CA1080705A - Azabicycloalkanes and precursors thereof - Google Patents
Azabicycloalkanes and precursors thereofInfo
- Publication number
- CA1080705A CA1080705A CA248,298A CA248298A CA1080705A CA 1080705 A CA1080705 A CA 1080705A CA 248298 A CA248298 A CA 248298A CA 1080705 A CA1080705 A CA 1080705A
- Authority
- CA
- Canada
- Prior art keywords
- octane
- azabicyclo
- methoxyphenyl
- resultant
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000002243 precursor Substances 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 103
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 101
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 74
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 230000008569 process Effects 0.000 claims description 49
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 42
- 239000000047 product Substances 0.000 claims description 42
- 229910052794 bromium Inorganic materials 0.000 claims description 39
- QPAOLGRRDDZZGP-UHFFFAOYSA-N 5-(3-methoxyphenyl)-2-methyl-2-azabicyclo[3.2.1]octan-8-one Chemical compound COC1=CC=CC(C23CCN(C)C(CC2)C3=O)=C1 QPAOLGRRDDZZGP-UHFFFAOYSA-N 0.000 claims description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
- -1 methoxy, hydroxy Chemical group 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 26
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 23
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 claims description 22
- MBFNRLNZIHAMFE-UHFFFAOYSA-N 5-(3-methoxyphenyl)-2-azabicyclo[3.2.1]octane Chemical compound COC1=CC=CC(C23CC(CC2)NCC3)=C1 MBFNRLNZIHAMFE-UHFFFAOYSA-N 0.000 claims description 21
- AUMHLYHVBLXFAN-UHFFFAOYSA-N 5-(3-methoxyphenyl)-2-methyl-2-azabicyclo[3.2.1]octane Chemical compound COC1=CC=CC(C23CC(CC2)N(C)CC3)=C1 AUMHLYHVBLXFAN-UHFFFAOYSA-N 0.000 claims description 21
- 229910021529 ammonia Inorganic materials 0.000 claims description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 20
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 20
- 238000010438 heat treatment Methods 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 19
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 17
- DUKMAFVNEKXIMP-UHFFFAOYSA-N 5-bromo-2-[2-(dimethylamino)ethyl]-2-(3-methoxyphenyl)cyclopentan-1-one;hydrobromide Chemical compound Br.COC1=CC=CC(C2(CCN(C)C)C(C(Br)CC2)=O)=C1 DUKMAFVNEKXIMP-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 150000002989 phenols Chemical class 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 150000003512 tertiary amines Chemical class 0.000 claims description 5
- FOHPXJOQTHBXQQ-UHFFFAOYSA-N 3-(2-propyl-2-azabicyclo[3.2.1]octan-5-yl)phenol Chemical compound C1CC(C2)N(CCC)CCC21C1=CC=CC(O)=C1 FOHPXJOQTHBXQQ-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- GUSVHTGHWCRLNP-UHFFFAOYSA-N 2-(furan-2-yl)acetyl chloride Chemical compound ClC(=O)CC1=CC=CO1 GUSVHTGHWCRLNP-UHFFFAOYSA-N 0.000 claims description 3
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 claims description 3
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 claims description 3
- IREBRYIHHBBBKN-UHFFFAOYSA-N 3-(2-azabicyclo[3.2.1]octan-5-yl)phenol Chemical compound OC1=CC=CC(C23CC(CC2)NCC3)=C1 IREBRYIHHBBBKN-UHFFFAOYSA-N 0.000 claims description 3
