKQDJDY-UHFFFAOYSA-N 0.000 description 1
- IMQXJSBYIQDVIR-UHFFFAOYSA-N 2-(phenoxymethyl)-5a-phenyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound C1CCC2(C=3C=CC=CC=3)CCCC2CN1COC1=CC=CC=C1 IMQXJSBYIQDVIR-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- UCEXMJMSILZCHZ-UHFFFAOYSA-N 2-[(4-butoxybenzoyl)amino]acetic acid Chemical compound CCCCOC1=CC=C(C(=O)NCC(O)=O)C=C1 UCEXMJMSILZCHZ-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- ILXIYNJFHWINKQ-UHFFFAOYSA-N 2-benzyl-5a-phenyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine;hydroiodide Chemical compound I.C=1C=CC=CC=1CN(CC1CCC2)CCCC12C1=CC=CC=C1 ILXIYNJFHWINKQ-UHFFFAOYSA-N 0.000 description 1
- JJFOBACUIRKUPN-UHFFFAOYSA-N 2-bromoethoxybenzene Chemical compound BrCCOC1=CC=CC=C1 JJFOBACUIRKUPN-UHFFFAOYSA-N 0.000 description 1
- 125000006049 2-methyl-2-pentenyl group Chemical group 0.000 description 1
- HJWGSCXFRXXIGV-UHFFFAOYSA-N 2-phenylacetyl iodide Chemical compound IC(=O)CC1=CC=CC=C1 HJWGSCXFRXXIGV-UHFFFAOYSA-N 0.000 description 1
- DRLVMOAWNVOSPE-UHFFFAOYSA-N 2-phenylcyclohexan-1-one Chemical compound O=C1CCCCC1C1=CC=CC=C1 DRLVMOAWNVOSPE-UHFFFAOYSA-N 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
- LOIWEJTXXHOJFJ-UHFFFAOYSA-N 3,4,5,5a,6,7,8,8a-octahydro-2h-cyclopenta[c]azepin-1-one Chemical compound O=C1NCCCC2CCCC12 LOIWEJTXXHOJFJ-UHFFFAOYSA-N 0.000 description 1
- XQSXPZFSYNNDJT-UHFFFAOYSA-N 3-(2-fluorophenyl)propanoyl bromide Chemical compound FC1=CC=CC=C1CCC(Br)=O XQSXPZFSYNNDJT-UHFFFAOYSA-N 0.000 description 1
- MGOAALJPOWOSOG-UHFFFAOYSA-N 3-(2-methyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-5a-yl)phenol;hydrochloride Chemical compound Cl.C1CCC2CN(C)CCCC21C1=CC=CC(O)=C1 MGOAALJPOWOSOG-UHFFFAOYSA-N 0.000 description 1
- ULQSBYHOJARFRN-UHFFFAOYSA-N 3-(2-oxo-1-phenylcyclohexyl)propanenitrile Chemical compound O=C1CCCCC1(CCC#N)C1=CC=CC=C1 ULQSBYHOJARFRN-UHFFFAOYSA-N 0.000 description 1
- SPTVCXKSSRBTMN-UHFFFAOYSA-N 3-(2-oxocyclohexyl)propanenitrile Chemical compound O=C1CCCCC1CCC#N SPTVCXKSSRBTMN-UHFFFAOYSA-N 0.000 description 1
- WLVCBAMXYMWGLJ-UHFFFAOYSA-N 3-(chloromethyl)heptane Chemical compound CCCCC(CC)CCl WLVCBAMXYMWGLJ-UHFFFAOYSA-N 0.000 description 1
- PJIGXWFIYCCHEC-UHFFFAOYSA-N 3-[1-(3-ethoxyphenyl)-3-formyl-2-oxocyclohexyl]propanenitrile Chemical compound CCOC1=CC=CC(C2(CCC#N)C(C(C=O)CCC2)=O)=C1 PJIGXWFIYCCHEC-UHFFFAOYSA-N 0.000 description 1
- MVHQTKSQGZETRY-UHFFFAOYSA-N 3-[1-(3-methoxyphenyl)-2-oxocyclohexyl]propanenitrile Chemical compound COC1=CC=CC(C2(CCC#N)C(CCCC2)=O)=C1 MVHQTKSQGZETRY-UHFFFAOYSA-N 0.000 description 1
- JKGLBDLNPDSEOW-UHFFFAOYSA-N 3-[2-(3-methylbutyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-5a-yl]phenol Chemical compound C1CCC2CN(CCC(C)C)CCCC21C1=CC=CC(O)=C1 JKGLBDLNPDSEOW-UHFFFAOYSA-N 0.000 description 1
- DAULYEKOPWYLPO-UHFFFAOYSA-N 3-[2-(cyclobutylmethyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-5a-yl]phenol;phosphoric acid Chemical compound OP(O)(O)=O.OC1=CC=CC(C23C(CCC2)CN(CC2CCC2)CCC3)=C1 DAULYEKOPWYLPO-UHFFFAOYSA-N 0.000 description 1
- VFBRYGXYLHSDEV-UHFFFAOYSA-N 3-[2-(phenylsulfanylmethyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-5a-yl]phenol Chemical compound OC1=CC=CC(C23C(CCC2)CN(CSC=2C=CC=CC=2)CCC3)=C1 VFBRYGXYLHSDEV-UHFFFAOYSA-N 0.000 description 1
