FI57253C - Foerfarande foer framstaellning av nya farmakodynamiskt aktiva basiskt substituerade indanderivat - Google Patents
Foerfarande foer framstaellning av nya farmakodynamiskt aktiva basiskt substituerade indanderivat Download PDFInfo
- Publication number
- FI57253C FI57253C FI817/73A FI81773A FI57253C FI 57253 C FI57253 C FI 57253C FI 817/73 A FI817/73 A FI 817/73A FI 81773 A FI81773 A FI 81773A FI 57253 C FI57253 C FI 57253C
- Authority
- FI
- Finland
- Prior art keywords
- group
- cyclopentane
- formula
- methyl
- spiro
- Prior art date
Links
- 230000003285 pharmacodynamic effect Effects 0.000 title description 2
- 238000006467 substitution reaction Methods 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 31
- -1 methyl-substituted ethylene Chemical group 0.000 claims description 29
- 150000001412 amines Chemical class 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 11
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical class C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 10
- 150000003512 tertiary amines Chemical class 0.000 claims description 10
- 150000002468 indanes Chemical class 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 8
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 150000003335 secondary amines Chemical class 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 2
- YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical compound C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 0.000 claims description 2
- 229910001507 metal halide Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 1
- 239000006188 syrup Substances 0.000 claims 1
- 235000020357 syrup Nutrition 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- 239000000243 solution Substances 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- 239000003921 oil Substances 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000155 melt Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 125000003003 spiro group Chemical group 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000003840 hydrochlorides Chemical class 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical class C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- VRUIUDIBGSGNPG-UHFFFAOYSA-N spiro[1,2-dihydroindene-3,1'-cyclopentane] Chemical compound C1CCCC21C1=CC=CC=C1CC2 VRUIUDIBGSGNPG-UHFFFAOYSA-N 0.000 description 5
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 4
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 4
- 229960003147 reserpine Drugs 0.000 description 4
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- DHGPGMQFHONYSE-UHFFFAOYSA-N spiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C12=CC=CC=C2C(=O)CC21CCCC2 DHGPGMQFHONYSE-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- YRXAUOCYBRMCIH-UHFFFAOYSA-N 1-chlorospiro[1,2-dihydroindene-3,1'-cyclopentane] Chemical compound C12=CC=CC=C2C(Cl)CC21CCCC2 YRXAUOCYBRMCIH-UHFFFAOYSA-N 0.000 description 2
- RVQWYPIHHAEQTH-UHFFFAOYSA-N 2-spiro[2h-indene-3,1'-cyclopentane]-1-ylideneacetic acid Chemical compound C12=CC=CC=C2C(=CC(=O)O)CC21CCCC2 RVQWYPIHHAEQTH-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
