FI79530C - Foerfarande foer framstaellning av farmakologiskt vaerdefulla 5-aminosulfonylmetyl-indolderivat. - Google Patents
Foerfarande foer framstaellning av farmakologiskt vaerdefulla 5-aminosulfonylmetyl-indolderivat. Download PDFInfo
- Publication number
- FI79530C FI79530C FI832035A FI832035A FI79530C FI 79530 C FI79530 C FI 79530C FI 832035 A FI832035 A FI 832035A FI 832035 A FI832035 A FI 832035A FI 79530 C FI79530 C FI 79530C
- Authority
- FI
- Finland
- Prior art keywords
- group
- formula
- compound
- indole
- general formula
- Prior art date
Links
- XMBRLURMRGTDJK-UHFFFAOYSA-N 1h-indol-5-ylmethanesulfonamide Chemical class NS(=O)(=O)CC1=CC=C2NC=CC2=C1 XMBRLURMRGTDJK-UHFFFAOYSA-N 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 149
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 88
- 239000000203 mixture Substances 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 36
- 230000002829 reductive effect Effects 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 19
- MURZXKIEJFJMPP-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN)C2=C1 MURZXKIEJFJMPP-UHFFFAOYSA-N 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 11
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- 150000002475 indoles Chemical class 0.000 claims description 6
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 5
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- YDTVAJYBEHCVJY-UHFFFAOYSA-N n-methyl-1-[3-[2-(methylamino)ethyl]-1h-indol-5-yl]methanesulfonamide Chemical compound C1=C(CS(=O)(=O)NC)C=C2C(CCNC)=CNC2=C1 YDTVAJYBEHCVJY-UHFFFAOYSA-N 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- VUYWONZJZHPBIZ-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-prop-2-enylmethanesulfonamide Chemical compound C1=C(CS(=O)(=O)NCC=C)C=C2C(CCN)=CNC2=C1 VUYWONZJZHPBIZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- AMQNZONUQVIKGD-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n,n-dimethylmethanesulfonamide Chemical compound CN(C)S(=O)(=O)CC1=CC=C2NC=C(CCN)C2=C1 AMQNZONUQVIKGD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- NGPIHVRXGQAKTH-UHFFFAOYSA-N NCCC1(CNC2=CC=CC=C12)CS(=O)(=O)NC Chemical compound NCCC1(CNC2=CC=CC=C12)CS(=O)(=O)NC NGPIHVRXGQAKTH-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 222
- 239000000243 solution Substances 0.000 description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000047 product Substances 0.000 description 77
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 239000007787 solid Substances 0.000 description 53
- 238000004809 thin layer chromatography Methods 0.000 description 44
- 239000003921 oil Substances 0.000 description 37
- 239000000725 suspension Substances 0.000 description 36
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- -1 creatinine sulphate adducts Chemical class 0.000 description 29
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 24
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 24
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Natural products CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 23
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 229910052739 hydrogen Inorganic materials 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- 239000001257 hydrogen Substances 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 17
- 239000003054 catalyst Substances 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 12
- 239000006071 cream Substances 0.000 description 12
- 229940109239 creatinine Drugs 0.000 description 12
- 239000011976 maleic acid Substances 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 229910003445 palladium oxide Inorganic materials 0.000 description 12
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- LTLKJYMNUSSFAH-UHFFFAOYSA-N 4-chloro-1,1-dimethoxybutane Chemical compound COC(OC)CCCCl LTLKJYMNUSSFAH-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 208000019695 Migraine disease Diseases 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 206010027599 migraine Diseases 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 229920000388 Polyphosphate Polymers 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000001205 polyphosphate Substances 0.000 description 6
- 235000011176 polyphosphates Nutrition 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000010288 sodium nitrite Nutrition 0.000 description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 4
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- QTEJRFMIQYQJRM-UHFFFAOYSA-N [3-(2-aminoethyl)-1h-indol-5-yl]methanesulfonamide Chemical compound C1=C(CS(N)(=O)=O)C=C2C(CCN)=CNC2=C1 QTEJRFMIQYQJRM-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229940124530 sulfonamide Drugs 0.000 description 4
- 150000003456 sulfonamides Chemical class 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 241000400611 Eucalyptus deanei Species 0.000 description 3
- 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 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 239000003377 acid catalyst Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000013081 microcrystal Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000001119 stannous chloride Substances 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000001384 succinic acid Substances 0.000 description 3
- VYLIVAAMSLPRIS-UHFFFAOYSA-N (4-nitrophenyl)methanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 VYLIVAAMSLPRIS-UHFFFAOYSA-N 0.000 description 2
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 2
- CIWNHTXCBHTWRV-UHFFFAOYSA-N 1-(4-aminophenyl)-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C(N)C=C1 CIWNHTXCBHTWRV-UHFFFAOYSA-N 0.000 description 2
- XDHAKNGXIPRSSX-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-(2-phenylethyl)methanesulfonamide Chemical compound C1=C2C(CCN)=CNC2=CC=C1CS(=O)(=O)NCCC1=CC=CC=C1 XDHAKNGXIPRSSX-UHFFFAOYSA-N 0.000 description 2
- PFHJCUVTWFXKEH-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-phenylmethanesulfonamide Chemical compound C1=C2C(CCN)=CNC2=CC=C1CS(=O)(=O)NC1=CC=CC=C1 PFHJCUVTWFXKEH-UHFFFAOYSA-N 0.000 description 2
- JKDQZXJVYVRMEZ-UHFFFAOYSA-N 1-[3-(2-chloroethyl)-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCCl)C2=C1 JKDQZXJVYVRMEZ-UHFFFAOYSA-N 0.000 description 2
- SEOYZWFXZMRJHB-UHFFFAOYSA-N 1-[3-(3-aminopropyl)-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCCN)C2=C1 SEOYZWFXZMRJHB-UHFFFAOYSA-N 0.000 description 2
- NMOCOWABJRWQGY-UHFFFAOYSA-N 2-(4,4-diethoxybutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCC(OCC)OCC)C(=O)C2=C1 NMOCOWABJRWQGY-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- XJHNCGVHPLDMRK-UHFFFAOYSA-N 4,4-dimethoxybutanenitrile Chemical compound COC(OC)CCC#N XJHNCGVHPLDMRK-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- VZDYWEUILIUIDF-UHFFFAOYSA-J cerium(4+);disulfate Chemical compound [Ce+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VZDYWEUILIUIDF-UHFFFAOYSA-J 0.000 description 2
- 229910000355 cerium(IV) sulfate Inorganic materials 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 229960001186 methysergide Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002560 nitrile group Chemical group 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000007790 scraping Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 150000003890 succinate salts Chemical class 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- NTYOKQYEVIDMCY-UHFFFAOYSA-N (4-aminophenyl)methanesulfonamide Chemical compound NC1=CC=C(CS(N)(=O)=O)C=C1 NTYOKQYEVIDMCY-UHFFFAOYSA-N 0.000 description 1
- LNFXPAJMYSDIHK-UHFFFAOYSA-N (4-hydrazinylphenyl)methanesulfonamide Chemical compound NNC1=CC=C(CS(N)(=O)=O)C=C1 LNFXPAJMYSDIHK-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- RRCHHBZKAZOKCL-UHFFFAOYSA-N 1-(4-aminophenyl)-n-cyclohexylmethanesulfonamide Chemical compound C1=CC(N)=CC=C1CS(=O)(=O)NC1CCCCC1 RRCHHBZKAZOKCL-UHFFFAOYSA-N 0.000 description 1
- XEFYMIDBRZPQDL-UHFFFAOYSA-N 1-(4-aminophenyl)-n-phenylmethanesulfonamide Chemical compound C1=CC(N)=CC=C1CS(=O)(=O)NC1=CC=CC=C1 XEFYMIDBRZPQDL-UHFFFAOYSA-N 0.000 description 1
- DZODFXKLAFRYEC-UHFFFAOYSA-N 1-(4-hydrazinylphenyl)-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C(NN)C=C1 DZODFXKLAFRYEC-UHFFFAOYSA-N 0.000 description 1
- RSOICGQTJZZKAC-UHFFFAOYSA-N 1-(4-hydrazinylphenyl)-n-phenylmethanesulfonamide Chemical compound C1=CC(NN)=CC=C1CS(=O)(=O)NC1=CC=CC=C1 RSOICGQTJZZKAC-UHFFFAOYSA-N 0.000 description 1
- JHXXZRYWPHADOE-UHFFFAOYSA-N 1-(4-nitrophenyl)-n-phenylmethanesulfonamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1CS(=O)(=O)NC1=CC=CC=C1 JHXXZRYWPHADOE-UHFFFAOYSA-N 0.000 description 1
- DEBUYIPOYKBSHR-UHFFFAOYSA-N 1-(4-nitrophenyl)-n-propan-2-ylmethanesulfonamide Chemical compound CC(C)NS(=O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 DEBUYIPOYKBSHR-UHFFFAOYSA-N 0.000 description 1
- DTWQYCXSPPQEEP-BTJKTKAUSA-N 1-[3-(2-aminoethyl)-1H-indol-5-yl]-N-ethylmethanesulfonamide (Z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.CCNS(=O)(=O)CC1=CC=C2NC=C(CCN)C2=C1 DTWQYCXSPPQEEP-BTJKTKAUSA-N 0.000 description 1
- YSVQPMMNVLTTDF-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-benzylmethanesulfonamide Chemical compound C1=C2C(CCN)=CNC2=CC=C1CS(=O)(=O)NCC1=CC=CC=C1 YSVQPMMNVLTTDF-UHFFFAOYSA-N 0.000 description 1
- KRARMSKMLWBOMY-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-cyclohexylmethanesulfonamide Chemical compound C1=C2C(CCN)=CNC2=CC=C1CS(=O)(=O)NC1CCCCC1 KRARMSKMLWBOMY-UHFFFAOYSA-N 0.000 description 1
- AFBYMGMXBHJYHZ-UHFFFAOYSA-N 1-[3-(2-aminoethyl)-1h-indol-5-yl]-n-propan-2-ylmethanesulfonamide Chemical compound CC(C)NS(=O)(=O)CC1=CC=C2NC=C(CCN)C2=C1 AFBYMGMXBHJYHZ-UHFFFAOYSA-N 0.000 description 1
- HYBOCMIZDNGJEY-UHFFFAOYSA-N 1-[3-(cyanomethyl)-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CC#N)C2=C1 HYBOCMIZDNGJEY-UHFFFAOYSA-N 0.000 description 1
- HTPOOUOLROIBLP-UHFFFAOYSA-N 1-[3-[3-(1,3-dioxoisoindol-2-yl)propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCC1=CNC2=CC=C(CS(=O)(=O)NC)C=C21 HTPOOUOLROIBLP-UHFFFAOYSA-N 0.000 description 1
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 1
- BOURNSWDLZGGGR-UHFFFAOYSA-N 2-(5,5-dimethoxypentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCC(OC)OC)C(=O)C2=C1 BOURNSWDLZGGGR-UHFFFAOYSA-N 0.000 description 1
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 description 1
- MEVXSUZBFYZPHZ-UHFFFAOYSA-N 2-amino-3-methyl-4h-imidazol-5-one;sulfuric acid Chemical compound OS(O)(=O)=O.CN1CC(=O)N=C1N MEVXSUZBFYZPHZ-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- ROZCUVMFXOURIS-UHFFFAOYSA-N 2-phenylethanesulfonamide Chemical compound NS(=O)(=O)CCC1=CC=CC=C1 ROZCUVMFXOURIS-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- JRASUUTVFCLPPO-UHFFFAOYSA-N 3-(2-chloroethyl)-1h-indole Chemical compound C1=CC=C2C(CCCl)=CNC2=C1 JRASUUTVFCLPPO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- GDVDQWWINLDHSX-UHFFFAOYSA-N 5-bromo-1,1-dimethoxypentane Chemical compound COC(OC)CCCCBr GDVDQWWINLDHSX-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
- 229910015900 BF3 Inorganic materials 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- MIZHIBPAKMQLOP-UHFFFAOYSA-N CCN(C)S(=O)(=O)CC1=CC=C2NC=CC2=C1 Chemical compound CCN(C)S(=O)(=O)CC1=CC=C2NC=CC2=C1 MIZHIBPAKMQLOP-UHFFFAOYSA-N 0.000 description 1
- ZAKQVNDKUMYJIQ-UHFFFAOYSA-N CCN(CC)S(=O)(=O)CC1=CC=C(C=C1)NN Chemical compound CCN(CC)S(=O)(=O)CC1=CC=C(C=C1)NN ZAKQVNDKUMYJIQ-UHFFFAOYSA-N 0.000 description 1
- PXIPOSNXFSLONS-UHFFFAOYSA-N CNS(=O)(=O)C1=CC=C(C=C1)NN=CCCC#N Chemical compound CNS(=O)(=O)C1=CC=C(C=C1)NN=CCCC#N PXIPOSNXFSLONS-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
- 229930195212 Fischerindole Natural products 0.000 description 1
- 229910003650 H2SO6 Inorganic materials 0.000 description 1
- GWESVXSMPKAFAS-UHFFFAOYSA-N Isopropylcyclohexane Natural products CC(C)C1CCCCC1 GWESVXSMPKAFAS-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000000944 Soxhlet extraction Methods 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- IZEQRYXPOFFPCG-UHFFFAOYSA-N [3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methanesulfonamide Chemical compound C1=C(CS(N)(=O)=O)C=C2C(CCN(C)C)=CNC2=C1 IZEQRYXPOFFPCG-UHFFFAOYSA-N 0.000 description 1
- LJBOWIAGZOMTMF-UHFFFAOYSA-N [3-[2-(methylamino)ethyl]-1h-indol-5-yl]methanesulfonamide Chemical compound C1=C(CS(N)(=O)=O)C=C2C(CCNC)=CNC2=C1 LJBOWIAGZOMTMF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 230000010339 dilation Effects 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
- 150000002009 diols Chemical class 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- ANFZRGMDGDYNGA-UHFFFAOYSA-N ethyl acetate;propan-2-ol Chemical compound CC(C)O.CCOC(C)=O ANFZRGMDGDYNGA-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- XBECWGJPSXHFCS-UHFFFAOYSA-N imidazole-1-carbaldehyde Chemical compound O=CN1C=CN=C1 XBECWGJPSXHFCS-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- XCHBZJJWNKOQMT-UHFFFAOYSA-N n-[2-[5-(methylsulfamoylmethyl)-1h-indol-3-yl]ethyl]formamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCNC=O)C2=C1 XCHBZJJWNKOQMT-UHFFFAOYSA-N 0.000 description 1
- YQLUTOXBDXUACW-UHFFFAOYSA-N n-benzyl-1-(4-nitrophenyl)methanesulfonamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1CS(=O)(=O)NCC1=CC=CC=C1 YQLUTOXBDXUACW-UHFFFAOYSA-N 0.000 description 1
- XTQAJNMHFSQUMT-UHFFFAOYSA-N n-cyclohexyl-1-(4-hydrazinylphenyl)methanesulfonamide Chemical compound C1=CC(NN)=CC=C1CS(=O)(=O)NC1CCCCC1 XTQAJNMHFSQUMT-UHFFFAOYSA-N 0.000 description 1
- KMLJULHFRBTYGV-UHFFFAOYSA-N n-ethyl-1-(4-hydrazinylphenyl)methanesulfonamide Chemical compound CCNS(=O)(=O)CC1=CC=C(NN)C=C1 KMLJULHFRBTYGV-UHFFFAOYSA-N 0.000 description 1
- KZWPBAASZYQWIV-UHFFFAOYSA-N n-methyl-1-(4-nitrophenyl)methanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 KZWPBAASZYQWIV-UHFFFAOYSA-N 0.000 description 1
- WVJHETOWFTYSIE-UHFFFAOYSA-N n-methyl-1-[3-(2-nitroethyl)-1h-indol-5-yl]methanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CC[N+]([O-])=O)C2=C1 WVJHETOWFTYSIE-UHFFFAOYSA-N 0.000 description 1
- SMFUSAKSENKDOJ-UHFFFAOYSA-N n-methyl-n-[(1-methylbenzimidazol-2-yl)methyl]butan-1-amine Chemical compound C1=CC=C2N(C)C(CN(C)CCCC)=NC2=C1 SMFUSAKSENKDOJ-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WQMOWDRIXRBJBW-UHFFFAOYSA-N phenyl(piperidin-1-yl)diazene Chemical compound C1CCCCN1N=NC1=CC=CC=C1 WQMOWDRIXRBJBW-UHFFFAOYSA-N 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8216526 | 1982-06-07 | ||
| GB8216526 | 1982-06-07 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI832035A0 FI832035A0 (fi) | 1983-06-07 |
| FI832035L FI832035L (fi) | 1983-12-08 |
| FI79530B FI79530B (fi) | 1989-09-29 |
| FI79530C true FI79530C (fi) | 1990-01-10 |
Family
ID=10530876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI832035A FI79530C (fi) | 1982-06-07 | 1983-06-07 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla 5-aminosulfonylmetyl-indolderivat. |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US4816470A (en:Method) |
| JP (1) | JPS5942366A (en:Method) |
| KR (1) | KR900006681B1 (en:Method) |
| AT (1) | AT381933B (en:Method) |
| AU (1) | AU566149B2 (en:Method) |
| BE (1) | BE896986A (en:Method) |
| CA (1) | CA1199643A (en:Method) |
| CH (1) | CH657359A5 (en:Method) |
| CY (1) | CY1458A (en:Method) |
| CZ (1) | CZ280529B6 (en:Method) |
| DE (2) | DE19375045I2 (en:Method) |
| DK (1) | DK260183D0 (en:Method) |
| DO (1) | DOP1989476000A (en:Method) |
| ES (3) | ES523039A0 (en:Method) |
| FI (1) | FI79530C (en:Method) |
| FR (1) | FR2530625B1 (en:Method) |
| GB (1) | GB2124210B (en:Method) |
| GR (1) | GR79215B (en:Method) |
| HK (1) | HK14789A (en:Method) |
| IE (1) | IE55358B1 (en:Method) |
| IL (1) | IL68913A (en:Method) |
| IT (1) | IT1170387B (en:Method) |
| KE (1) | KE3833A (en:Method) |
| LU (1) | LU84852A1 (en:Method) |
| MX (1) | MX9202623A (en:Method) |
| MY (1) | MY8700179A (en:Method) |
| NL (1) | NL193694C (en:Method) |
| NZ (1) | NZ204482A (en:Method) |
| PH (1) | PH19908A (en:Method) |
| PT (1) | PT76830B (en:Method) |
| SE (1) | SE452459B (en:Method) |
| SK (1) | SK277877B6 (en:Method) |
| ZA (1) | ZA834110B (en:Method) |
Families Citing this family (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8332437D0 (en) * | 1983-12-06 | 1984-01-11 | Glaxo Group Ltd | Chemical compounds |
| GB8332434D0 (en) * | 1983-12-06 | 1984-01-11 | Glaxo Group Ltd | Production of chemical compounds |
| GB8332435D0 (en) * | 1983-12-06 | 1984-01-11 | Glaxo Group Ltd | Chemical compounds |
| GB8419575D0 (en) * | 1984-08-01 | 1984-09-05 | Glaxo Group Ltd | Chemical compounds |
| US5270333A (en) * | 1986-01-28 | 1993-12-14 | Glaxo Group Limited | Indole derivatives |
| GB8601959D0 (en) * | 1986-01-28 | 1986-03-05 | Glaxo Group Ltd | Indole derivatives |
| GB8615599D0 (en) * | 1986-06-26 | 1986-07-30 | Glaxo Group Ltd | Chemical compounds |
| ATE92057T1 (de) * | 1987-08-13 | 1993-08-15 | Glaxo Group Ltd | Indol-derivate. |
| GB8719167D0 (en) * | 1987-08-13 | 1987-09-23 | Glaxo Group Ltd | Chemical compounds |
| US5225431A (en) * | 1987-10-23 | 1993-07-06 | Burroughs Wellcome Co. | Therapeutic substituted indole compounds and compositions thereof |
| GB8903036D0 (en) * | 1989-02-10 | 1989-03-30 | Glaxo Group Ltd | Chemical compounds |
| HUT57185A (en) * | 1990-03-21 | 1991-11-28 | Merrell Dow Pharma | Process for producing 8-sulfamil-methylen-2-amino-tetraline derivatives and pharmaceutical compositions containing them |
| US5935925A (en) * | 1990-05-08 | 1999-08-10 | Synaptic Pharmaceutical Corporation | Methods of treating migraine and compounds useful for such methods |
| US5155218A (en) | 1990-05-08 | 1992-10-13 | Neurogenetic Corporation | Dna encoding human 5-ht1d receptors |
| SI21560B (sl) * | 1990-06-07 | 2005-04-30 | Astrazeneca Ab | 3,5-disubstituirani indolni derivati kot "5-HT1-podobni" receptorski agonisti |
| GB9013845D0 (en) * | 1990-06-21 | 1990-08-15 | Glaxo Group Ltd | Process |
| CA2043709C (en) * | 1990-06-29 | 2002-01-22 | David W. Smith | Antimigraine alkoxypyrimidine derivatives |
| US5077293A (en) * | 1990-06-29 | 1991-12-31 | Bristol-Myers Squibb Co. | 1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines |
| GB9022250D0 (en) * | 1990-10-12 | 1990-11-28 | Glaxo Group Ltd | Medicaments |
| GB9103770D0 (en) * | 1991-02-22 | 1991-04-10 | Glaxo Group Ltd | Chemical compounds |
| GB9104890D0 (en) * | 1991-03-08 | 1991-04-24 | Glaxo Group Ltd | Compositions |
| CA2084531A1 (en) * | 1991-12-19 | 1993-06-20 | David W. Smith | Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkyl piperazines |
| GB9209882D0 (en) * | 1992-05-07 | 1992-06-24 | Glaxo Lab Sa | Compositions |
| GB9211276D0 (en) * | 1992-05-28 | 1992-07-15 | Glaxo Lab Sa | Pharmaceutical compositions |
| GB9211277D0 (en) | 1992-05-28 | 1992-07-15 | Glaxo Group Inc | Pharmaceutical compositions |
| ES2055651B1 (es) * | 1992-07-20 | 1995-03-01 | Vita Invest Sa | Procedimiento para la obtencion de nuevas amidinas derivadas de 3-aminoetilindoles. |
| GB9216009D0 (en) * | 1992-07-28 | 1992-09-09 | Almirall Lab | New indol derivatives |
| ES2056025B1 (es) * | 1992-10-08 | 1995-05-01 | Almirall Lab | Nuevos derivados de indol. |
| RU2108326C1 (ru) * | 1993-02-26 | 1998-04-10 | Вита-Инвест С.А. | Способ получения 2-карбокси-3-[2-(диметиламино)этил]-n-метил-1h-индол-5-метансульфонамида или его сложных эфиров |
| US5382592A (en) * | 1993-09-16 | 1995-01-17 | Bristol-Myers Squibb Company | Antimigraine cyclobutenedione derivatives of tryptamines |
| US5468768A (en) * | 1994-01-06 | 1995-11-21 | Bristol-Myers Squibb Company | Antimigraine derivatives of indolylcycloalkanylamines |
| ES2079323B1 (es) * | 1994-06-21 | 1996-10-16 | Vita Invest Sa | Derivados de indol utiles para el tratamiento de la migraña, composicion y uso correspondientes. |
| FR2731224B1 (fr) * | 1995-03-02 | 1997-05-30 | Pf Medicament | Nouveaux derives bi-tryptaminiques sulfonamides, leur procede de preparation et leur utilisation a titre de medicaments |
| US5618816A (en) * | 1995-03-02 | 1997-04-08 | Bristol-Myers Squibb Company | Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridnyl and pyrimidinylpiperazines |
| US8022095B2 (en) | 1996-08-16 | 2011-09-20 | Pozen, Inc. | Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs |
| US6586458B1 (en) | 1996-08-16 | 2003-07-01 | Pozen Inc. | Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs |
| US5872145A (en) * | 1996-08-16 | 1999-02-16 | Pozen, Inc. | Formulation of 5-HT agonist and NSAID for treatment of migraine |
| US6416472B1 (en) | 1997-11-06 | 2002-07-09 | Edus Inc. | Method and device for measuring cognitive efficiency |
| US6066092A (en) * | 1997-11-06 | 2000-05-23 | Cady; Roger K. | Preemptive prophylaxis of migraine device and method |
| US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
| GB9926250D0 (en) * | 1999-11-06 | 2000-01-12 | Knoll Ag | Chemical process |
| WO2002015899A1 (en) * | 2000-08-23 | 2002-02-28 | Bristol-Myers Squibb Company | Combination therapy for the treatment of migraine |
| CN1536986B (zh) * | 2001-03-27 | 2012-07-04 | 沃纳奇尔科特(爱尔兰)有限公司 | 用于抗微生物剂给药的阴道内药物递送装置 |
| US8329734B2 (en) | 2009-07-27 | 2012-12-11 | Afgin Pharma Llc | Topical therapy for migraine |
| DE60228294D1 (en) * | 2001-06-05 | 2008-09-25 | Ronald Aung-Din | Topische migränetherapie |
| CN1649614A (zh) | 2002-02-22 | 2005-08-03 | 新河药品股份有限公司 | 活性剂传递系统和保护及施用活性剂的方法 |
| AU2003243605A1 (en) * | 2002-06-13 | 2003-12-31 | Dr. Reddy's Laboratories Limited | 3-'2-(dimethylamino) ethyl!-n-methyl-1h-indole-5-methanesulfonamide and the succinate thereof |
| US20040068000A1 (en) * | 2002-10-02 | 2004-04-08 | Mintong Guo | Compression coated tablets |
| CA2508290C (en) | 2002-12-20 | 2017-02-28 | Ciba Specialty Chemicals Holding Inc. | Synthesis of amines and intermediates for the synthesis thereof |
| PT1575566E (pt) | 2002-12-26 | 2012-03-29 | Pozen Inc | Formas de dosagem em multicamada contendo naproxeno e triptanos |
| US20080213363A1 (en) * | 2003-01-23 | 2008-09-04 | Singh Nikhilesh N | Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa |
| WO2004076403A1 (en) * | 2003-02-24 | 2004-09-10 | Transform Pharmaceuticals, Inc. | Sumatriptan crystalline forms, pharmaceutical compositions and methods |
| KR20060015641A (ko) * | 2003-06-06 | 2006-02-17 | 글락소 그룹 리미티드 | 트립탄 및 ｎｓａｉｄ를 포함하는 조성물 |
| EP1644004A4 (en) * | 2003-06-20 | 2010-10-06 | Ronald Aung-Din | LOCAL THERAPY FOR THE TREATMENT OF MIGRAINS, MUSCLE CLARIFICATIONS, MUSCLE SPASMS, SPASTICITY AND RELATED CONDITIONS |
| JP5563731B2 (ja) * | 2003-09-26 | 2014-07-30 | アルザ・コーポレーシヨン | オピオイドおよび非オピオイド鎮痛薬の制御放出製剤 |
| JP2007506775A (ja) * | 2003-09-26 | 2007-03-22 | アルザ・コーポレーシヨン | 漸増する放出速度を表す制御放出製剤 |
| ATE504288T1 (de) * | 2003-09-26 | 2011-04-15 | Alza Corp | Oros-push-stick für die kontrollierte abgabe von wirkstoffen |
| MXPA06003450A (es) * | 2003-09-26 | 2006-08-31 | Johnson & Johnson | Recubrimiento de farmaco que proporciona alta carga del farmaco y metodos para proporcionar el mismo. |
| EP1765300A2 (en) * | 2004-06-10 | 2007-03-28 | Duramed Pharmaceuticals, Inc. | Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same |
| US8541026B2 (en) * | 2004-09-24 | 2013-09-24 | Abbvie Inc. | Sustained release formulations of opioid and nonopioid analgesics |
| WO2007063418A2 (en) * | 2005-04-13 | 2007-06-07 | Neuraxon, Inc. | Substituted indole compounds having nos inhibitory activity |
| US20070166336A1 (en) * | 2005-12-13 | 2007-07-19 | David Delmarre | Stable and palatable oral liquid sumatriptan compositions |
| EP2010527B1 (en) * | 2006-04-13 | 2013-08-14 | Neuraxon Inc. | 1,5 and 3,6- substituted indole compounds having nos inhibitory activity |
| JP2010507585A (ja) * | 2006-10-19 | 2010-03-11 | オースペックス・ファーマシューティカルズ・インコーポレイテッド | 置換インドール |
| CA2705835A1 (en) * | 2007-11-16 | 2009-05-22 | Neuraxon, Inc. | Indole compounds and methods for treating visceral pain |
| AU2008321353A1 (en) * | 2007-11-16 | 2009-05-22 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Methods for treating visceral pain |
| MX2010005343A (es) * | 2007-11-16 | 2010-08-09 | Neuraxon Inc | Compuestos indola 3, 5-sustituidos que tienen actividad inhibidora de la re-absorcion y el reciclo de nos y norepinefrina. |
| US20090252791A1 (en) * | 2008-04-02 | 2009-10-08 | Venkata Nookaraju Sreedharala | Pharmaceutical compositions comprising a triptan and a nonsteroidal anti-inflammatory drug |
| KR20110019759A (ko) | 2008-05-27 | 2011-02-28 | 비오타 사이언티픽 매니지먼트 피티와이 엘티디 | 항바이러스 염 |
| EP2306998A4 (en) * | 2008-06-20 | 2011-06-15 | Alphapharm Pty Ltd | PHARMACEUTICAL FORMULATION |
| US8592424B2 (en) * | 2008-06-30 | 2013-11-26 | Afgin Pharma Llc | Topical regional neuro-affective therapy |
| NZ599344A (en) | 2009-09-25 | 2015-02-27 | Reddy’S Lab Ltd Dr | Formulations comprising triptan compounds |
| US11337962B2 (en) | 2009-09-25 | 2022-05-24 | Upsher-Smith Laboratories, Llc | Formulations comprising triptan compounds |
| US10383816B2 (en) | 2015-03-02 | 2019-08-20 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with cannabinoid combination products |
| WO2016141056A1 (en) | 2015-03-02 | 2016-09-09 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with cannabinoids |
| US10537554B2 (en) | 2015-08-05 | 2020-01-21 | Upsher-Smith Laboratories, Llc | Pharmaceutical composition for treating migraine |
| RU2751508C2 (ru) | 2016-01-27 | 2021-07-14 | Инстар Текнолоджиз А.С. | Оромукозные нановолоконные носители для терапевтического лечения |
| US20180049994A1 (en) | 2016-08-16 | 2018-02-22 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with caryophyllene |
| EP3766483A1 (en) | 2019-07-19 | 2021-01-20 | BioPharma Synergies, S. L. | Orodispersible powder composition comprising a triptan |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA795239B (en) * | 1978-10-12 | 1980-11-26 | Glaxo Group Ltd | Heterocyclic compounds |
| SE454777B (sv) * | 1980-08-12 | 1988-05-30 | Glaxo Group Ltd | 5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren |
| GB2082175B (en) * | 1980-08-12 | 1984-05-02 | Glaxo Group Ltd | Heterocyclic compounds |
| ZW19381A1 (en) * | 1980-08-12 | 1983-03-09 | Glaxo Group Ltd | Heterocyclic compounds |
| FR2488607A1 (fr) * | 1980-08-12 | 1982-02-19 | Glaxo Group Ltd | Derives de l'indole, leur preparation et leurs utilisations pharmaceutiques |
-
1983
- 1983-06-03 GR GR71558A patent/GR79215B/el unknown
- 1983-06-03 IT IT48422/83A patent/IT1170387B/it active Protection Beyond IP Right Term
- 1983-06-06 DK DK2601/83A patent/DK260183D0/da not_active Application Discontinuation
- 1983-06-07 NL NL8302031A patent/NL193694C/nl not_active IP Right Cessation
- 1983-06-07 KR KR1019830002526A patent/KR900006681B1/ko not_active Expired
- 1983-06-07 IE IE1335/83A patent/IE55358B1/en not_active IP Right Cessation
- 1983-06-07 ZA ZA834110A patent/ZA834110B/xx unknown
- 1983-06-07 LU LU84852A patent/LU84852A1/fr unknown
- 1983-06-07 AT AT0208483A patent/AT381933B/de not_active IP Right Cessation
- 1983-06-07 GB GB08315564A patent/GB2124210B/en not_active Expired
- 1983-06-07 BE BE0/210953A patent/BE896986A/fr not_active IP Right Cessation
- 1983-06-07 FR FR8309429A patent/FR2530625B1/fr not_active Expired
- 1983-06-07 PT PT76830A patent/PT76830B/pt unknown
- 1983-06-07 CH CH3117/83A patent/CH657359A5/fr not_active IP Right Cessation
- 1983-06-07 JP JP58101587A patent/JPS5942366A/ja active Granted
- 1983-06-07 DE DE1993175045 patent/DE19375045I2/de active Active
- 1983-06-07 IL IL68913A patent/IL68913A/xx not_active IP Right Cessation
- 1983-06-07 PH PH29020A patent/PH19908A/en unknown
- 1983-06-07 NZ NZ204482A patent/NZ204482A/en unknown
- 1983-06-07 CA CA000429902A patent/CA1199643A/en not_active Expired
- 1983-06-07 DE DE19833320521 patent/DE3320521A1/de active Granted
- 1983-06-07 ES ES523039A patent/ES523039A0/es active Granted
- 1983-06-07 AU AU15441/83A patent/AU566149B2/en not_active Expired
- 1983-06-07 FI FI832035A patent/FI79530C/fi not_active IP Right Cessation
- 1983-06-07 SE SE8303208A patent/SE452459B/sv not_active IP Right Cessation
-
1984
- 1984-02-16 ES ES529802A patent/ES529802A0/es active Granted
-
1985
- 1985-06-17 ES ES544281A patent/ES8609247A1/es not_active Expired
- 1985-11-15 US US06/789,831 patent/US4816470A/en not_active Expired - Lifetime
-
1987
- 1987-12-30 MY MY179/87A patent/MY8700179A/xx unknown
-
1988
- 1988-09-30 KE KE3833A patent/KE3833A/xx unknown
-
1989
- 1989-02-16 HK HK147/89A patent/HK14789A/xx not_active IP Right Cessation
- 1989-07-21 CY CY1458A patent/CY1458A/en unknown
- 1989-11-20 DO DO4760001989A patent/DOP1989476000A/es unknown
-
1991
- 1991-12-23 SK SK4040-91A patent/SK277877B6/sk unknown
- 1991-12-23 CZ CS914040A patent/CZ280529B6/cs unknown
-
1992
- 1992-06-02 MX MX9202623A patent/MX9202623A/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI79530C (fi) | Foerfarande foer framstaellning av farmakologiskt vaerdefulla 5-aminosulfonylmetyl-indolderivat. | |
| Sugiura et al. | Syntheses and antiinflammatory and hypnotic activity of 5-alkoxy-3-(N-substituted carbamoyl)-1-phenylpyrazoles. 4 | |
| EP1706113B1 (en) | A process for the preparation of 4-(2-dipropylaminoethyl)-1,3-dihydro-2h-indol-2-one hydrochloride | |
| US5464872A (en) | Arylalkyl (thio) amides | |
| EP0242167B1 (en) | Heterocyclic carboxamides | |
| CZ260494A3 (en) | Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon | |
| NL8103769A (nl) | Heterocyclische verbindingen, werkwijze ter bereiding daarvan alsmede farmaceutische preparaten die deze verbindingen als actieve component bevatten. | |
| DK157995B (da) | Analogifremgangsmaade til fremstilling af indolderivater | |
| US4997845A (en) | β-alkylmelatonins as ovulation inhibitors | |
| US4898863A (en) | Heterocyclic carboxamides | |
| CA1299174C (en) | Alkylmelatonins | |
| HU228841B1 (hu) | Eljárás 5-(1-piperazinil)-benzofurán-2-karboxamid elõállítására átmeneti fémkatalizált aminálással | |
| AU2006205697B2 (en) | Novel process for the preparation of substituted indoles | |
| NO124687B (en:Method) | ||
| HU200608B (en) | Process for producing new dihydro-1,4.oxazino(2,3-a)quinoline derivatives and pharmaceutical compositions comprising such compounds | |
| NO162763B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive indol-derivater. | |
| Cruces et al. | New Synthetic Applications of Phenylacotylphenylacetic Acids: A Divergent Synthesis of Benzo-(a) carbazoles and Indolo (2, 1-a)-Isoquinolines | |
| Karp et al. | Preparation and alkylation of regioisomeric tetrahydrophthalimide‐substituted indolin‐2 (3H)‐ones | |
| US6133453A (en) | Method for making substituted indoles | |
| EP0161235A2 (fr) | Nouveaux dérivés de thiénopyridinone, leur procédé de préparation et compositions pharmaceutiques les contenant | |
| DK165976B (da) | 5-aminosulfonyl-methyl-indolderivater og farmaceutiske praeparater med indhold deraf | |
| CA1207777A (en) | Pyrrole-2-acetylamino acid derivatives | |
| HRP20020140A2 (en) | Process for the preparation of o-[cis-4-(-hydroxyethyloxy)cyclohexane-[3h]indol]-2'[1'h]-one derivatives | |
| JPH04330057A (ja) | アニリンアリールスルホン酸アミド類及び薬剤として許容され得るその酸付加塩 | |
| CH516576A (fr) | Procédé de préparation d'un tétrahydrobenzothiénodiazépinone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: GLAXO GROUP LIMITED |