- ASIKSPSJJIDUGO-UHFFFAOYSA-N 3-iodopropylsulfanylbenzene Chemical compound ICCCSC1=CC=CC=C1 ASIKSPSJJIDUGO-UHFFFAOYSA-N 0.000 description 1
- SDTVFLXEAYMCQE-UHFFFAOYSA-N 3-phenylpropanethioyl bromide Chemical compound BrC(=S)CCC1=CC=CC=C1 SDTVFLXEAYMCQE-UHFFFAOYSA-N 0.000 description 1
- OCFAQPCFDHNVMO-UHFFFAOYSA-N 4-(3-methylphenoxy)butanoyl bromide Chemical compound CC1=CC=CC(OCCCC(Br)=O)=C1 OCFAQPCFDHNVMO-UHFFFAOYSA-N 0.000 description 1
- WKEVRZCQFQDCIR-UHFFFAOYSA-N 4-chlorobut-1-ene Chemical compound ClCCC=C WKEVRZCQFQDCIR-UHFFFAOYSA-N 0.000 description 1
- UBJQMLSBJBOAJV-UHFFFAOYSA-N 5-bromo-3,4-dimethylpent-2-ene Chemical compound CC=C(C)C(C)CBr UBJQMLSBJBOAJV-UHFFFAOYSA-N 0.000 description 1
- ORDNGGBEXPVNLM-UHFFFAOYSA-N 5a-(3-ethoxyphenyl)-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepine Chemical compound CCOC1=CC=CC(C23C(CCC2)CNCCC3)=C1 ORDNGGBEXPVNLM-UHFFFAOYSA-N 0.000 description 1
- MMTLWPCYZVOQJJ-UHFFFAOYSA-N 5a-(3-ethoxyphenyl)-2-ethyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine;hydroiodide Chemical compound I.CCOC1=CC=CC(C23C(CCC2)CN(CC)CCC3)=C1 MMTLWPCYZVOQJJ-UHFFFAOYSA-N 0.000 description 1
- OGPZQKANESCCLE-UHFFFAOYSA-N 5a-(3-methoxyphenyl)-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepine;hydrobromide Chemical compound Br.COC1=CC=CC(C23C(CCC2)CNCCC3)=C1 OGPZQKANESCCLE-UHFFFAOYSA-N 0.000 description 1
- YQGQTPNVEIPAJR-UHFFFAOYSA-N 5a-(3-methoxyphenyl)-2-(2-phenylethyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound COC1=CC=CC(C23C(CCC2)CN(CCC=2C=CC=CC=2)CCC3)=C1 YQGQTPNVEIPAJR-UHFFFAOYSA-N 0.000 description 1
- USAKNCXOTXOEMG-UHFFFAOYSA-N 5a-(3-methoxyphenyl)-2-methyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound COC1=CC=CC(C23C(CCC2)CN(C)CCC3)=C1 USAKNCXOTXOEMG-UHFFFAOYSA-N 0.000 description 1
- QXJUWXCIYDZBQD-UHFFFAOYSA-N 5a-(3-methoxyphenyl)-2-prop-2-enyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine;hydrochloride Chemical compound Cl.COC1=CC=CC(C23C(CCC2)CN(CC=C)CCC3)=C1 QXJUWXCIYDZBQD-UHFFFAOYSA-N 0.000 description 1
- DCJAXZYNQUJNGY-UHFFFAOYSA-N 5a-(3-propoxyphenyl)-2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepine Chemical compound CCCOC1=CC=CC(C23C(CCC2)CNCCC3)=C1 DCJAXZYNQUJNGY-UHFFFAOYSA-N 0.000 description 1
- GQYOMFTYKLLXGG-UHFFFAOYSA-N 6-(2-cyanoethyl)-2-diazonio-6-(3-propoxyphenyl)cyclohexen-1-olate Chemical compound CCCOC1=CC=CC(C2(CCC#N)C(C(=[N+]=[N-])CCC2)=O)=C1 GQYOMFTYKLLXGG-UHFFFAOYSA-N 0.000 description 1
- QTCKFQMYOMTINU-UHFFFAOYSA-N 6-iodohex-1-ene Chemical compound ICCCCC=C QTCKFQMYOMTINU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OXBXAVZFUVZBJY-UHFFFAOYSA-N C(=O)=CC1=CCCCC1 Chemical compound C(=O)=CC1=CCCCC1 OXBXAVZFUVZBJY-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 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
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- AUMTWVZSLXBRBF-UHFFFAOYSA-N [3-(2,3,4,5,6,7,8,8a-octahydro-1h-cyclopenta[c]azepin-5a-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C23C(CCC2)CNCCC3)=C1 AUMTWVZSLXBRBF-UHFFFAOYSA-N 0.000 description 1