- YUPAAKDKZFBNNN-UHFFFAOYSA-N 6-aminospiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C=1C(N)=CC=C2C=1C(=O)CC21CCCC1 YUPAAKDKZFBNNN-UHFFFAOYSA-N 0.000 description 2
- DEBFCIDOEVIOAM-UHFFFAOYSA-N 6-chlorospiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C=1C(Cl)=CC=C2C=1C(=O)CC21CCCC1 DEBFCIDOEVIOAM-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000000891 anti-reserpine Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 150000002469 indenes Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- LFIQJCVEUQWRSS-UHFFFAOYSA-N spiro[2,3-dihydroindene-1,1'-cyclopentane]-5-amine Chemical compound NC=1C=C2CCC3(CCCC3)C2=CC1 LFIQJCVEUQWRSS-UHFFFAOYSA-N 0.000 description 2
- JUPFIGGSENJBQL-UHFFFAOYSA-N spiro[cyclopentane-1,1'-indene] Chemical compound C1CCCC21C1=CC=CC=C1C=C2 JUPFIGGSENJBQL-UHFFFAOYSA-N 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- KBRUFUBLFBZSQW-UHFFFAOYSA-N 2'-propylspiro[cyclopentane-1,1'-indene] Chemical compound C(CC)C=1C2(C3=CC=CC=C3C=1)CCCC2 KBRUFUBLFBZSQW-UHFFFAOYSA-N 0.000 description 1
- IGTKMZUYAWEOHI-UHFFFAOYSA-N 2-(3,3-dimethyl-2h-inden-1-ylidene)-n,n-dimethylacetamide Chemical compound C1=CC=C2C(=CC(=O)N(C)C)CC(C)(C)C2=C1 IGTKMZUYAWEOHI-UHFFFAOYSA-N 0.000 description 1
- OSTBRPMRPCVZAN-UHFFFAOYSA-N 2-(3,3-dimethyl-2h-inden-1-ylidene)-n-methylacetamide Chemical compound C1=CC=C2C(=CC(=O)NC)CC(C)(C)C2=C1 OSTBRPMRPCVZAN-UHFFFAOYSA-N 0.000 description 1
- ROMZFCVRIQBQSS-UHFFFAOYSA-N 2-(3,3-dimethyl-2h-inden-1-ylidene)acetamide Chemical compound C1=CC=C2C(C)(C)CC(=CC(N)=O)C2=C1 ROMZFCVRIQBQSS-UHFFFAOYSA-N 0.000 description 1
- PDPVDRFZQKRZIX-UHFFFAOYSA-N 2-(3,3-dimethyl-2h-inden-1-ylidene)acetic acid Chemical compound C1=CC=C2C(C)(C)CC(=CC(O)=O)C2=C1 PDPVDRFZQKRZIX-UHFFFAOYSA-N 0.000 description 1
- LCLUOTYRLQGHCJ-UHFFFAOYSA-N 2-(6-chlorospiro[2h-indene-3,1'-cyclopentane]-1-ylidene)acetic acid Chemical compound C12=CC=C(Cl)C=C2C(=CC(=O)O)CC21CCCC2 LCLUOTYRLQGHCJ-UHFFFAOYSA-N 0.000 description 1
- NQHXCFMNKMJQMF-UHFFFAOYSA-N 2-spiro[2h-indene-3,1'-cyclopentane]-1-ylideneacetonitrile Chemical compound C12=CC=CC=C2C(=CC#N)CC21CCCC2 NQHXCFMNKMJQMF-UHFFFAOYSA-N 0.000 description 1
- MOLCDZQBOUICDO-UHFFFAOYSA-N 2-spiro[2h-indene-3,1'-cyclopentane]-1-ylideneethanamine Chemical compound C12=CC=CC=C2C(=CCN)CC21CCCC2 MOLCDZQBOUICDO-UHFFFAOYSA-N 0.000 description 1
- QWZAOSKLFKAEOK-UHFFFAOYSA-N 3,3-dimethyl-2h-inden-1-one Chemical compound C1=CC=C2C(C)(C)CC(=O)C2=C1 QWZAOSKLFKAEOK-UHFFFAOYSA-N 0.000 description 1
- YQIALXGEJXSZIT-UHFFFAOYSA-N 6-fluorospiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C=1C(F)=CC=C2C=1C(=O)CC21CCCC1 YQIALXGEJXSZIT-UHFFFAOYSA-N 0.000 description 1
- JGHZRQIFVXHXPF-UHFFFAOYSA-N 6-hydroxyspiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C=1C(O)=CC=C2C=1C(=O)CC21CCCC1 JGHZRQIFVXHXPF-UHFFFAOYSA-N 0.000 description 1
- IZECYGQYHHGYQM-UHFFFAOYSA-N 6-methoxyspiro[2h-indene-3,1'-cyclopentane]-1-one Chemical compound C=1C(OC)=CC=C2C=1C(=O)CC21CCCC1 IZECYGQYHHGYQM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- AQKGPRGFKXWCTO-UHFFFAOYSA-N B(F)(F)F.[Na] Chemical compound B(F)(F)F.[Na] AQKGPRGFKXWCTO-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZPEOJFBVTXFXHD-UHFFFAOYSA-N C12(C=CC3=CC=CC=C13)CC(CC2)CC#N Chemical compound C12(C=CC3=CC=CC=C13)CC(CC2)CC#N ZPEOJFBVTXFXHD-UHFFFAOYSA-N 0.000 description 1
