NO328154B1 - Teknisk syntesemetode for fremstilling av Tropenol samt anvendelse av slike forbindelser for fremstilling av terapeutisk virksomme forbindelser - Google Patents
Teknisk syntesemetode for fremstilling av Tropenol samt anvendelse av slike forbindelser for fremstilling av terapeutisk virksomme forbindelser Download PDFInfo
- Publication number
- NO328154B1 NO328154B1 NO20035633A NO20035633A NO328154B1 NO 328154 B1 NO328154 B1 NO 328154B1 NO 20035633 A NO20035633 A NO 20035633A NO 20035633 A NO20035633 A NO 20035633A NO 328154 B1 NO328154 B1 NO 328154B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- optionally
- acid addition
- tropenol
- salts
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title description 11
- 238000001308 synthesis method Methods 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims description 53
- 239000002253 acid Substances 0.000 claims description 43
- 239000002904 solvent Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 24
- 239000011701 zinc Substances 0.000 claims description 22
- 229910052725 zinc Inorganic materials 0.000 claims description 21
- 229960000257 tiotropium bromide Drugs 0.000 claims description 20
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 17
- 239000002184 metal Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 15
- 150000004677 hydrates Chemical class 0.000 claims description 9
- 239000007858 starting material Substances 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- 230000003213 activating effect Effects 0.000 claims description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 229960001361 ipratropium bromide Drugs 0.000 claims description 6
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 claims description 6
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 claims description 5
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 claims description 5
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 5
- 239000007825 activation reagent Substances 0.000 claims description 5
- 229960002646 scopolamine Drugs 0.000 claims description 5
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims description 5
- 125000001272 (C1-C4)-alkylene-phenyl group Chemical group 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 4
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 3
- 150000001879 copper Chemical class 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- FIMXSEMBHGTNKT-UPGAHCIJSA-N scopine Chemical class C([C@@H]1N2C)C(O)C[C@@H]2[C@@H]2[C@H]1O2 FIMXSEMBHGTNKT-UPGAHCIJSA-N 0.000 claims description 2
- 101100115215 Caenorhabditis elegans cul-2 gene Proteins 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- -1 compounds Tiotropium bromide Chemical class 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 239000002585 base Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229940102396 methyl bromide Drugs 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- FVEJUHUCFCAYRP-UHFFFAOYSA-N 2-hydroxy-2,2-dithiophen-2-ylacetic acid Chemical compound C=1C=CSC=1C(O)(C(=O)O)C1=CC=CS1 FVEJUHUCFCAYRP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 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