- IHUQCAKQHKQIBX-UHFFFAOYSA-N [3-(2-oct-7-enyl-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-5a-yl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC(C23C(CCC2)CN(CCCCCCC=C)CCC3)=C1 IHUQCAKQHKQIBX-UHFFFAOYSA-N 0.000 description 1
- CZGPQFYEOFGNGN-UHFFFAOYSA-N [5a-(3-hydroxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-2-yl]-cyclobutylmethanone Chemical compound OC1=CC=CC(C23C(CCC2)CN(CCC3)C(=O)C2CCC2)=C1 CZGPQFYEOFGNGN-UHFFFAOYSA-N 0.000 description 1
- LWNROFQVBUHQKP-UHFFFAOYSA-N [5a-(3-methoxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-2-yl]-(furan-3-yl)methanone Chemical compound COC1=CC=CC(C23C(CCC2)CN(CCC3)C(=O)C2=COC=C2)=C1 LWNROFQVBUHQKP-UHFFFAOYSA-N 0.000 description 1
- JPIRPDCUXSVRIA-UHFFFAOYSA-N [5a-(3-methoxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepin-2-yl]-cyclopropylmethanone Chemical compound COC1=CC=CC(C23C(CCC2)CN(CCC3)C(=O)C2CC2)=C1 JPIRPDCUXSVRIA-UHFFFAOYSA-N 0.000 description 1
- JRVORWMACMEOAD-UHFFFAOYSA-N [N].C1=NC=CC2=CC=CC=C21 Chemical group [N].C1=NC=CC2=CC=CC=C21 JRVORWMACMEOAD-UHFFFAOYSA-N 0.000 description 1
- SBCZFLCCMWEZJA-UHFFFAOYSA-N acetic acid;2-(3-methylhexyl)-5a-(3-propoxyphenyl)-1,3,4,5,6,7,8,8a-octahydrocyclopenta[c]azepine Chemical compound CC(O)=O.CCCOC1=CC=CC(C23C(CCC2)CN(CCC(C)CCC)CCC3)=C1 SBCZFLCCMWEZJA-UHFFFAOYSA-N 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- LDLKUPVDJGDYCK-UHFFFAOYSA-N cyclohexanecarbonyl bromide Chemical compound BrC(=O)C1CCCCC1 LDLKUPVDJGDYCK-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- GNNILMDCYQGMRH-UHFFFAOYSA-N formyl benzoate Chemical compound O=COC(=O)C1=CC=CC=C1 GNNILMDCYQGMRH-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- BSUODTDYSTUDAV-UHFFFAOYSA-N hex-3-enoyl chloride Chemical compound CCC=CCC(Cl)=O BSUODTDYSTUDAV-UHFFFAOYSA-N 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- QVUVUYORCPGRQX-UHFFFAOYSA-N methyl 2-(2-cyanoethyl)-2-(3-methoxyphenyl)cyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1(CCC#N)C1=CC=CC(OC)=C1 QVUVUYORCPGRQX-UHFFFAOYSA-N 0.000 description 1
- WLDIYJUQIWTCSI-UHFFFAOYSA-N methyl 2-(2-cyanoethyl)-2-phenylcyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1(CCC#N)C1=CC=CC=C1 WLDIYJUQIWTCSI-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- ZTHRQJQJODGZHV-UHFFFAOYSA-N n-phenylpropanamide Chemical class CCC(=O)NC1=CC=CC=C1 ZTHRQJQJODGZHV-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000000945 opiatelike Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940065347 propoxyphene hydrochloride Drugs 0.000 description 1
- GWMZVNJINHYFDV-UHFFFAOYSA-N propyl 2-(2-cyanoethyl)-2-(3-propoxyphenyl)cyclopentane-1-carboxylate Chemical compound CCCOC(=O)C1CCCC1(CCC#N)C1=CC=CC(OCCC)=C1 GWMZVNJINHYFDV-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007157 ring contraction reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil 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
- C07D223/32—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems containing carbocyclic rings other than six-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/737,957 US4141893A (en) | 1976-11-02 | 1976-11-02 | Decahydrocyclopent[c]azepines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE45900L IE45900L (en) | 1978-05-02 |