- LUASNHFCFISBRG-UHFFFAOYSA-N C12(CC(C3=CC=CC=C13)=CC(C)=O)CCCC2 Chemical compound C12(CC(C3=CC=CC=C13)=CC(C)=O)CCCC2 LUASNHFCFISBRG-UHFFFAOYSA-N 0.000 description 1
- VDAANAQBJLGJKK-UHFFFAOYSA-N C12(CCC3=CC=CC=C13)CC(CC2)=O Chemical compound C12(CCC3=CC=CC=C13)CC(CC2)=O VDAANAQBJLGJKK-UHFFFAOYSA-N 0.000 description 1
- UHYVXGJEVONKDO-UHFFFAOYSA-N CCCC1=C(C2=CC=CC=C2C13CCCCC3)N(C)C(=O)OCC Chemical compound CCCC1=C(C2=CC=CC=C2C13CCCCC3)N(C)C(=O)OCC UHYVXGJEVONKDO-UHFFFAOYSA-N 0.000 description 1
- XXNJWBZTBRVFGL-UHFFFAOYSA-N CN(C)C1=C(C2(C3=CC=CC=C13)CCCC2)C(C)C Chemical compound CN(C)C1=C(C2(C3=CC=CC=C13)CCCC2)C(C)C XXNJWBZTBRVFGL-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- CIYBMCJCRGFZCZ-UHFFFAOYSA-N N-methyl-2-spiro[cyclopentane-3,1'-indene]-1-ylethanamine Chemical compound CNCCC1CC2(C=CC3=CC=CC=C23)CC1 CIYBMCJCRGFZCZ-UHFFFAOYSA-N 0.000 description 1
- ZCAJJEILVLICRQ-UHFFFAOYSA-N NC(C)C=1C2(C3=CC=CC=C3C1)CCCC2 Chemical compound NC(C)C=1C2(C3=CC=CC=C3C1)CCCC2 ZCAJJEILVLICRQ-UHFFFAOYSA-N 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-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
- LAXJKTJWPMFRPZ-UHFFFAOYSA-N S(=O)(=O)(OC)O.C(C)=C1C2(C3=CC=CC=C3C1)CCCC2 Chemical compound S(=O)(=O)(OC)O.C(C)=C1C2(C3=CC=CC=C3C1)CCCC2 LAXJKTJWPMFRPZ-UHFFFAOYSA-N 0.000 description 1
- JAKPUOCXQVATQL-UHFFFAOYSA-N S(=O)(=O)(OC)O.C(CC)C=1C2(C3=CC=CC=C3C1)CCCC2 Chemical compound S(=O)(=O)(OC)O.C(CC)C=1C2(C3=CC=CC=C3C1)CCCC2 JAKPUOCXQVATQL-UHFFFAOYSA-N 0.000 description 1
- DIGXGNHHEITEDX-UHFFFAOYSA-N S(=O)(=O)(OC)O.C12(C=CC3=CC=CC=C13)CCCC2 Chemical compound S(=O)(=O)(OC)O.C12(C=CC3=CC=CC=C13)CCCC2 DIGXGNHHEITEDX-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- AYVGBNGTBQLJBG-UHFFFAOYSA-N [3-(hydroxymethyl)cyclopentyl]methanol Chemical compound OCC1CCC(CO)C1 AYVGBNGTBQLJBG-UHFFFAOYSA-N 0.000 description 1
- QGZNMXOKPQPNMY-UHFFFAOYSA-N [Mg].[Cl] Chemical class [Mg].[Cl] QGZNMXOKPQPNMY-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001339 alkali metal compounds Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- QWKFMUXHBYXUCA-UHFFFAOYSA-N but-1-enyl hydrogen sulfate Chemical compound CCC=COS(O)(=O)=O QWKFMUXHBYXUCA-UHFFFAOYSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- KVIPHDKUOLVVQN-UHFFFAOYSA-N ethene;hydrate Chemical compound O.C=C KVIPHDKUOLVVQN-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- IYRWEQXVUNLMAY-UHFFFAOYSA-N fluoroketone group Chemical group FC(=O)F IYRWEQXVUNLMAY-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- NAUNRGYRPJIDLZ-UHFFFAOYSA-N n,n-dimethyl-2-spiro[2h-indene-3,1'-cyclohexane]-1-ylideneacetamide Chemical compound C12=CC=CC=C2C(=CC(=O)N(C)C)CC21CCCCC2 NAUNRGYRPJIDLZ-UHFFFAOYSA-N 0.000 description 1
- RWPDAVAQUANBSQ-UHFFFAOYSA-N n,n-dimethyl-2-spiro[2h-indene-3,1'-cyclopentane]-1-ylideneethanamine Chemical compound C12=CC=CC=C2C(=CCN(C)C)CC21CCCC2 RWPDAVAQUANBSQ-UHFFFAOYSA-N 0.000 description 1
- GMOJNAPUKQOWIL-UHFFFAOYSA-N n-methyl-2-spiro[2h-indene-3,1'-cyclopentane]-1-ylideneethanamine Chemical compound C12=CC=CC=C2C(=CCNC)CC21CCCC2 GMOJNAPUKQOWIL-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SAALQYKUFCIMHR-UHFFFAOYSA-N propan-2-ol;2-propan-2-yloxypropane Chemical compound CC(C)O.CC(C)OC(C)C SAALQYKUFCIMHR-UHFFFAOYSA-N 0.000 description 1
