DE2243961A1 - Verfahren zur herstellung von analgetischen verbindungen - Google Patents
Verfahren zur herstellung von analgetischen verbindungenInfo
- Publication number
- DE2243961A1 DE2243961A1 DE2243961A DE2243961A DE2243961A1 DE 2243961 A1 DE2243961 A1 DE 2243961A1 DE 2243961 A DE2243961 A DE 2243961A DE 2243961 A DE2243961 A DE 2243961A DE 2243961 A1 DE2243961 A1 DE 2243961A1
- Authority
- DE
- Germany
- Prior art keywords
- compound
- formula
- hydrogen
- compounds
- stage
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims description 188
- 238000000034 method Methods 0.000 title claims description 45
- 230000000202 analgesic effect Effects 0.000 title description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 90
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 32
- -1 cinnamoyl Chemical group 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 239000003960 organic solvent Substances 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 238000010992 reflux Methods 0.000 claims description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 21
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000001033 ether group Chemical group 0.000 claims description 11
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims 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 claims description 10
- 238000001816 cooling Methods 0.000 claims description 9
- 239000012024 dehydrating agents Substances 0.000 claims description 9
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 9
- 150000003512 tertiary amines Chemical class 0.000 claims description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 8
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 7
- 150000003891 oxalate salts Chemical class 0.000 claims description 7
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical group ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 7
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 6
- 239000012279 sodium borohydride Substances 0.000 claims description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 238000003776 cleavage reaction Methods 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 230000020176 deacylation Effects 0.000 claims description 2
- 238000005947 deacylation reaction Methods 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 8
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- LUMVCLJFHCTMCV-UHFFFAOYSA-M potassium;hydroxide;hydrate Chemical compound O.[OH-].[K+] LUMVCLJFHCTMCV-UHFFFAOYSA-M 0.000 claims 1
- JBJWASZNUJCEKT-UHFFFAOYSA-M sodium;hydroxide;hydrate Chemical compound O.[OH-].[Na+] JBJWASZNUJCEKT-UHFFFAOYSA-M 0.000 claims 1
- 239000000243 solution Substances 0.000 description 62
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 37
- 239000003921 oil Substances 0.000 description 34
- 238000004458 analytical method Methods 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 26
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 26
- 238000002329 infrared spectrum Methods 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- 239000010410 layer Substances 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 239000012458 free base Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 8
- 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 8
- 239000003208 petroleum Substances 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000003887 narcotic antagonist Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000000730 antalgic agent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 6
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 230000003042 antagnostic effect Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 238000006257 total synthesis reaction Methods 0.000 description 5
- 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
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 4
- 239000008896 Opium Substances 0.000 description 4
- 230000001270 agonistic effect Effects 0.000 description 4
- 229930013930 alkaloid Natural products 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 229940035676 analgesics Drugs 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229960005181 morphine Drugs 0.000 description 4
- 229960001027 opium Drugs 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DTVODKGBEXBXFW-BHIFYINESA-N (-)-3-methoxy butorphanol Chemical compound C([C@@]12C3=CC(OC)=CC=C3C[C@@]3([C@@]1(CCCC2)O)[H])CN3CC1CCC1 DTVODKGBEXBXFW-BHIFYINESA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- 239000004593 Epoxy Substances 0.000 description 3
- 239000005639 Lauric acid Substances 0.000 description 3
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
- 229960003878 haloperidol Drugs 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003533 narcotic effect Effects 0.000 description 3
- 229960005118 oxymorphone Drugs 0.000 description 3
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 229960001367 tartaric acid Drugs 0.000 description 3
- 150000003892 tartrate salts Chemical class 0.000 description 3
- YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 description 2
- SVZZBABSMGVXHM-LZWOXQAQSA-N (1R,9R,10R)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-6-ol Chemical compound C1CCC[C@H]2[C@]3([H])NCC[C@@]21C1=CC=CC(O)=C1C3 SVZZBABSMGVXHM-LZWOXQAQSA-N 0.000 description 2
- STBZIDOIKQNFCQ-NRRUETGQSA-N (1S,10S)-17-(cyclopropylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol Chemical compound OC=1C=CC=2CC3[C@@]4(CCCC[C@@]4(C=2C=1)CCN3CC1CC1)O STBZIDOIKQNFCQ-NRRUETGQSA-N 0.000 description 2
- RHCCVERKZAOESA-IXDOHACOSA-N (1S,9R,10S)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@]2(O)CCCC3 RHCCVERKZAOESA-IXDOHACOSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000009120 supportive therapy Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
-
- 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
- C07D221/28—Morphinans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (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)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17883771A | 1971-09-08 | 1971-09-08 | |
| US00217633A US3819635A (en) | 1971-09-08 | 1972-01-13 | 14-hydroxymorphinan derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2243961A1 true DE2243961A1 (de) | 1973-04-05 |
| DE2243961C2 DE2243961C2 (en, 2012) | 1988-07-21 |
Family
ID=26874723
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2243961A Granted DE2243961A1 (de) | 1971-09-08 | 1972-09-07 | Verfahren zur herstellung von analgetischen verbindungen |
| DE2265256A Expired DE2265256C2 (de) | 1971-09-08 | 1972-09-07 | Morphinanderivate und Verfahren zu deren Herstellung |
| DE2265255A Expired DE2265255C2 (de) | 1971-09-08 | 1972-09-07 | 2-Aminoäthylhexahydrophenanthren-Derivate und deren Säureadditionssalze |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2265256A Expired DE2265256C2 (de) | 1971-09-08 | 1972-09-07 | Morphinanderivate und Verfahren zu deren Herstellung |
| DE2265255A Expired DE2265255C2 (de) | 1971-09-08 | 1972-09-07 | 2-Aminoäthylhexahydrophenanthren-Derivate und deren Säureadditionssalze |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US3819635A (en, 2012) |
| JP (1) | JPS5310596B2 (en, 2012) |
| AU (1) | AU470102B2 (en, 2012) |
| BE (1) | BE788478A (en, 2012) |
| CA (1) | CA999578A (en, 2012) |
| CH (1) | CH590845A5 (en, 2012) |
| CY (1) | CY980A (en, 2012) |
| DD (1) | DD100255A5 (en, 2012) |
| DE (3) | DE2243961A1 (en, 2012) |
| DK (1) | DK141624B (en, 2012) |
| FR (1) | FR2154481B1 (en, 2012) |
| GB (2) | GB1412130A (en, 2012) |
| HK (1) | HK2679A (en, 2012) |
| IE (2) | IE36687B1 (en, 2012) |
| KE (1) | KE2911A (en, 2012) |
| MY (1) | MY7900027A (en, 2012) |
| NL (1) | NL162072C (en, 2012) |
| SE (2) | SE398877B (en, 2012) |
| YU (1) | YU45099B (en, 2012) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3910920A (en) * | 1973-11-07 | 1975-10-07 | Bristol Myers Co | 3,14,17-Substituted-6,7-tetramethylenemorphinans |
| US3980641A (en) * | 1975-07-31 | 1976-09-14 | Bristol-Myers Company | Process for the preparation of 14-hydroxymorphinans |
| US4017497A (en) * | 1975-11-18 | 1977-04-12 | Bristol-Myers Company | Process for the preparation of 14-hydroxymorphinan derivatives |
| US4052389A (en) * | 1976-03-23 | 1977-10-04 | Bristol-Myers Company | Derivatives of 9,10-dihydroxy-1-(p-alkoxybenzyl)-perhydroisoquinoline oxazine-3-one |
| US4139534A (en) * | 1977-02-17 | 1979-02-13 | Bristol-Myers Company | Process for the preparation of 14-hydroxymorphinan derivatives |
| JPS52136176A (en) * | 1976-03-23 | 1977-11-14 | Bristol Myers Co | Method of improving 144hydroxymorphinan derivatives |
| US4058531A (en) * | 1976-03-23 | 1977-11-15 | Bristol-Myers Company | Process for the preparation of 14-hydroxymorphinan derivatives |
| GB1587831A (en) * | 1977-03-23 | 1981-04-08 | Reckitt & Colmann Prod Ltd | Morphine derivatives |
| GB1593191A (en) * | 1977-03-23 | 1981-07-15 | Reckitt & Colmann Prod Ltd | Derivatives of morphine |
| US4115389A (en) * | 1977-05-02 | 1978-09-19 | Bristol-Myers Company | Process of N-demethylating (-)-1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline |
| US4338320A (en) * | 1978-11-15 | 1982-07-06 | The Board Of Regents Of The University Of Nebraska | Esters of 6'-hydroxycinchonine, and a method of treating arrythmia with them |
| US4228285A (en) * | 1979-02-28 | 1980-10-14 | Bristol-Myers Company | 14-Hydroxy-6-oxamorphinans and 14-hydroxy-6-oxaisomorphinans |
| US4272540A (en) * | 1979-04-24 | 1981-06-09 | Sisa, Incorporated | 14-Methoxymorphinan-6-one compounds and therapeutic methods of treating pain and drug dependence with them |
| US4322427A (en) * | 1981-04-16 | 1982-03-30 | Bristol-Myers Company | Analgetic compositions and methods of use |
| DE69414085T2 (de) * | 1993-07-19 | 1999-03-18 | Toray Industries, Inc., Tokio/Tokyo | Wirkstoff zum schutze von gehirnzellen |
| DE69424853T2 (de) * | 1993-07-23 | 2000-10-05 | Toray Industries, Inc. | Morphinan-derivate und ihre medizinische verwendung |
| CZ281174B6 (cs) * | 1993-08-13 | 1996-07-17 | Galena, A.S. | Způsob přípravy 3,14ß-dihydroxy-17-normorfinanu |
| AU753278B2 (en) | 1998-02-25 | 2002-10-10 | Abbott Laboratories | Butorphanol sustained release formulations |
| US20040167164A1 (en) * | 1998-05-05 | 2004-08-26 | Jose Pozuelo | Compositions and methods for treating particular chemical addictions and mental illnesses |
| US7923454B2 (en) | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US7501433B2 (en) * | 2002-05-17 | 2009-03-10 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| WO2003097608A2 (en) | 2002-05-17 | 2003-11-27 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US8017622B2 (en) * | 2003-05-16 | 2011-09-13 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN103073496B (zh) * | 2013-02-18 | 2015-08-26 | 苏州立新制药有限公司 | 右美沙芬的制备方法 |
| JP6464181B2 (ja) | 2014-10-14 | 2019-02-06 | 久光製薬株式会社 | 貼付剤 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3166559A (en) * | 1965-01-19 | J-lower alkoxy-x-phenyloxy-ix-hydroxy- | ||
| GB1028407A (en) * | 1962-04-06 | 1966-05-04 | Shionogi & Co | Improvements in or relating to morphinan derivatives and their preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1362540A (fr) * | 1963-04-05 | 1964-06-05 | Shionogi & Co | Dérivés n substitués du morphinane et leur production |
-
0
- BE BE788478D patent/BE788478A/xx not_active IP Right Cessation
-
1972
- 1972-01-13 US US00217633A patent/US3819635A/en not_active Expired - Lifetime
- 1972-08-23 CA CA150,036A patent/CA999578A/en not_active Expired
- 1972-09-01 AU AU46228/72A patent/AU470102B2/en not_active Expired
- 1972-09-06 DK DK440172AA patent/DK141624B/da not_active IP Right Cessation
- 1972-09-06 IE IE1213/72A patent/IE36687B1/xx unknown
- 1972-09-06 IE IE103/76A patent/IE36688B1/xx unknown
- 1972-09-06 SE SE7211522A patent/SE398877B/xx unknown
- 1972-09-07 CH CH1315472A patent/CH590845A5/xx not_active IP Right Cessation
- 1972-09-07 DE DE2243961A patent/DE2243961A1/de active Granted
- 1972-09-07 GB GB1057175A patent/GB1412130A/en not_active Expired
- 1972-09-07 JP JP8916172A patent/JPS5310596B2/ja not_active Expired
- 1972-09-07 CY CY980A patent/CY980A/xx unknown
- 1972-09-07 DE DE2265256A patent/DE2265256C2/de not_active Expired
- 1972-09-07 FR FR7231816A patent/FR2154481B1/fr not_active Expired
- 1972-09-07 NL NL7212176.A patent/NL162072C/xx not_active IP Right Cessation
- 1972-09-07 DE DE2265255A patent/DE2265255C2/de not_active Expired
- 1972-09-07 YU YU227772A patent/YU45099B/sh unknown
- 1972-09-07 GB GB4161972A patent/GB1412129A/en not_active Expired
- 1972-09-08 DD DD165557A patent/DD100255A5/xx unknown
-
1975
- 1975-06-02 SE SE7506292A patent/SE403286B/xx not_active IP Right Cessation
-
1978
- 1978-12-24 KE KE2911A patent/KE2911A/xx unknown
-
1979
- 1979-01-11 HK HK26/79A patent/HK2679A/xx unknown
- 1979-12-30 MY MY27/79A patent/MY7900027A/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3166559A (en) * | 1965-01-19 | J-lower alkoxy-x-phenyloxy-ix-hydroxy- | ||
| GB1028407A (en) * | 1962-04-06 | 1966-05-04 | Shionogi & Co | Improvements in or relating to morphinan derivatives and their preparation |
Non-Patent Citations (1)
| Title |
|---|
| Tetrahedron 24, S.6185, 1968 * |
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