- 150000004679 hydroxides Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003751 zinc Chemical class 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FIMXSEMBHGTNKT-UHFFFAOYSA-N Scopine Natural products CN1C2CC(O)CC1C1C2O1 FIMXSEMBHGTNKT-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- IFCAMEQHKHEHBS-UHFFFAOYSA-N [6-acetyloxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]methyl acetate Chemical compound C=1C=CC=CC=1COC1C(OCC=2C=CC=CC=2)C(COC(=O)C)OC(OC(C)=O)C1OCC1=CC=CC=C1 IFCAMEQHKHEHBS-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
- 239000013543 active substance Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 239000006227 byproduct Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- SYHWYWHVEQQDMO-UHFFFAOYSA-N methyl 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C=1C=CSC=1C(O)(C(=O)OC)C1=CC=CS1 SYHWYWHVEQQDMO-UHFFFAOYSA-N 0.000 description 1
- GSJFXBNYJCXDGI-UHFFFAOYSA-N methyl 2-hydroxyacetate Chemical compound COC(=O)CO GSJFXBNYJCXDGI-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000004682 monohydrates Chemical class 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960004499 scopolamine hydrobromide Drugs 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- MQLXPRBEAHBZTK-SEINRUQRSA-M tiotropium bromide hydrate Chemical compound O.[Br-].C[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 MQLXPRBEAHBZTK-SEINRUQRSA-M 0.000 description 1
- JACRWUWPXAESPB-UHFFFAOYSA-N tropic acid Chemical compound OCC(C(O)=O)C1=CC=CC=C1 JACRWUWPXAESPB-UHFFFAOYSA-N 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Lock And Its Accessories (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10131200 | 2001-06-28 | ||
| PCT/EP2002/006290 WO2003002562A1 (de) | 2001-06-28 | 2002-06-08 | Technische syntheseverfahren zur herstellung von tropenol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20035633D0 NO20035633D0 (no) | 2003-12-17 |
| NO328154B1 true NO328154B1 (no) | 2009-12-21 |
Family
ID=7689774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20035633A NO328154B1 (no) | 2001-06-28 | 2003-12-17 | Teknisk syntesemetode for fremstilling av Tropenol samt anvendelse av slike forbindelser for fremstilling av terapeutisk virksomme forbindelser |
Country Status (41)
| Country | Link |
|---|---|
| US (1) | US6610849B2 (ru) |
| EP (3) | EP1475379B1 (ru) |
| JP (2) | JP4485192B2 (ru) |
| KR (3) | KR100866272B1 (ru) |
| CN (2) | CN1982309B (ru) |
| AR (1) | AR039056A1 (ru) |
| AT (3) | ATE359285T1 (ru) |
| AU (2) | AU2002257820B2 (ru) |
| BG (2) | BG66398B1 (ru) |
| BR (1) | BR0210664B1 (ru) |
| CA (1) | CA2451573C (ru) |
| CO (1) | CO5650166A2 (ru) |
| CY (1) | CY1107681T1 (ru) |
| CZ (1) | CZ296187B6 (ru) |
| DE (2) | DE50203015D1 (ru) |
| DK (3) | DK1808435T3 (ru) |
| EA (2) | EA006393B1 (ru) |
| EC (1) | ECSP034927A (ru) |
| EE (1) | EE05403B1 (ru) |
| EG (1) | EG23203A (ru) |
| ES (3) | ES2374981T3 (ru) |
| HK (2) | HK1068613A1 (ru) |
| HR (2) | HRP20031085B1 (ru) |
| HU (2) | HU230036B1 (ru) |
| IL (2) | IL159239A0 (ru) |
| ME (1) | MEP42608A (ru) |
| MX (1) | MXPA03011516A (ru) |
| MY (1) | MY122932A (ru) |
| NO (1) | NO328154B1 (ru) |
| NZ (2) | NZ541395A (ru) |
| PE (1) | PE20030123A1 (ru) |
| PL (1) | PL209520B1 (ru) |
| PT (2) | PT1475379E (ru) |
| RS (1) | RS50436B (ru) |
| SA (1) | SA02230194B1 (ru) |
| SI (2) | SI1475379T1 (ru) |
| SK (1) | SK288022B6 (ru) |
| TW (1) | TW574220B (ru) |
| UA (2) | UA76761C2 (ru) |
| WO (1) | WO2003002562A1 (ru) |
| ZA (1) | ZA200308895B (ru) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10141377A1 (de) | 2001-08-23 | 2003-03-13 | Boehringer Ingelheim Pharma | Aufstreuverfahren zur Herstellung von Pulverformulierungen |