- FYCHIQRUNQXKBM-UHFFFAOYSA-N 3-(2-butyl-2-azabicyclo[3.2.1]octan-5-yl)phenol Chemical compound C1CC(C2)N(CCCC)CCC21C1=CC=CC(O)=C1 FYCHIQRUNQXKBM-UHFFFAOYSA-N 0.000 claims description 3
- RJXIFCNJWFWHGK-UHFFFAOYSA-N 3-[2-(cyclopropylmethyl)-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CC2CC2)CC3)=C1 RJXIFCNJWFWHGK-UHFFFAOYSA-N 0.000 claims description 3
- QZQGZNJGUMCHSX-UHFFFAOYSA-N 5-(3-methoxyphenyl)-1-(2-phenylethyl)-2-azabicyclo[3.2.1]octane Chemical compound COC1=CC=CC(C23CC(CCC=4C=CC=CC=4)(CC2)NCC3)=C1 QZQGZNJGUMCHSX-UHFFFAOYSA-N 0.000 claims description 3
- HXTWVFGWJFGIDM-UHFFFAOYSA-N 5-(4-methoxyphenyl)-2-methyl-2-azabicyclo[3.2.1]octan-8-one Chemical compound C1=CC(OC)=CC=C1C1(C2=O)CCN(C)C2CC1 HXTWVFGWJFGIDM-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- IOCSRYQDPSCMCH-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[5-(3-hydroxyphenyl)-2-azabicyclo[3.2.1]octan-2-yl]butan-1-one Chemical compound OC1=CC=CC(C23CC(CC2)N(CCCC(=O)C=2C=CC(F)=CC=2)CC3)=C1 IOCSRYQDPSCMCH-UHFFFAOYSA-N 0.000 claims description 2
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 claims description 2
- CJJURHKDGQSBLE-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C(Cl)=C1 CJJURHKDGQSBLE-UHFFFAOYSA-N 0.000 claims description 2
- PYPMKORNJLTHGP-UHFFFAOYSA-N 2-(3-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=CC(Cl)=C1 PYPMKORNJLTHGP-UHFFFAOYSA-N 0.000 claims description 2
- UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 claims description 2
- AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 claims description 2
- XTMCOTVROPYRKA-UHFFFAOYSA-N 5-bromo-2-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)cyclopentan-1-one;hydrobromide Chemical compound Br.C1=CC(OC)=CC=C1C1(CCN(C)C)C(=O)C(Br)CC1 XTMCOTVROPYRKA-UHFFFAOYSA-N 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 36
- 229960001407 sodium bicarbonate Drugs 0.000 claims 6
- IRGGMTQKLTZNPN-UHFFFAOYSA-N 3-(2-ethyl-2-azabicyclo[3.2.1]octan-5-yl)phenol Chemical compound C1CC(C2)N(CC)CCC21C1=CC=CC(O)=C1 IRGGMTQKLTZNPN-UHFFFAOYSA-N 0.000 claims 2
- LRUVFOACLHPGOI-UHFFFAOYSA-N 3-[2-[2-(3,4-dichlorophenyl)ethyl]-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CCC=2C=C(Cl)C(Cl)=CC=2)CC3)=C1 LRUVFOACLHPGOI-UHFFFAOYSA-N 0.000 claims 2
- VVAJVVRIMGVAIB-UHFFFAOYSA-N 3-[2-[2-(furan-2-yl)ethyl]-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CCC=2OC=CC=2)CC3)=C1 VVAJVVRIMGVAIB-UHFFFAOYSA-N 0.000 claims 2
- GTUIXPUWWADVRZ-UHFFFAOYSA-N 4-(2-methyl-2-azabicyclo[3.2.1]octan-5-yl)phenol Chemical compound C1CC(C2)N(C)CCC21C1=CC=C(O)C=C1 GTUIXPUWWADVRZ-UHFFFAOYSA-N 0.000 claims 2
- YEMSLDJMKASAOH-UHFFFAOYSA-N [3-(2-methyl-2-azabicyclo[3.2.1]octan-5-yl)phenyl] acetate Chemical compound C1CC(C2)N(C)CCC21C1=CC=CC(OC(C)=O)=C1 YEMSLDJMKASAOH-UHFFFAOYSA-N 0.000 claims 2
- KFUNFKVDSTVFRW-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[5-(3-methoxyphenyl)-2-azabicyclo[3.2.1]octan-2-yl]butan-1-one Chemical compound COC1=CC=CC(C23CC(CC2)N(CCCC(=O)C=2C=CC(F)=CC=2)CC3)=C1 KFUNFKVDSTVFRW-UHFFFAOYSA-N 0.000 claims 1