| IE45900B1 true IE45900B1 (en) | 1982-12-29 |
Family
ID=24965975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2205/77A IE45900B1 (en) | 1976-11-02 | 1977-10-28 | Decahydrocyclopent(c)azepines |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4141893A (esLanguage) |
| JP (1) | JPS5356682A (esLanguage) |
| AT (1) | AT359067B (esLanguage) |
| AU (1) | AU514786B2 (esLanguage) |
| BE (1) | BE860313A (esLanguage) |
| BG (1) | BG28418A3 (esLanguage) |
| CA (1) | CA1094554A (esLanguage) |
| DD (1) | DD133796A5 (esLanguage) |
| DE (1) | DE2748467A1 (esLanguage) |
| DK (1) | DK485377A (esLanguage) |
| ES (2) | ES463785A1 (esLanguage) |
| FR (1) | FR2369269A1 (esLanguage) |
| GB (1) | GB1585297A (esLanguage) |
| GR (1) | GR70054B (esLanguage) |
| IE (1) | IE45900B1 (esLanguage) |
| IL (1) | IL53237A0 (esLanguage) |
| NL (1) | NL7712051A (esLanguage) |
| NZ (1) | NZ185538A (esLanguage) |
| PL (2) | PL108031B1 (esLanguage) |
| PT (1) | PT67193B (esLanguage) |
| RO (1) | RO73087B (esLanguage) |
| SE (1) | SE7712217L (esLanguage) |
| SU (1) | SU727141A3 (esLanguage) |
| YU (1) | YU257477A (esLanguage) |
| ZA (1) | ZA776499B (esLanguage) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3704661A1 (de) * | 1987-02-14 | 1988-08-25 | Hoechst Ag | Annelierte azepinon- und azocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT330179B (de) * | 1972-07-20 | 1976-06-25 | Du Pont | Verfahren zur herstellung von neuen 4a-aryl- transdecahydroisochinolinderivaten sowie deren optischen isomeren |
| US4001247A (en) * | 1974-06-07 | 1977-01-04 | Eli Lilly And Company | 1-ethyl 3a-(substituted-phenyl) decahydroisoquinoline |
| US4001248A (en) * | 1974-06-07 | 1977-01-04 | Eli Lilly And Company | N-cycloalkylmethyl decahydroisoquinolines |
-
1976
- 1976-11-02 US US05/737,957 patent/US4141893A/en not_active Expired - Lifetime
-
1977
- 1977-10-26 PT PT67193A patent/PT67193B/pt unknown
- 1977-10-27 CA CA289,696A patent/CA1094554A/en not_active Expired
- 1977-10-27 NZ NZ185538A patent/NZ185538A/xx unknown
- 1977-10-27 YU YU02574/77A patent/YU257477A/xx unknown
- 1977-10-27 GB GB44730/77A patent/GB1585297A/en not_active Expired
- 1977-10-27 IL IL53237A patent/IL53237A0/xx unknown
- 1977-10-28 BE BE1008482A patent/BE860313A/xx unknown
- 1977-10-28 SE SE7712217A patent/SE7712217L/xx unknown
- 1977-10-28 FR FR7732775A patent/FR2369269A1/fr active Granted
- 1977-10-28 DE DE19772748467 patent/DE2748467A1/de not_active Withdrawn
- 1977-10-28 IE IE2205/77A patent/IE45900B1/en unknown
- 1977-11-01 AU AU30234/77A patent/AU514786B2/en not_active Expired
- 1977-11-01 ZA ZA00776499A patent/ZA776499B/xx unknown
- 1977-11-01 DK DK485377A patent/DK485377A/da unknown
- 1977-11-01 NL NL7712051A patent/NL7712051A/xx not_active Application Discontinuation
- 1977-11-01 BG BG037701A patent/BG28418A3/xx unknown
- 1977-11-02 SU SU772538948A patent/SU727141A3/ru active
- 1977-11-02 JP JP13211077A patent/JPS5356682A/ja active Pending
- 1977-11-02 PL PL1977201884A patent/PL108031B1/pl unknown
- 1977-11-02 PL PL1977215629A patent/PL112151B1/pl unknown
- 1977-11-02 DD DD7700201830A patent/DD133796A5/xx unknown
- 1977-11-02 RO RO7792003A patent/RO73087B/ro unknown