| US6747153B2 (en) * | 2002-05-31 | 2004-06-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Industrial process for preparing tropenol |
| US20090162562A1 (en) * | 2007-12-24 | 2009-06-25 | Bangalore Aswatha Nagaraj | Methods for Applying Thermal Barrier Coating Systems |
| JP6087492B2 (ja) * | 2008-01-10 | 2017-03-01 | ジェネリクス・［ユーケー］・リミテッド | スコピンエステルを調製するための新規プロセス |
| CA2931876A1 (en) | 2009-08-07 | 2011-02-10 | Generics [Uk] Limited | Anhydrate of tiotropium bromide |
| WO2011015884A1 (en) | 2009-08-07 | 2011-02-10 | Generics [Uk] Limited | Process to prepare scopine esters |
| CN102351856B (zh) * | 2011-08-24 | 2013-05-01 | 商丘市韶华药业有限公司 | 一种α-托品醇的纯化方法 |
| ITRM20110508A1 (it) | 2011-09-27 | 2013-03-28 | Lusochimica Spa | Processo per la preparazione degli esteri della scopina. |
| RS55996B1 (sr) * | 2011-12-22 | 2017-09-29 | Cerbios-Pharma S A | Kontinuirani postupak za alkilaciju cikličnih tercijarnih amina |
| CN113292574B (zh) * | 2020-02-21 | 2022-05-03 | 四川大学 | 一类手性多环的托品烷化合物及其制备方法和用途 |
| CN111269226B (zh) * | 2020-04-13 | 2021-09-21 | 石家庄四药有限公司 | 异丙托溴铵的合成方法 |
| CN113264929B (zh) * | 2021-05-02 | 2023-10-10 | 润生药业有限公司 | 一种噻托溴铵的制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3931041C2 (de) * | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| WO1995028401A1 (en) * | 1994-04-19 | 1995-10-26 | Neurosearch A/S | Tropane-2-aldoxine derivatives as neurotransmitter reuptake inhibitors |
| DE19515625C2 (de) * | 1995-04-28 | 1998-02-19 | Boehringer Ingelheim Kg | Verfahren zur Herstellung von enantiomerenreinen Tropasäureestern |
-
2002
- 2002-06-03 US US10/160,702 patent/US6610849B2/en not_active Expired - Lifetime
- 2002-06-08 EA EA200301292A patent/EA006393B1/ru not_active IP Right Cessation
- 2002-06-08 EP EP04018550A patent/EP1475379B1/de not_active Revoked
- 2002-06-08 DK DK07101821.2T patent/DK1808435T3/da active
- 2002-06-08 ES ES07101821T patent/ES2374981T3/es not_active Expired - Lifetime
- 2002-06-08 EP EP07101821A patent/EP1808435B1/de not_active Expired - Lifetime
- 2002-06-08 JP JP2003508943A patent/JP4485192B2/ja not_active Expired - Lifetime
- 2002-06-08 IL IL15923902A patent/IL159239A0/xx unknown
- 2002-06-08 SK SK66-2004A patent/SK288022B6/sk not_active IP Right Cessation
- 2002-06-08 CN CN2006101604057A patent/CN1982309B/zh not_active Expired - Lifetime
- 2002-06-08 ES ES04018550T patent/ES2285318T3/es not_active Expired - Lifetime
- 2002-06-08 CA CA2451573A patent/CA2451573C/en not_active Expired - Fee Related
- 2002-06-08 HU HU0400332A patent/HU230036B1/hu unknown
- 2002-06-08 AT AT04018550T patent/ATE359285T1/de active
- 2002-06-08 DK DK04018550T patent/DK1475379T3/da active
- 2002-06-08 WO PCT/EP2002/006290 patent/WO2003002562A1/de active Application Filing
- 2002-06-08 DE DE50203015T patent/DE50203015D1/de not_active Expired - Lifetime
- 2002-06-08 MX MXPA03011516A patent/MXPA03011516A/es active IP Right Grant
- 2002-06-08 DE DE50209948T patent/DE50209948D1/de not_active Expired - Lifetime
- 2002-06-08 EA EA200501081A patent/EA009808B1/ru not_active IP Right Cessation
- 2002-06-08 AT AT02727610T patent/ATE294801T1/de active
- 2002-06-08 KR KR1020037017010A patent/KR100866272B1/ko active IP Right Grant
- 2002-06-08 PT PT04018550T patent/PT1475379E/pt unknown
- 2002-06-08 RS YUP-1011/03A patent/RS50436B/sr unknown