- AAZYNPCMLRQUHI-UHFFFAOYSA-N propan-2-one;2-propan-2-yloxypropane Chemical compound CC(C)=O.CC(C)OC(C)C AAZYNPCMLRQUHI-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- JRSDGJVHYMRHMF-UHFFFAOYSA-N spiro[1,2-dihydroindene-3,1'-cyclohexane] Chemical compound C12=CC=CC=C2CCC21CCCCC2 JRSDGJVHYMRHMF-UHFFFAOYSA-N 0.000 description 1
- YJSHNXNGZFWVGO-UHFFFAOYSA-N spiro[2h-indene-3,1'-cyclohexane]-1-one Chemical compound C12=CC=CC=C2C(=O)CC21CCCCC2 YJSHNXNGZFWVGO-UHFFFAOYSA-N 0.000 description 1
- PEZQQSSHQCXWBQ-UHFFFAOYSA-N spiro[cyclohexane-1,1'-indene] Chemical compound C1CCCCC21C1=CC=CC=C1C=C2 PEZQQSSHQCXWBQ-UHFFFAOYSA-N 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
- C07C49/665—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings a keto group being part of a condensed ring system
- C07C49/675—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings a keto group being part of a condensed ring system having three rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/687—Unsaturated compounds containing a keto groups being part of a ring containing halogen
- C07C49/697—Unsaturated compounds containing a keto groups being part of a ring containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/62—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings and other rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE390572 | 1972-03-24 | ||
| SE7203905A SE371190B (en, 2012) | 1972-03-24 | 1972-03-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FI57253B FI57253B (fi) | 1980-03-31 |
| FI57253C true FI57253C (fi) | 1980-07-10 |
Family
ID=20263107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI817/73A FI57253C (fi) | 1972-03-24 | 1973-03-16 | Foerfarande foer framstaellning av nya farmakodynamiskt aktiva basiskt substituerade indanderivat |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4172093A (en, 2012) |
| JP (1) | JPS599540B2 (en, 2012) |
| AT (1) | AT329045B (en, 2012) |
| CA (1) | CA1032165A (en, 2012) |
| CH (4) | CH621110A5 (en, 2012) |
| DE (1) | DE2314636C2 (en, 2012) |
| DK (1) | DK138598B (en, 2012) |
| FI (1) | FI57253C (en, 2012) |
| FR (1) | FR2177929B1 (en, 2012) |
| GB (1) | GB1421208A (en, 2012) |
| NO (1) | NO138628C (en, 2012) |
| SE (1) | SE371190B (en, 2012) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA784349B (en) * | 1977-08-05 | 1979-07-25 | Kabi Ab | Geminally disubstituted indene derivatives |
| CH641147A5 (de) * | 1979-01-17 | 1984-02-15 | Sandoz Ag | 3-amino-2-hydroxypropoxyaryl-derivat, seine herstellung und dieses enthaltende heilmittel. |
| CH647235A5 (de) * | 1980-02-13 | 1985-01-15 | Sandoz Ag | 4-(2,2-dialkylindan-1-yliden)piperidin derivate, ihre herstellung und verwendung. |
| IL103106A (en) * | 1991-09-25 | 1998-06-15 | Sanofi Elf | Ethers of thienocyclopentanone oximes, their preparation and pharmaceutical compositions containing them |
| GB9309621D0 (en) * | 1993-05-11 | 1993-06-23 | Wellcome Found | Amide derivatives and their therapeutic use |