- 1977-11-02 ES ES463785A patent/ES463785A1/es not_active Expired
- 1977-11-02 AT AT782077A patent/AT359067B/de not_active IP Right Cessation
- 1977-12-29 GR GR54665A patent/GR70054B/el unknown
-
1978
- 1978-07-27 ES ES472121A patent/ES472121A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ATA782077A (de) | 1980-03-15 |
| ES472121A1 (es) | 1979-04-01 |
| ES463785A1 (es) | 1979-10-16 |
| PL112151B1 (en) | 1980-09-30 |
| AU3023477A (en) | 1979-05-10 |
| SE7712217L (sv) | 1978-05-03 |
| IL53237A0 (en) | 1977-12-30 |
| AU514786B2 (en) | 1981-02-26 |
| BG28418A3 (en) | 1980-04-15 |
| NL7712051A (nl) | 1978-05-05 |
| US4141893A (en) | 1979-02-27 |
| RO73087B (ro) | 1981-08-20 |
| CA1094554A (en) | 1981-01-27 |
| FR2369269B1 (esLanguage) | 1980-05-16 |
| PL108031B1 (pl) | 1980-03-31 |
| GB1585297A (en) | 1981-02-25 |
| FR2369269A1 (fr) | 1978-05-26 |
| DE2748467A1 (de) | 1978-05-03 |
| DD133796A5 (de) | 1979-01-24 |
| IE45900L (en) | 1978-05-02 |
| DK485377A (da) | 1978-05-03 |
| NZ185538A (en) | 1979-06-08 |
| PT67193A (en) | 1977-11-01 |
| JPS5356682A (en) | 1978-05-23 |
| PT67193B (en) | 1979-03-22 |
| GR70054B (esLanguage) | 1982-07-26 |
| SU727141A3 (ru) | 1980-04-05 |
| ZA776499B (en) | 1979-06-27 |
| PL201884A1 (pl) | 1978-12-04 |
| AT359067B (de) | 1980-10-27 |
| BE860313A (fr) | 1978-04-28 |
| YU257477A (en) | 1983-01-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4152450A (en) | 9-Amino-dibenzopyrans | |
| US4337341A (en) | 4a-Aryl-octahydro-1H-2-pyrindines | |
| AU2006286824A1 (en) | Organic compounds | |
| US4277605A (en) | Chemical compounds | |
| US3700734A (en) | 2{40 -hydroxy-2,3,5-trimethyl-6,7-benzomorphan | |
| US4100166A (en) | Novel cis N-cyclopropylmethyl decahydroisoquinoline | |
| US3138603A (en) | New benzomorphans (methanobenzazocines) and preparation thereof | |
| US7476679B2 (en) | Octahydroisoquinoline compounds as opioid receptor modulators | |
| US3513169A (en) | 5,9-diethyl benzomorphan derivatives | |
| CA2064465A1 (en) | Orally active nonaddicting analgesics | |
| CA1105026A (en) | 4a-aryl-octahydro-1h-2-pyrindines | |
| CA1100136A (en) | 4a-aryl octahydro-1h-2-pyrindines | |
| US4141893A (en) | Decahydrocyclopent[c]azepines | |
| CA1148150A (en) | Phenylmorphans, intermediates and method of preparation | |
| US3914232A (en) | 2-And 4-acryloxy-N-substituted-morphinan derivatives | |
| US5258384A (en) | S-11-hydroxy-10-methylaporphine and its biologically active salt forms as 5HT1A inhibitors | |
| US4141894A (en) | Trans-5a-aryl-decahydrobenzazepines | |
| US4278797A (en) | Intermediates to phenylmorphans and method of preparation thereof | |
| EP0051190A2 (en) | N-(amino(or hydroxy) phenethyl)-1,2,3,4-tetrahydroisoquinolines, precursors thereof, and methods of preparation | |
| CA2223646A1 (en) | Novel heterocyclic compounds for the treatment of pain and use thereof | |
| US4195025A (en) | 9-Amino-dibenzopyrans | |
| US4281130A (en) | Lower-alkyl 4,6,7,8,8a-9-hexahydro-6,9-ethanothieno[3,2-f]indolizine-10-carboxylate | |
| US4996223A (en) | New organic compounds having opioid properties | |
| CA1119175A (en) | 4a-aryl octahydro-1h-2-pyrindines | |
| JPS6212221B2 (esLanguage) |