CH637929A5 - Process for the preparation of optically active azabicycloalkanes - Google Patents
Process for the preparation of optically active azabicycloalkanes Download PDFInfo
- Publication number
- CH637929A5 CH637929A5 CH1118977A CH1118977A CH637929A5 CH 637929 A5 CH637929 A5 CH 637929A5 CH 1118977 A CH1118977 A CH 1118977A CH 1118977 A CH1118977 A CH 1118977A CH 637929 A5 CH637929 A5 CH 637929A5
- Authority
- CH
- Switzerland
- Prior art keywords
- solution
- mixture
- benzene
- azabicyclo
- acid
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 41
- 238000000034 method Methods 0.000 title claims description 36
- 230000008569 process Effects 0.000 title claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 230
- 239000000203 mixture Substances 0.000 claims description 104
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 98
- 150000001875 compounds Chemical class 0.000 claims description 53
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- UHQOPDGATRGDDD-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound O=C1NC(=O)C2CC12 UHQOPDGATRGDDD-UHFFFAOYSA-N 0.000 claims description 30
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- 241000700159 Rattus Species 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 150000004678 hydrides Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 230000000202 analgesic effect Effects 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 241000699670 Mus sp. Species 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000010 aprotic solvent Substances 0.000 claims description 6
- 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 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 239000000730 antalgic agent Substances 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 229940035676 analgesics Drugs 0.000 claims description 2
- OFYVIGTWSQPCLF-UHFFFAOYSA-N 1-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1=CC(C)=CC=C1C1(CNC2)C2C1 OFYVIGTWSQPCLF-UHFFFAOYSA-N 0.000 claims 2
- VDQQJMHXZCMNMU-UHFFFAOYSA-N 1-phenylpyrrolidine Chemical group C1CCCN1C1=CC=CC=C1 VDQQJMHXZCMNMU-UHFFFAOYSA-N 0.000 claims 1
- VFUGCQKESINERB-UHFFFAOYSA-N 3-(1-methyl-3-propylpyrrolidin-3-yl)phenol Chemical compound C=1C=CC(O)=CC=1C1(CCC)CCN(C)C1 VFUGCQKESINERB-UHFFFAOYSA-N 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000002249 anxiolytic agent Substances 0.000 claims 1
- OFYVIGTWSQPCLF-NWDGAFQWSA-N bicifadine Chemical compound C1=CC(C)=CC=C1[C@@]1(CNC2)[C@H]2C1 OFYVIGTWSQPCLF-NWDGAFQWSA-N 0.000 claims 1
- 229950010365 bicifadine Drugs 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 230000003533 narcotic effect Effects 0.000 claims 1
- 229950004859 profadol Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 139
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 102
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
- 239000013078 crystal Substances 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 238000010992 reflux Methods 0.000 description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- 239000003921 oil Substances 0.000 description 35
- 235000019198 oils Nutrition 0.000 description 35
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 235000019341 magnesium sulphate Nutrition 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 25
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 21
- 239000007788 liquid Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000004202 carbamide Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- 210000002683 foot Anatomy 0.000 description 11
- 150000003949 imides Chemical class 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000008096 xylene Substances 0.000 description 11
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
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- 239000012071 phase Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- 230000005021 gait Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 150000005690 diesters Chemical class 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- HJLHTTJLVALHOP-UHFFFAOYSA-N hexane;hydron;chloride Chemical compound Cl.CCCCCC HJLHTTJLVALHOP-UHFFFAOYSA-N 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000012876 carrier material Substances 0.000 description 5
- 150000001991 dicarboxylic acids Chemical class 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
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- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 4
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- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000000391 magnesium silicate Substances 0.000 description 4
- 229910052919 magnesium silicate Inorganic materials 0.000 description 4
- 235000019792 magnesium silicate Nutrition 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 4
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- 238000012360 testing method Methods 0.000 description 4
- JCBPETKZIGVZRE-SCSAIBSYSA-N (2r)-2-aminobutan-1-ol Chemical compound CC[C@@H](N)CO JCBPETKZIGVZRE-SCSAIBSYSA-N 0.000 description 3
- VLWYROJLUFPLPC-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1=CC(Cl)=CC=C1C1(CNC2)C2C1 VLWYROJLUFPLPC-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
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- 206010010904 Convulsion Diseases 0.000 description 3
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- 230000037396 body weight Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/40—Unsaturated compounds containing halogen
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- 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
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/36—Polyhydroxylic alcohols containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/28—Unsaturated compounds polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/34—Unsaturated compounds containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH209382A CH637931A5 (en) | 1976-09-15 | 1982-04-05 | Process for the preparation of optically active azabicycloalkanes |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72340276A | 1976-09-15 | 1976-09-15 | |
| US05/809,339 US4131611A (en) | 1975-07-31 | 1977-06-23 | Azabicyclohexanes |
| US05/809,341 US4118393A (en) | 1977-06-23 | 1977-06-23 | Phenyl azabicyclohexanones |
| US05/809,340 US4118417A (en) | 1977-06-23 | 1977-06-23 | Process for resolving cis-1-substituted phenyl-1,2-cyclopropanedicarboxylic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH637929A5 true CH637929A5 (en) | 1983-08-31 |
Family
ID=27505564
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1118977A CH637929A5 (en) | 1976-09-15 | 1977-09-13 | Process for the preparation of optically active azabicycloalkanes |
| CH209382A CH637931A5 (en) | 1976-09-15 | 1982-04-05 | Process for the preparation of optically active azabicycloalkanes |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH209382A CH637931A5 (en) | 1976-09-15 | 1982-04-05 | Process for the preparation of optically active azabicycloalkanes |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5337656A (en)van) |
| AR (2) | AR220684A1 (en)van) |
| AT (2) | AT367036B (en)van) |
| AU (1) | AU519620B2 (en)van) |
| BE (1) | BE858683A (en)van) |
| CH (2) | CH637929A5 (en)van) |
| DD (1) | DD133943A5 (en)van) |
| DE (1) | DE2740562A1 (en)van) |
| DK (3) | DK146245C (en)van) |
| FR (1) | FR2375212A1 (en)van) |
| GR (1) | GR72713B (en)van) |
| HU (1) | HU177531B (en)van) |
| NL (1) | NL189041C (en)van) |
| PL (1) | PL115869B1 (en)van) |
| SE (2) | SE435384B (en)van) |
| YU (2) | YU39499B (en)van) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4183857A (en) * | 1978-07-06 | 1980-01-15 | Shell Oil Company | 3-Benzyl-3-azabicyclo(3.1.0)hexane-2,4-dione |
| IL65843A (en) * | 1977-08-11 | 1986-12-31 | American Cyanamid Co | Pharmaceutical compositions for the treatment of depression containing 3-aza-bicyclo(3.1.0)hexane derivatives and certain novel compounds of this type |