| US5914349A (en) * | 1994-01-10 | 1999-06-22 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| MY113062A (en) * | 1994-05-10 | 2001-11-30 | The Wellcome Foundation Ltd | Amide derivatives and their therapeutic use |
| JP4222632B2 (ja) | 1996-12-18 | 2009-02-12 | テバ・ファーマシューティカル・インダストリーズ・リミテッド | アミノインダン誘導体 |
| US6124284A (en) * | 1998-07-16 | 2000-09-26 | Glaxo Wellcome Inc. | Bicyclic amide derivatives and their use as muscle relaxants |
| US6737547B1 (en) | 1998-12-31 | 2004-05-18 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using N-acyl-1H-aminoindenes |
| US20040010038A1 (en) * | 2002-02-27 | 2004-01-15 | Eran Blaugrund | Propargylamino indan derivatives and propargylamino tetralin derivatives as brain-selective MAO inhibitors |
| GB0328906D0 (en) | 2003-12-12 | 2004-01-14 | Syngenta Participations Ag | Chemical compounds |
| AU2006326642B2 (en) * | 2005-12-09 | 2012-05-03 | Technion Research And Development Foundation Ltd. | Use of low-dose ladostigil for neuroprotection |
| US20070135518A1 (en) * | 2005-12-09 | 2007-06-14 | Marta Weinstock-Rosin | Use of low-dose ladostigil for neuroprotection |
| TW200744576A (en) * | 2006-02-24 | 2007-12-16 | Teva Pharma | Propargylated aminoindans, processes for preparation, and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1007323B (de) * | 1956-04-13 | 1957-05-02 | Schering Ag | Verfahren zur Herstellung von 1-Aminoindanen mit coronargefaesserweiternder Wirkung |
| US3308157A (en) * | 1964-08-07 | 1967-03-07 | Colgate Palmolive Co | N-(benzocyclobutene-1-loweralkyl)-carboxylic acid amides |
| US3360435A (en) * | 1964-09-15 | 1967-12-26 | Mead Johnson & Co | Treatment of depressed states |
| US3553093A (en) * | 1965-03-19 | 1971-01-05 | Xerox Corp | Color photoelectrophoretic imaging process |
| GB1139135A (en) * | 1965-10-01 | 1969-01-08 | Kefalas As | Aminoalkyl-substituted indanes and pharmaceutical compositions containing them |
| CH554829A (de) * | 1968-04-23 | 1974-10-15 | Ciba Geigy Ag | Verfahren zur herstellung von neuen aminoalkyl-(bzw. 1aminoalkyliden-) benzcycloalkan-2-spirocycloaliphatischen verbindungen. |
| US3657440A (en) * | 1968-04-23 | 1972-04-18 | Ciba Geigy Corp | Aminoalkyl-spirocycloalkanes as analgetic agents |
-
1972
- 1972-03-24 SE SE7203905A patent/SE371190B/xx unknown
-
1973
- 1973-03-16 FI FI817/73A patent/FI57253C/fi active
- 1973-03-20 US US05/343,129 patent/US4172093A/en not_active Expired - Lifetime
- 1973-03-20 CA CA166,508A patent/CA1032165A/en not_active Expired
- 1973-03-22 DK DK156173AA patent/DK138598B/da not_active IP Right Cessation
- 1973-03-22 AT AT255373A patent/AT329045B/de not_active IP Right Cessation
- 1973-03-23 JP JP48032772A patent/JPS599540B2/ja not_active Expired
- 1973-03-23 GB GB1422473A patent/GB1421208A/en not_active Expired
- 1973-03-23 NO NO1209/73A patent/NO138628C/no unknown
- 1973-03-23 CH CH428173A patent/CH621110A5/de not_active IP Right Cessation
- 1973-03-23 DE DE2314636A patent/DE2314636C2/de not_active Expired
- 1973-03-23 FR FR7310580A patent/FR2177929B1/fr not_active Expired
-
1979
- 1979-01-12 CH CH32579A patent/CH626044A5/de not_active IP Right Cessation
- 1979-01-12 CH CH32679A patent/CH622769A5/de not_active IP Right Cessation
- 1979-01-12 CH CH32779A patent/CH626045A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI57253B (fi) | 1980-03-31 |
| JPS599540B2 (ja) | 1984-03-03 |
| SE371190B (en, 2012) | 1974-11-11 |
| CH626045A5 (en, 2012) | 1981-10-30 |
| FR2177929A1 (en, 2012) | 1973-11-09 |
| DK138598C (en, 2012) | 1979-03-26 |
| CH626044A5 (en, 2012) | 1981-10-30 |
| FR2177929B1 (en, 2012) | 1976-10-22 |
| CA1032165A (en) | 1978-05-30 |
| CH622769A5 (en, 2012) | 1981-04-30 |
| NO138628C (no) | 1978-10-11 |
| DE2314636A1 (de) | 1973-10-04 |
| AT329045B (de) | 1976-04-26 |
| NO138628B (no) | 1978-07-03 |
| US4172093A (en) | 1979-10-23 |
| CH621110A5 (en, 2012) | 1981-01-15 |
| GB1421208A (en) | 1976-01-14 |
| AU5365173A (en) | 1974-09-26 |
| DK138598B (da) | 1978-10-02 |
| DE2314636C2 (de) | 1986-09-11 |
| JPS495957A (en, 2012) | 1974-01-19 |
| ATA255373A (de) | 1975-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI57253C (fi) | Foerfarande foer framstaellning av nya farmakodynamiskt aktiva basiskt substituerade indanderivat | |
| US4080449A (en) | 1,2,4,5-Tetrahydro-3H-2-benzazepin-3-ones | |
| US3420851A (en) | Novel dibenzoxepines | |
| Johnson et al. | Ring closure of the 2-benzoylaminocyclohexanols. The mechanism of oxazoline formation | |
| US4213985A (en) | Novel 5,11-dihydro-6H-pyrido-[2,3-b][1,4]-benzodiazepine-6-ones | |
| US4272533A (en) | N-Phenylindoline derivatives, and pharmaceutical compositions containing them | |
| US3068222A (en) | Trifluoromethyl substituted dibenzxze- | |
| CS272238B2 (en) | Method of 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid production | |
| Sarges et al. | Synthesis of aryl-substituted 1, 3-and 1, 4-diazocine derivatives | |
| US4220771A (en) | 2,3-Polymethylene-4-oxo-4H-pyrido[1,2-a]pyrimidines | |
| Cromwell et al. | Ethylenimine Ketones. XII. Stereoisomerism of 1-Cyclohexyl-2-(o-nitrophenyl)-3-benzoylethylenimine. Quinoline Syntheses | |
| US3358027A (en) | Dibenzazulenes | |
| US3149159A (en) | Substituted 7-aminoalkylbicyclo-[4. 2. 0] octa-1, 3, 5-trienes | |
| US3131190A (en) | 9-aminoalkyl and 9-aminoalkylidene derivatives of acridan | |
| NZ202981A (en) | A process for the preparation of pyrazino(2,1-a)isoquinoline derivatives | |
| US4157399A (en) | Benzo(B)thiophenes | |
| CA1056834A (en) | 3-(4-bromophenyl)-n-methyl-3-(3-pyridyl)-allylamine | |
| US3215739A (en) | Method of producing dibenzo (a, d) cyclohepta (1, 4) dienes | |
| EP0030749A1 (en) | Carboximidamide derivatives, a process for preparing them and pharmaceutical preparations containing same | |
| Cooper | Stereospecific synthesis of cis-and trans-2-(3, 4, 5-trimethoxyphenyl)-cyclopropylamines | |
| US3293251A (en) | Rearrangement process for j,b-diaza- bicyclo-(j,z,i)-octane derivatives | |
| US4927819A (en) | Cyclo-octane neuroprotective agents | |
| Rice et al. | Spirans XX. Synthesis of 8, 8‐dialkylazaspiro [4.5] decanes and 9, 9‐dialkylazaspiro [5.5] undecanes | |
| US3281469A (en) | Process for preparing 5-hydroxy-5-(3-aminoalkynyl) dibenzo [a, d] cyclohepta [1, 4] denes | |
| US4003930A (en) | 2,3-Trans-5-[3-(amino)-2-hydroxy-propoxy]-1,2,3,4-tetrahydro-3-(or 2)-amino-2-(or 3)-hydroxy-naphthalenes and salts thereof |