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 claims 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- VIIRVTIKFUISQQ-UHFFFAOYSA-N 3-[1-(2-phenylethyl)-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CCC=4C=CC=CC=4)(CC2)NCC3)=C1 VIIRVTIKFUISQQ-UHFFFAOYSA-N 0.000 claims 1
- LFFNEDXLQHJJRP-UHFFFAOYSA-N 3-[2-(2-thiophen-2-ylethyl)-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CCC=2SC=CC=2)CC3)=C1 LFFNEDXLQHJJRP-UHFFFAOYSA-N 0.000 claims 1
- UNFKTIOWYJUFAN-UHFFFAOYSA-N 3-[2-(furan-2-ylmethyl)-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CC=2OC=CC=2)CC3)=C1 UNFKTIOWYJUFAN-UHFFFAOYSA-N 0.000 claims 1
- PRBGTKGBELJOPA-UHFFFAOYSA-N 3-[2-[2-(3-chlorophenyl)ethyl]-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CCC=2C=C(Cl)C=CC=2)CC3)=C1 PRBGTKGBELJOPA-UHFFFAOYSA-N 0.000 claims 1
- BWCNXXZVHGRQJW-UHFFFAOYSA-N 3-[2-[2-(4-chlorophenyl)ethyl]-2-azabicyclo[3.2.1]octan-5-yl]phenol Chemical compound OC1=CC=CC(C23CC(CC2)N(CCC=2C=CC(Cl)=CC=2)CC3)=C1 BWCNXXZVHGRQJW-UHFFFAOYSA-N 0.000 claims 1
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 229910052799 carbon Inorganic materials 0.000 description 57
- 229910052757 nitrogen Inorganic materials 0.000 description 53
- 238000004458 analytical method Methods 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 229960001701 chloroform Drugs 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 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 12
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 230000000202 analgesic effect Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960005181 morphine Drugs 0.000 description 6
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 150000003335 secondary amines Chemical class 0.000 description 6
- 229960000443 hydrochloric acid Drugs 0.000 description 5
- 235000011167 hydrochloric acid Nutrition 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- PPWHSTMDJUJTPE-UHFFFAOYSA-N 2-(4-methoxyphenyl)cyclopentan-1-one Chemical compound C1=CC(OC)=CC=C1C1C(=O)CCC1 PPWHSTMDJUJTPE-UHFFFAOYSA-N 0.000 description 4
- CODNABFMAXSUTH-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)cyclopentan-1-one Chemical compound C1=CC(OC)=CC=C1C1(CCN(C)C)C(=O)CCC1 CODNABFMAXSUTH-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- STHHLVCQSLRQNI-UHFFFAOYSA-N 1-azabicyclo[3.2.1]octane Chemical compound C1C2CCN1CCC2 STHHLVCQSLRQNI-UHFFFAOYSA-N 0.000 description 3
- NWYHKEDTJXNXSX-UHFFFAOYSA-N 2-[3-(dimethylamino)propyl]-2-(3-methoxyphenyl)cyclopentan-1-one Chemical compound COC1=CC=CC(C2(CCCN(C)C)C(CCC2)=O)=C1 NWYHKEDTJXNXSX-UHFFFAOYSA-N 0.000 description 3
- FPEVMEILLQOJHD-UHFFFAOYSA-N 3-(2-azabicyclo[3.2.1]octan-5-yl)phenol;hydrobromide Chemical compound Br.OC1=CC=CC(C23CC(CC2)NCC3)=C1 FPEVMEILLQOJHD-UHFFFAOYSA-N 0.000 description 3
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- AQQRQDZGYJHKHD-UHFFFAOYSA-N n-[4-[2-[5-(3-hydroxyphenyl)-2-azabicyclo[3.2.1]octan-2-yl]ethyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CCN1C(C2)CCC2(C=2C=C(O)C=CC=2)CC1 AQQRQDZGYJHKHD-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008096 xylene 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56051075A | 1975-03-20 | 1975-03-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1080705A true CA1080705A (en) | 1980-07-01 |
Family