- 2002-06-08 CN CNB028128672A patent/CN1288154C/zh not_active Expired - Lifetime
- 2002-06-08 NZ NZ541395A patent/NZ541395A/en not_active IP Right Cessation
- 2002-06-08 SI SI200230540T patent/SI1475379T1/sl unknown
- 2002-06-08 PT PT02727610T patent/PT1404673E/pt unknown
- 2002-06-08 DK DK02727610T patent/DK1404673T3/da active
- 2002-06-08 CZ CZ20040149A patent/CZ296187B6/cs not_active IP Right Cessation
- 2002-06-08 AT AT07101821T patent/ATE527257T1/de active
- 2002-06-08 EE EEP200400045A patent/EE05403B1/xx not_active IP Right Cessation
- 2002-06-08 ES ES02727610T patent/ES2242022T3/es not_active Expired - Lifetime
- 2002-06-08 ME MEP-426/08A patent/MEP42608A/xx unknown
- 2002-06-08 SI SI200230153T patent/SI1404673T1/xx unknown
- 2002-06-08 KR KR1020087014692A patent/KR100886342B1/ko active IP Right Grant
- 2002-06-08 PL PL366942A patent/PL209520B1/pl unknown
- 2002-06-08 AU AU2002257820A patent/AU2002257820B2/en not_active Expired
- 2002-06-08 EP EP02727610A patent/EP1404673B1/de not_active Expired - Lifetime
- 2002-06-08 NZ NZ530770A patent/NZ530770A/en not_active IP Right Cessation
- 2002-06-08 HU HU1400554A patent/HU230379B1/hu unknown
- 2002-06-08 BR BRPI0210664-7B1A patent/BR0210664B1/pt active IP Right Grant
- 2002-06-25 PE PE2002000553A patent/PE20030123A1/es not_active Application Discontinuation
- 2002-06-26 EG EG2002060738A patent/EG23203A/xx active
- 2002-06-26 MY MYPI20022420A patent/MY122932A/en unknown
- 2002-06-26 TW TW91114026A patent/TW574220B/zh not_active IP Right Cessation
- 2002-06-28 AR ARP020102453A patent/AR039056A1/es active Pending
- 2002-07-10 SA SA2230194A patent/SA02230194B1/ar unknown
- 2002-08-06 UA UA2004010605A patent/UA76761C2/ru unknown
-
2003
- 2003-03-28 KR KR10-2003-0019708A patent/KR100530661B1/ko not_active IP Right Cessation
- 2003-11-14 ZA ZA200308895A patent/ZA200308895B/en unknown
- 2003-12-08 IL IL159239A patent/IL159239A/en active IP Right Grant
- 2003-12-17 NO NO20035633A patent/NO328154B1/no not_active IP Right Cessation
- 2003-12-17 BG BG108462A patent/BG66398B1/bg active Active
- 2003-12-23 CO CO03112174A patent/CO5650166A2/es active IP Right Grant
- 2003-12-24 HR HR20031085A patent/HRP20031085B1/xx not_active IP Right Cessation
- 2003-12-24 EC EC2003004927A patent/ECSP034927A/es unknown
-
2005
- 2005-01-29 HK HK05100781A patent/HK1068613A1/xx not_active IP Right Cessation
-
2006
- 2006-03-09 UA UAA200602562A patent/UA86031C2/ru unknown
-
2007
- 2007-06-21 CY CY20071100822T patent/CY1107681T1/el unknown
- 2007-10-31 HK HK07111732.3A patent/HK1103404A1/xx not_active IP Right Cessation
-
2008
- 2008-04-08 AU AU2008201565A patent/AU2008201565B2/en not_active Expired
-
2009
- 2009-02-23 HR HR20090110A patent/HRP20090110A2/xx not_active Application Discontinuation
- 2009-10-13 JP JP2009236400A patent/JP2010043116A/ja active Pending
-
2013
- 2013-05-07 BG BG10111461A patent/BG111461A/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008201565B2 (en) | Technical synethesis method for producing Tropenol | |
| CA2433518C (en) | Method for producing the anticholinergic tiotropium bromide | |
| US7321039B2 (en) | Industrial process for preparing tropenol | |
| CA2725704C (en) | Industrial process for preparing tropenol | |
| EP2460803B1 (en) | Method for producing thiabenzoazulene propionic acid derivative | |
| JPH0533707B2 (ru) | ||
| JPH0616666A (ja) | 双環状アミン誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |