NO313234B1 - Fremgangsmåte for fremstilling av derivater av 4a,5,9,10,11,12,-heksahydro-6H-benzofuro[3a,3,2-ef][2]-benzazepiner og nye forbindelser - Google Patents
Fremgangsmåte for fremstilling av derivater av 4a,5,9,10,11,12,-heksahydro-6H-benzofuro[3a,3,2-ef][2]-benzazepiner og nye forbindelser Download PDFInfo
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- NO313234B1 NO313234B1 NO19971645A NO971645A NO313234B1 NO 313234 B1 NO313234 B1 NO 313234B1 NO 19971645 A NO19971645 A NO 19971645A NO 971645 A NO971645 A NO 971645A NO 313234 B1 NO313234 B1 NO 313234B1
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- Norway
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- group
- general formula
- compound
- hydrogen
- aralkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 140
- 238000000034 method Methods 0.000 title claims abstract description 81
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- UGMHRAPTMGMZRY-UHFFFAOYSA-N 11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-2,4,6(17),15-tetraene Chemical class C1CCC2C=3C4(C=CN=CC=31)C(O2)CCC=C4 UGMHRAPTMGMZRY-UHFFFAOYSA-N 0.000 title 1
- WGJYTAVHUDKGNK-UHFFFAOYSA-N O1C(C2=3)=CC=CC=3CNCCC22C1CCC=C2 Chemical compound O1C(C2=3)=CC=CC=3CNCCC22C1CCC=C2 WGJYTAVHUDKGNK-UHFFFAOYSA-N 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 127
- 229910052739 hydrogen Inorganic materials 0.000 claims description 113
- 239000002904 solvent Substances 0.000 claims description 67
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 54
- 150000002431 hydrogen Chemical class 0.000 claims description 48
- 229910052794 bromium Inorganic materials 0.000 claims description 45
- 238000010992 reflux Methods 0.000 claims description 45
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 43
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 43
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 42
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 39
- 229910001868 water Inorganic materials 0.000 claims description 39
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Substances OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 33
- 229910052731 fluorine Inorganic materials 0.000 claims description 33
- 125000003342 alkenyl group Chemical group 0.000 claims description 32
- 239000011737 fluorine Substances 0.000 claims description 32
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 31
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 31
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 30
- 229960003980 galantamine Drugs 0.000 claims description 28
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 27
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 27
- 150000002576 ketones Chemical class 0.000 claims description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 26
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 24
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 23
- 239000000047 product Substances 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 229910010084 LiAlH4 Inorganic materials 0.000 claims description 19
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 17
- -1 formyl alkylcarbonyl Chemical group 0.000 claims description 16
- 235000019253 formic acid Nutrition 0.000 claims description 15
- 239000003638 chemical reducing agent Substances 0.000 claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 13
- 238000001816 cooling Methods 0.000 claims description 13
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 239000012279 sodium borohydride Substances 0.000 claims description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 11
- 239000008096 xylene Substances 0.000 claims description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000001769 aryl amino group Chemical group 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001302 tertiary amino group Chemical group 0.000 claims description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 8
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 8
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 8
- 238000007243 oxidative cyclization reaction Methods 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 150000001555 benzenes Chemical class 0.000 claims description 7
- 230000031709 bromination Effects 0.000 claims description 7
- 238000005893 bromination reaction Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 229940095064 tartrate Drugs 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 6
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical compound [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 claims description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- 150000001449 anionic compounds Chemical class 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 229910001412 inorganic anion Inorganic materials 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 239000011591 potassium Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 239000011975 tartaric acid Substances 0.000 claims description 5
- 229960001367 tartaric acid Drugs 0.000 claims 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 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 150000008038 benzoazepines Chemical class 0.000 claims description 4
- 239000001110 calcium chloride Substances 0.000 claims description 4
- 235000011148 calcium chloride Nutrition 0.000 claims description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 4
- 239000007859 condensation product Substances 0.000 claims description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011701 zinc Substances 0.000 claims description 4
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 claims description 3
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 150000002009 diols Chemical class 0.000 claims description 3
- 150000002891 organic anions Chemical class 0.000 claims description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 229960004106 citric acid Drugs 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
- 229960001270 d- tartaric acid Drugs 0.000 claims description 2
- 150000004662 dithiols Chemical class 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 14
- 150000001336 alkenes Chemical class 0.000 claims 7
- 150000001345 alkine derivatives Chemical class 0.000 claims 7
- 150000002825 nitriles Chemical class 0.000 claims 7
- 150000001450 anions Chemical class 0.000 claims 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 125000002346 iodo group Chemical group I* 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 claims 2
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 claims 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 claims 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- 238000006482 condensation reaction Methods 0.000 claims 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims 1
- 125000004967 formylalkyl group Chemical group 0.000 claims 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims 1
- JEHCHYAKAXDFKV-UHFFFAOYSA-J lead tetraacetate Chemical compound CC(=O)O[Pb](OC(C)=O)(OC(C)=O)OC(C)=O JEHCHYAKAXDFKV-UHFFFAOYSA-J 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 239000012286 potassium permanganate Substances 0.000 claims 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 163
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- 239000000243 solution Substances 0.000 description 53
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 47
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
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- 238000002844 melting Methods 0.000 description 20
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
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- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 12
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- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT198094A AT401058B (de) | 1994-10-21 | 1994-10-21 | Verfahren zum herstellen von derivaten des 4a,5, 9,10,11,12,-hexahydro-6h-benzofuro(3a,-3,2-ef) (2)benzazepins |
| US48710295A | 1995-06-07 | 1995-06-07 | |
| PCT/AT1995/000208 WO1996012692A1 (de) | 1994-10-21 | 1995-10-23 | VERFAHREN ZUM HERSTELLEN VON DERIVATEN DES 4a,5,9,10,11,12,-HEXAHYDRO-6H-BENZOFURO[3a,3,2-ef][2]BENZAZEPINS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO971645D0 NO971645D0 (no) | 1997-04-10 |
| NO971645L NO971645L (no) | 1997-05-07 |
| NO313234B1 true NO313234B1 (no) | 2002-09-02 |
Family
ID=25597335
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19971645A NO313234B1 (no) | 1994-10-21 | 1997-04-10 | Fremgangsmåte for fremstilling av derivater av 4a,5,9,10,11,12,-heksahydro-6H-benzofuro[3a,3,2-ef][2]-benzazepiner og nye forbindelser |
| NO971796A NO971796L (no) | 1994-10-21 | 1997-04-18 | Fremgangsmåte for fremstilling av derivater av 4a,5,9,10,11,12,-heksahydro-6H-benzofuro(3a,3,2-ef)-(2)benzazepin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO971796A NO971796L (no) | 1994-10-21 | 1997-04-18 | Fremgangsmåte for fremstilling av derivater av 4a,5,9,10,11,12,-heksahydro-6H-benzofuro(3a,3,2-ef)-(2)benzazepin |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6043359A (pt) |
| EP (1) | EP0787115B1 (pt) |
| JP (1) | JP4187786B2 (pt) |
| KR (1) | KR100352212B1 (pt) |
| CN (1) | CN1069624C (pt) |
| AT (1) | ATE188460T1 (pt) |
| AU (1) | AU695352B2 (pt) |
| BG (1) | BG62133B1 (pt) |
| BR (1) | BR9509406A (pt) |
| CA (1) | CA2203183C (pt) |
| CZ (1) | CZ295528B6 (pt) |
| DE (1) | DE59507585D1 (pt) |
| DK (1) | DK0787115T3 (pt) |
| ES (1) | ES2106700T3 (pt) |
| FI (1) | FI114477B (pt) |
| GR (2) | GR980300015T1 (pt) |
| HU (1) | HU217207B (pt) |
| MX (1) | MX9702892A (pt) |
| NO (2) | NO313234B1 (pt) |
| NZ (1) | NZ294191A (pt) |
| PL (1) | PL184590B1 (pt) |
| PT (1) | PT787115E (pt) |
| RO (1) | RO118419B1 (pt) |
| RU (1) | RU2146258C1 (pt) |
| SI (1) | SI0787115T1 (pt) |
| SK (1) | SK283877B6 (pt) |
| WO (1) | WO1996012692A1 (pt) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9519267D0 (en) * | 1995-09-21 | 1995-11-22 | Chiroscience Ltd | Preparation of alkaloids |
| AT403803B (de) | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| GB9610887D0 (en) * | 1996-05-24 | 1996-07-31 | N H S Trust | Process |
| GB9707413D0 (en) * | 1997-04-11 | 1997-05-28 | Chiroscience Ltd | Process |
| CN1380883A (zh) * | 2000-03-31 | 2002-11-20 | 萨诺化学药物股份公司 | 雪花胺的新衍生物和类似物 |
| US6897228B2 (en) * | 2000-07-07 | 2005-05-24 | Medicure International Inc. | Pyridoxine and pyridoxal analogues: new uses |
| WO2002061457A2 (en) * | 2001-01-30 | 2002-08-08 | Decharms R Christopher | Methods for physiological monitoring, training, exercise and regulation |
| DE10129265A1 (de) * | 2001-06-18 | 2003-01-02 | Hf Arzneimittelforsch Gmbh | Wirkstoff-Kombination zur medikamentösen Sucht- oder Rauschmitteltherapie |
| DE10134038A1 (de) * | 2001-07-12 | 2003-02-06 | Hf Arzneimittelforsch Gmbh | Wirkstoff-Kombination zur medikamentösen Therapie der Nikotinabhängigkeit |
| AT414125B (de) * | 2003-09-29 | 2006-09-15 | Sanochemia Pharmazeutika Ag | Neue derivate des 4a,5,9,10,11,12-hexahydro- benzofuro(3a,3,2)(2) benzazepin, verfahren zu deren herstellung sowie deren verwendung zur herstellung von arzneimitteln |
| CA2506282A1 (en) * | 2003-09-29 | 2005-04-07 | Sanochemia Pharmazeutika Ag | Use of galanthamine and the derivatives thereof in the production of medicaments |
| US20050142193A1 (en) * | 2003-12-31 | 2005-06-30 | Lijuan Tang | Galantamine formulations |
| EP1763337A2 (en) * | 2003-12-31 | 2007-03-21 | Actavis Group HF | Immediate, controlled and sustained release formulations of galanthamine |
| WO2006013546A2 (en) * | 2004-07-28 | 2006-02-09 | Ranbaxy Laboratories Limited | Process for the preparation of pure galantamine |
| WO2006018703A2 (en) * | 2004-08-16 | 2006-02-23 | Ranbaxy Laboratories Limited | Processes for preparation of narwedine and its use in the synthesis of galantamine |
| AR054753A1 (es) * | 2005-05-03 | 2007-07-11 | Medichem Sa | Sintesis y preparaciones de narwedina galantamina y compuestos relacionados |
| AT504663B1 (de) | 2007-02-22 | 2008-07-15 | Sanochemia Pharmazeutika Ag | Verfahren zum herstellen von hochreinen 4a,5,9,10,11,12,-hexahydro-6h-benzofuro(3a,3,2- f)(2) benzazepinen sowie dessen derivaten |
| ES2432405T3 (es) * | 2007-04-12 | 2013-12-03 | Scinopharm Taiwan Ltd. | Procedimiento para preparar Galantamina |
| EP2009015B1 (en) | 2007-06-18 | 2012-01-11 | Aurobindo Pharma Limited | Process for the preparation of galantamine hydrobromide |
| AT507039A1 (de) * | 2008-06-26 | 2010-01-15 | Sanochemia Pharmazeutika Ag | Verfahren zum herstellen von hochreinen benzazepinderivaten |
| DE102008056086A1 (de) * | 2008-11-06 | 2010-05-12 | Gp Solar Gmbh | Additiv für alkalische Ätzlösungen, insbesondere für Texturätzlösungen sowie Verfahren zu dessen Herstellung |
| WO2013160728A1 (en) | 2012-04-26 | 2013-10-31 | Alma Mater Studiorum - Universita' Di Bologna | Dual targeting compounds for the treatment of alzheimer's disease |
| CN102924462B (zh) * | 2012-10-24 | 2015-01-14 | 华东师范大学 | 1,2,3,4,5,9-取代苯并吖庚因类化合物的合成方法 |
| CN103345954B (zh) * | 2013-06-20 | 2016-06-08 | 哈尔滨工业大学 | 一种高锰酸盐与活性炭联用去除放射性碘污染的水处理方法 |
| CN109336897A (zh) * | 2018-12-06 | 2019-02-15 | 河南中帅医药科技股份有限公司 | 一种氢溴酸加兰他敏工业化制备方法 |
| CN112521364B (zh) * | 2019-09-17 | 2023-09-05 | 鲁南制药集团股份有限公司 | 一种加兰他敏中间体化合物v |
| CN112521395B (zh) * | 2019-09-17 | 2023-09-05 | 鲁南制药集团股份有限公司 | 一种加兰他敏的制备方法 |
| CN110714208B (zh) * | 2019-10-30 | 2020-12-29 | 常州工学院 | 一种电催化制备6-(磺酰甲基)菲啶类化合物的方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG28325A1 (en) * | 1978-11-21 | 1980-04-15 | Vlakhov | Method of obtaining of enons navedine type and their derivatives |
| US4290862A (en) * | 1979-11-14 | 1981-09-22 | Edinen Centar P Chimia | Method for the preparation of narwedine-type enones |
| US4663318A (en) * | 1986-01-15 | 1987-05-05 | Bonnie Davis | Method of treating Alzheimer's disease |
| AU632458B2 (en) * | 1987-05-04 | 1993-01-07 | Bonnie Davis | Compounds for the treatment of alzheimer's disease |
| US5428159A (en) * | 1994-04-08 | 1995-06-27 | Ciba-Geigy Corporation | Method of manufacture of (-)-galanthamine in high yield and purity substantially free of epigalanthamine |
-
1995
- 1995-10-23 RU RU97107848A patent/RU2146258C1/ru active
- 1995-10-23 WO PCT/AT1995/000208 patent/WO1996012692A1/de active IP Right Grant
- 1995-10-23 CA CA002203183A patent/CA2203183C/en not_active Expired - Lifetime
- 1995-10-23 PT PT95944807T patent/PT787115E/pt unknown
- 1995-10-23 ES ES95944807T patent/ES2106700T3/es not_active Expired - Lifetime
- 1995-10-23 BR BR9509406A patent/BR9509406A/pt not_active Application Discontinuation
- 1995-10-23 PL PL95319754A patent/PL184590B1/pl unknown
- 1995-10-23 AT AT95944807T patent/ATE188460T1/de active
- 1995-10-23 EP EP95944807A patent/EP0787115B1/de not_active Expired - Lifetime
- 1995-10-23 SK SK483-97A patent/SK283877B6/sk not_active IP Right Cessation
- 1995-10-23 NZ NZ294191A patent/NZ294191A/xx not_active IP Right Cessation
- 1995-10-23 CN CN95196432A patent/CN1069624C/zh not_active Expired - Lifetime
- 1995-10-23 JP JP51352796A patent/JP4187786B2/ja not_active Expired - Fee Related
- 1995-10-23 AU AU36938/95A patent/AU695352B2/en not_active Expired
- 1995-10-23 HU HU9800766A patent/HU217207B/hu unknown
- 1995-10-23 DK DK95944807T patent/DK0787115T3/da active
- 1995-10-23 KR KR1019970702612A patent/KR100352212B1/ko not_active IP Right Cessation
- 1995-10-23 RO RO97-00721A patent/RO118419B1/ro unknown
- 1995-10-23 SI SI9530182T patent/SI0787115T1/xx unknown
- 1995-10-23 CZ CZ19971195A patent/CZ295528B6/cs not_active IP Right Cessation
- 1995-10-23 DE DE59507585T patent/DE59507585D1/de not_active Expired - Lifetime
-
1997
- 1997-04-10 NO NO19971645A patent/NO313234B1/no not_active IP Right Cessation
- 1997-04-16 BG BG101417A patent/BG62133B1/bg unknown
- 1997-04-16 FI FI971609A patent/FI114477B/fi not_active IP Right Cessation
- 1997-04-18 NO NO971796A patent/NO971796L/no unknown
- 1997-04-18 US US08/839,350 patent/US6043359A/en not_active Expired - Lifetime
- 1997-04-21 MX MX9702892A patent/MX9702892A/es unknown
-
1998
- 1998-03-31 GR GR980300015T patent/GR980300015T1/el unknown
-
2000
- 2000-03-15 GR GR20000400665T patent/GR3032965T3/el unknown
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| MK1K | Patent expired |