| CA1117127A (en) * | 1978-06-27 | 1982-01-26 | Janet A. Day | Derivatives of 3-azabicyclo(3.1.0)hexane and a process for their preparation |
| US4225499A (en) * | 1978-07-06 | 1980-09-30 | Shell Oil Company | Process for preparing 3-azabicyclo(3.1.0)hexane-2-carbonitrile |
| JPS6332100A (ja) * | 1986-07-25 | 1988-02-10 | 東京電力株式会社 | シ−ルド掘進機 |
| JPH0658037B2 (ja) * | 1989-09-01 | 1994-08-03 | 日本鋼管株式会社 | シールド掘進装置 |
| US6372919B1 (en) | 2001-01-11 | 2002-04-16 | Dov Pharmaceutical, Inc. | (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as an anti-depressant agent |
| US6569887B2 (en) | 2001-08-24 | 2003-05-27 | Dov Pharmaceuticals Inc. | (−)-1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as a dopamine-reuptake |
| US20080081834A1 (en) | 2002-07-31 | 2008-04-03 | Lippa Arnold S | Methods and compositions employing bicifadine for treating disability or functional impairment associated with acute pain, chronic pain, or neuropathic disorders |
| RU2007102292A (ru) * | 2004-07-22 | 2008-08-27 | Вайет (Us) | Способ лечения расстройств и заболеваний нервной системы |
| EP1773322A1 (en) * | 2004-07-22 | 2007-04-18 | Wyeth | Method for treating nervous system disorders and conditions |
| US20070043100A1 (en) | 2005-08-16 | 2007-02-22 | Hagen Eric J | Novel polymorphs of azabicyclohexane |
| BRPI0613943B1 (pt) | 2005-07-27 | 2021-06-22 | Otsuka America Pharmaceutical, Inc | Composto, composição farmacêutica o compreendendo, usos de um composto e de uma composição farmacêutica, bem como composição neurobiologicamente ativa |
| US20080045725A1 (en) | 2006-04-28 | 2008-02-21 | Murry Jerry A | Process For The Synthesis of (+) And (-)-1-(3,4-Dichlorophenyl)-3-Azabicyclo[3.1.0]Hexane |
| US8138377B2 (en) | 2006-11-07 | 2012-03-20 | Dov Pharmaceutical, Inc. | Arylbicyclo[3.1.0]hexylamines and methods and compositions for their preparation and use |
| US9133159B2 (en) | 2007-06-06 | 2015-09-15 | Neurovance, Inc. | 1-heteroaryl-3-azabicyclo[3.1.0]hexanes, methods for their preparation and their use as medicaments |
| US20140206740A1 (en) | 2011-07-30 | 2014-07-24 | Neurovance, Inc. | Use Of (1R,5S)-(+)-(Napthalen-2-yl)-3-Azabicyclo[3.1.0]Hexane In The Treatment Of Conditions Affected By Monoamine Neurotransmitters |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1351754A (en) * | 1970-07-02 | 1974-05-01 | Allen & Hanburys Ltd | Indenopyrrole derivatives |
-
1977
- 1977-08-16 GR GR54169A patent/GR72713B/el unknown
- 1977-08-26 AR AR268968A patent/AR220684A1/es active
- 1977-09-01 AU AU28441/77A patent/AU519620B2/en not_active Ceased
- 1977-09-02 NL NLAANVRAGE7709691,A patent/NL189041C/xx not_active IP Right Cessation
- 1977-09-08 DE DE19772740562 patent/DE2740562A1/de active Granted
- 1977-09-13 YU YU2174/77A patent/YU39499B/xx unknown
- 1977-09-13 CH CH1118977A patent/CH637929A5/de not_active IP Right Cessation
- 1977-09-14 PL PL1977200831A patent/PL115869B1/pl unknown
- 1977-09-14 DK DK407577A patent/DK146245C/da not_active IP Right Cessation
- 1977-09-14 HU HU77AE508A patent/HU177531B/hu unknown
- 1977-09-14 BE BE180894A patent/BE858683A/xx not_active IP Right Cessation
- 1977-09-14 FR FR7727755A patent/FR2375212A1/fr active Granted
- 1977-09-14 AT AT0661577A patent/AT367036B/de not_active IP Right Cessation
- 1977-09-15 SE SE7710367A patent/SE435384B/xx not_active IP Right Cessation
- 1977-09-15 DD DD77201039A patent/DD133943A5/xx unknown
- 1977-09-16 JP JP11064777A patent/JPS5337656A/ja active Granted
-
1978
- 1978-09-19 AR AR273764A patent/AR227507A1/es active
-
1980
- 1980-05-30 AT AT0288280A patent/AT367037B/de not_active IP Right Cessation
- 1980-10-16 DK DK438580A patent/DK438580A/da not_active Application Discontinuation
- 1980-10-16 DK DK438480A patent/DK438480A/da not_active Application Discontinuation
-
1982
- 1982-04-05 CH CH209382A patent/CH637931A5/de not_active IP Right Cessation
- 1982-06-03 SE SE8203437A patent/SE452610B/sv not_active IP Right Cessation
- 1982-08-23 YU YU1885/82A patent/YU43523B/xx unknown
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| PL | Patent ceased |