CH558362A - Verfahren zur herstellung von endoaethano-tetrahydrothebainen bzw. -oripavinen. - Google Patents
Verfahren zur herstellung von endoaethano-tetrahydrothebainen bzw. -oripavinen.Info
- Publication number
- CH558362A CH558362A CH861766A CH861766A CH558362A CH 558362 A CH558362 A CH 558362A CH 861766 A CH861766 A CH 861766A CH 861766 A CH861766 A CH 861766A CH 558362 A CH558362 A CH 558362A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- endoethano
- hydroxy
- formula
- propyl
- Prior art date
Links
- -1 CnH2n + 1 CO- Chemical group 0.000 claims abstract description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000002723 alicyclic group Chemical group 0.000 claims abstract description 7
- 230000001476 alcoholic effect Effects 0.000 claims abstract description 6
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000004429 atom Chemical group 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 26
- 239000000047 product Substances 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- QKQQEIVDLRUZRP-UHFFFAOYSA-N northebaine Natural products COC1=CC=C2C(NCC3)CC4=CC=C(OC)C5=C4C23C1O5 QKQQEIVDLRUZRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002902 organometallic compounds Chemical class 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 150000002900 organolithium compounds Chemical class 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 238000005661 deetherification reaction Methods 0.000 claims 2
- 150000001266 acyl halides Chemical class 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 abstract description 3
- 125000003118 aryl group Chemical group 0.000 abstract 2
- ZKLXUUYLEHCAMF-UUWFMWQGSA-N Oripavine Chemical class C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ZKLXUUYLEHCAMF-UUWFMWQGSA-N 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 150000001450 anions Chemical class 0.000 abstract 1
- 125000004104 aryloxy group Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 abstract 1
- 229940051808 oripavine derivative analgesics Drugs 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 abstract 1
- 229930003945 thebaine Natural products 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 238000003756 stirring Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000010410 layer Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- FRLKJAAPFJROFZ-UHFFFAOYSA-N N-nororipavine Natural products COC1=CC=C2C(NCC3)CC4=CC=C(O)C5=C4C23C1O5 FRLKJAAPFJROFZ-UHFFFAOYSA-N 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- RVJQWONQPCTLDL-SSTWWWIQSA-N (4r,4ar,7s,7ar,12bs)-7,9-dimethoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2CC[C@@H]3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 RVJQWONQPCTLDL-SSTWWWIQSA-N 0.000 description 1
- KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical class CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 1
- BSPCSKHALVHRSR-UHFFFAOYSA-N 2-chlorobutane Chemical compound CCC(C)Cl BSPCSKHALVHRSR-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 102220501443 Cytosolic iron-sulfur assembly component 3_C27N_mutation Human genes 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 230000006179 O-acylation Effects 0.000 description 1
- ZKLXUUYLEHCAMF-UHFFFAOYSA-N Oripavine Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(O)C5=C4C23C1O5 ZKLXUUYLEHCAMF-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 101100072646 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) INO4 gene Proteins 0.000 description 1
- CDKFWIMBZAUBRS-UHFFFAOYSA-M [I-].CC[Mg+] Chemical compound [I-].CC[Mg+] CDKFWIMBZAUBRS-UHFFFAOYSA-M 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 125000005741 alkyl alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 230000021962 pH elevation Effects 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 239000001472 potassium tartrate Substances 0.000 description 1
- 229940111695 potassium tartrate Drugs 0.000 description 1
- 235000011005 potassium tartrates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/09—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems
- C07D489/10—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14
- C07D489/12—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14 the bridge containing only two carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH359670A CH551415A (de) | 1965-06-15 | 1966-06-15 | Verfahren zur herstellung von heterocyclischen verbindungen. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB25289/65A GB1136214A (en) | 1965-06-15 | 1965-06-15 | Thebaine and oripavine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH558362A true CH558362A (de) | 1975-01-31 |
Family
ID=10225305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH861766A CH558362A (de) | 1965-06-15 | 1966-06-15 | Verfahren zur herstellung von endoaethano-tetrahydrothebainen bzw. -oripavinen. |
Country Status (14)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003095458A1 (en) * | 2002-05-10 | 2003-11-20 | Reckitt Benckiser Healthcare (Uk) Limited | Microbial n- and o-demethylation of a thebaine derivative |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2554816B1 (fr) * | 1983-11-16 | 1986-09-26 | Sanofi Sa | Nouveau derive de la nororipavine presentant a la fois une activite agoniste et antagoniste des recepteurs morphiniques |
| KR100204659B1 (ko) * | 1996-05-28 | 1999-06-15 | 강재헌 | 신규한 부프레노핀계 진통제용 화합물 |
| RU2138502C1 (ru) * | 1999-03-29 | 1999-09-27 | Закрытое акционерное общество "РМА-Фарм" | Способ получения 17-циклопропилметил-6,14-эндо-этано-7-(2-гидрокси-3,3-диметилбут-2-ил)тетр агидро-17-норорипавина |
| AUPQ968300A0 (en) | 2000-08-25 | 2000-09-21 | Glaxo Wellcome Australia Ltd | Chemical methods |
| GB0421687D0 (en) † | 2004-09-30 | 2004-11-03 | Johnson Matthey Plc | Preparation of opiate analgesics |
| WO2006091885A2 (en) | 2005-02-24 | 2006-08-31 | Dr Pharma Nova, Llc | A registry method and control system for dea schedule ii-v medicines |
| DE102006054731B4 (de) | 2006-11-21 | 2013-02-28 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System zur Verabreichung des Wirkstoffs Buprenorphin und Verwendung desselben in der Schmerztherapie |
| ME01665B (me) | 2008-07-30 | 2014-09-20 | Purdue Pharma Lp | Analozi buprenorfina |
| AU2009300386B2 (en) | 2008-09-30 | 2015-07-02 | SpecGx LLC | Processes for the alkylation of norbuprenorphine with reduced impurity formation |
| AU2010239059B2 (en) | 2009-04-24 | 2016-06-09 | Brock University | Processes for the preparation of morphinane and morphinone compounds |
| GB201111775D0 (en) | 2011-07-08 | 2011-08-24 | Univ Bath | Compounds and uses thereof |
| WO2013088254A1 (en) | 2011-12-12 | 2013-06-20 | Lts Lohmann Therapie-Systeme Ag | Transdermal delivery system comprising buprenorphine |
| SG10201703964TA (en) | 2012-07-26 | 2017-06-29 | Camurus Ab | Opioid formulations |
| EP3326613A1 (en) | 2012-07-26 | 2018-05-30 | Camurus AB | Opioid formulations |
| JP6317755B2 (ja) * | 2012-12-07 | 2018-04-25 | パーデュー、ファーマ、リミテッド、パートナーシップ | オピオイド受容体モジュレーターとしてのブプレノルフィン類似体 |
| HK1222135A1 (zh) | 2013-06-04 | 2017-06-23 | Lts Lohmann Therapie-Systeme Ag | 透皮遞送系統 |
| US20250154160A1 (en) | 2021-12-16 | 2025-05-15 | Arevipharma Gmbh | Method of making buprenorphine and precursor compounds thereof |
-
1965
- 1965-06-15 GB GB25289/65A patent/GB1136214A/en not_active Expired
-
1966
- 1966-06-10 NO NO163395A patent/NO119590B/no unknown
- 1966-06-13 LU LU51306A patent/LU51306A1/xx unknown
- 1966-06-13 FI FI661555A patent/FI49724C/fi active
- 1966-06-14 BR BR180359/66A patent/BR6680359D0/pt unknown
- 1966-06-14 SE SE08101/66A patent/SE325276B/xx unknown
- 1966-06-14 NL NL6608255A patent/NL6608255A/xx unknown
- 1966-06-14 ES ES0327925A patent/ES327925A1/es not_active Expired
- 1966-06-15 CH CH861766A patent/CH558362A/de not_active IP Right Cessation
- 1966-06-15 FR FR65560A patent/FR6395M/fr not_active Expired
- 1966-06-15 BE BE682551D patent/BE682551A/xx not_active IP Right Cessation
- 1966-06-15 DE DE19661620206 patent/DE1620206A1/de active Pending
- 1966-06-15 AT AT571566A patent/AT272530B/de active
- 1966-06-15 DK DK307766AA patent/DK115926B/da unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003095458A1 (en) * | 2002-05-10 | 2003-11-20 | Reckitt Benckiser Healthcare (Uk) Limited | Microbial n- and o-demethylation of a thebaine derivative |
| US7267968B2 (en) | 2002-05-10 | 2007-09-11 | Reckitt Benekiser Healthcare (Uk) Limited | Microbial n-and o-demethylation of a thebaine derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| FI49724C (fi) | 1975-09-10 |
| SE325276B (enrdf_load_stackoverflow) | 1970-06-29 |
| GB1136214A (en) | 1968-12-11 |
| NO119590B (enrdf_load_stackoverflow) | 1970-06-08 |
| LU51306A1 (enrdf_load_stackoverflow) | 1966-08-16 |
| NL6608255A (enrdf_load_stackoverflow) | 1966-12-16 |
| AT272530B (de) | 1969-07-10 |
| FR6395M (enrdf_load_stackoverflow) | 1968-10-21 |
| BR6680359D0 (pt) | 1973-12-26 |
| FI49724B (enrdf_load_stackoverflow) | 1975-06-02 |
| DE1620206A1 (de) | 1970-03-19 |
| DK115926B (da) | 1969-11-24 |
| BE682551A (enrdf_load_stackoverflow) | 1966-11-14 |
| ES327925A1 (es) | 1967-04-01 |
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Legal Events
| Date | Code | Title | Description |
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| PL | Patent ceased |