ID=24238098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA248,298A Expired CA1080705A (en) | 1975-03-20 | 1976-03-19 | Azabicycloalkanes and precursors thereof |
Country Status (22)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4278797A (en) * | 1979-03-12 | 1981-07-14 | Eli Lilly And Company | Intermediates to phenylmorphans and method of preparation thereof |
| AU566673B2 (en) * | 1983-09-15 | 1987-10-29 | F. Hoffmann-La Roche Ag | Phenethylamine derivatives |
| DE3707911C1 (de) * | 1987-03-12 | 1988-03-31 | Texaco Ag | Bicyclische Aminkatalysatoren |
-
1976
- 1976-02-13 IL IL49034A patent/IL49034A/xx unknown
- 1976-03-13 ES ES446051A patent/ES446051A1/es not_active Expired
- 1976-03-13 DE DE19762610702 patent/DE2610702A1/de not_active Withdrawn
- 1976-03-15 NL NL7602681A patent/NL7602681A/xx not_active Application Discontinuation
- 1976-03-17 SE SE7603355A patent/SE7603355L/xx unknown
- 1976-03-18 FR FR7607839A patent/FR2304331A1/fr active Granted
- 1976-03-18 GR GR50346A patent/GR59319B/el unknown
- 1976-03-18 AU AU12157/76A patent/AU1215776A/en not_active Expired
- 1976-03-18 LU LU74590A patent/LU74590A1/xx unknown
- 1976-03-18 FI FI760727A patent/FI760727A7/fi not_active Application Discontinuation
- 1976-03-18 GB GB10931/76A patent/GB1538152A/en not_active Expired
- 1976-03-19 MX MX76102U patent/MX3511E/es unknown
- 1976-03-19 DK DK120676A patent/DK120676A/da unknown
- 1976-03-19 IE IE585/76A patent/IE42787B1/en unknown
- 1976-03-19 ZA ZA761715A patent/ZA761715B/xx unknown
- 1976-03-19 AT AT207076A patent/AT360010B/de not_active IP Right Cessation
- 1976-03-19 CA CA248,298A patent/CA1080705A/en not_active Expired
- 1976-03-19 JP JP51030720A patent/JPS51122046A/ja active Pending
- 1976-03-19 PT PT64922A patent/PT64922B/pt unknown
- 1976-03-19 NO NO760976A patent/NO760976L/no unknown
- 1976-03-22 BE BE165443A patent/BE839886A/xx unknown
- 1976-10-14 US US05/732,415 patent/US4079141A/en not_active Expired - Lifetime
- 1976-11-10 FR FR7633965A patent/FR2346002A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| GB1538152A (en) | 1979-01-10 |
| ATA207076A (de) | 1980-05-15 |
| FI760727A7 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1976-09-21 |
| AT360010B (de) | 1980-12-10 |
| ES446051A1 (es) | 1977-09-16 |
| NL7602681A (nl) | 1976-09-22 |
| GR59319B (en) | 1977-12-12 |
| MX3511E (es) | 1981-01-14 |
| IL49034A0 (en) | 1976-04-30 |
| IE42787L (en) | 1976-09-20 |
| SE7603355L (sv) | 1976-09-21 |
| PT64922B (de) | 1977-11-17 |
| AU1215776A (en) | 1977-09-22 |
| BE839886A (fr) | 1976-09-22 |
| JPS51122046A (en) | 1976-10-25 |
| ZA761715B (en) | 1977-04-27 |
| DK120676A (da) | 1976-09-21 |
| IE42787B1 (en) | 1980-10-22 |
| NO760976L (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1976-09-21 |
| FR2304331A1 (fr) | 1976-10-15 |
| PT64922A (de) | 1976-04-01 |
| US4079141A (en) | 1978-03-14 |
| DE2610702A1 (de) | 1976-10-07 |
| LU74590A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1977-01-11 |
| FR2304331B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-07-18 |
| IL49034A (en) | 1980-02-29 |
| FR2346002A1 (fr) | 1977-10-28 |
| FR2346002B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-03-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |