DK141700B - Analogifremgangsmåde til fremstilling af cinchonin- eller cinchonidinderivater. - Google Patents
Analogifremgangsmåde til fremstilling af cinchonin- eller cinchonidinderivater. Download PDFInfo
- Publication number
- DK141700B DK141700B DK637674AA DK637674A DK141700B DK 141700 B DK141700 B DK 141700B DK 637674A A DK637674A A DK 637674AA DK 637674 A DK637674 A DK 637674A DK 141700 B DK141700 B DK 141700B
- Authority
- DK
- Denmark
- Prior art keywords
- trifluoromethyl
- bis
- chloro
- mixture
- ethyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 29
- 238000000034 method Methods 0.000 title claims description 17
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical class C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 title claims description 12
- KMPWYEUPVWOPIM-QAMTZSDWSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-QAMTZSDWSA-N 0.000 title claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 152
- 150000001875 compounds Chemical class 0.000 claims description 63
- WFJNHVWTKZUUTR-UHFFFAOYSA-N dihydrocinchonidine Natural products C1=CC=C2C(C(O)C3CC4CCN3CC4CC)=CC=NC2=C1 WFJNHVWTKZUUTR-UHFFFAOYSA-N 0.000 claims description 61
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 29
- WFJNHVWTKZUUTR-KODHJQJWSA-N (r)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-quinolin-4-ylmethanol Chemical compound C1=CC=C2C([C@@H](O)[C@@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 WFJNHVWTKZUUTR-KODHJQJWSA-N 0.000 claims description 27
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 20
- 229920002554 vinyl polymer Polymers 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 11
- 101100139845 Caenorhabditis elegans rac-2 gene Proteins 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 132
- 239000000243 solution Substances 0.000 description 80
- 239000000203 mixture Substances 0.000 description 75
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 238000003756 stirring Methods 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 30
- 229910002027 silica gel Inorganic materials 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 235000011152 sodium sulphate Nutrition 0.000 description 28
- 238000004587 chromatography analysis Methods 0.000 description 25
- -1 2,4-bis (trifluoromethyl) -4-bromoquinoline Chemical compound 0.000 description 24
- 238000001953 recrystallisation Methods 0.000 description 23
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- WFJNHVWTKZUUTR-QAMTZSDWSA-N Hydrocinchonine Chemical compound C1=CC=C2C([C@H](O)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 WFJNHVWTKZUUTR-QAMTZSDWSA-N 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000007858 starting material Substances 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- 150000003248 quinolines Chemical class 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 229930195733 hydrocarbon Natural products 0.000 description 11
- 150000002430 hydrocarbons Chemical group 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 239000004215 Carbon black (E152) Substances 0.000 description 9
- ULGGPDHVFPOYQP-UHFFFAOYSA-N chloroform;n,n-diethylethanamine;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl.CCN(CC)CC ULGGPDHVFPOYQP-UHFFFAOYSA-N 0.000 description 9
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- DXALAFAFIXJDOS-UHFFFAOYSA-N 4-bromo-2,8-bis(trifluoromethyl)quinoline Chemical compound C1=CC=C(C(F)(F)F)C2=NC(C(F)(F)F)=CC(Br)=C21 DXALAFAFIXJDOS-UHFFFAOYSA-N 0.000 description 8
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- ZJZPFKHDRYBYBO-UHFFFAOYSA-N 7-chloro-2-(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=C(Cl)C=C2NC(C(F)(F)F)=CC(=O)C2=C1 ZJZPFKHDRYBYBO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000011877 solvent mixture Substances 0.000 description 6
- SUNAMHNJYSQUPL-UHFFFAOYSA-N 2-(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=CC=C2NC(C(F)(F)F)=CC(=O)C2=C1 SUNAMHNJYSQUPL-UHFFFAOYSA-N 0.000 description 5
- JRTGGNDDSKKPQE-UHFFFAOYSA-N 4-bromo-2-(trifluoromethyl)quinoline Chemical compound C1=CC=CC2=NC(C(F)(F)F)=CC(Br)=C21 JRTGGNDDSKKPQE-UHFFFAOYSA-N 0.000 description 5
- DUKCYQIYQNHEEU-UHFFFAOYSA-N 4-bromo-7-chloro-2-(trifluoromethyl)quinoline Chemical compound C1=CC(Cl)=CC2=NC(C(F)(F)F)=CC(Br)=C21 DUKCYQIYQNHEEU-UHFFFAOYSA-N 0.000 description 5
- ZEXFUTKZNOQJSQ-UHFFFAOYSA-N 4-bromo-8-chloro-2-(trifluoromethyl)quinoline Chemical compound C1=CC=C(Cl)C2=NC(C(F)(F)F)=CC(Br)=C21 ZEXFUTKZNOQJSQ-UHFFFAOYSA-N 0.000 description 5
- HXHHICRJVIALFX-UHFFFAOYSA-N 5-chloro-2-(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=CC(Cl)=C2C(O)=CC(C(F)(F)F)=NC2=C1 HXHHICRJVIALFX-UHFFFAOYSA-N 0.000 description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- YDQJXVYGARVLRT-UHFFFAOYSA-N Lepidine Natural products C=1C=CC(CC=2NC=CN=2)=CC=1OC=1C(OC)=CC=CC=1CC1=NC=CN1 YDQJXVYGARVLRT-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000020176 deacylation Effects 0.000 description 4
- 238000005947 deacylation reaction Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- DOCZCYFBVOIVFX-UHFFFAOYSA-N 2,5-bis(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=CC=C2NC(C(F)(F)F)=CC(=O)C2=C1C(F)(F)F DOCZCYFBVOIVFX-UHFFFAOYSA-N 0.000 description 3
- JXUPSVUIPXTWMN-UHFFFAOYSA-N 4-bromo-5-chloro-2-(trifluoromethyl)quinoline Chemical compound ClC1=CC=CC2=NC(C(F)(F)F)=CC(Br)=C21 JXUPSVUIPXTWMN-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 101100441092 Danio rerio crlf3 gene Proteins 0.000 description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
- 241000224017 Plasmodium berghei Species 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- WDJQAYUPVJEQJW-UHFFFAOYSA-N chloroform;n,n-diethylethanamine;methanol Chemical compound OC.ClC(Cl)Cl.CCN(CC)CC WDJQAYUPVJEQJW-UHFFFAOYSA-N 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- SJNVVYLZZUSUDI-HKUYNNGSSA-N 1-[(3R,4S)-1-benzoyl-3-ethylpiperidin-4-yl]-3-[2,8-bis(trifluoromethyl)quinolin-4-yl]propan-2-one Chemical class FC(C1=NC2=C(C=CC=C2C(=C1)CC(C[C@H]1[C@H](CN(CC1)C(C1=CC=CC=C1)=O)CC)=O)C(F)(F)F)(F)F SJNVVYLZZUSUDI-HKUYNNGSSA-N 0.000 description 2
- NPMAASFLXZLSHY-STQMWFEESA-N 1-[2,8-bis(trifluoromethyl)quinolin-4-yl]-3-[(3R,4S)-3-ethylpiperidin-4-yl]propan-2-one Chemical compound FC(C1=NC2=C(C=CC=C2C(=C1)CC(C[C@H]1[C@H](CNCC1)CC)=O)C(F)(F)F)(F)F NPMAASFLXZLSHY-STQMWFEESA-N 0.000 description 2
- KBTXVMVBORZGOL-UHFFFAOYSA-N 2,7-bis(trifluoromethyl)-1h-quinolin-4-one Chemical compound N1C(C(F)(F)F)=CC(=O)C=2C1=CC(C(F)(F)F)=CC=2 KBTXVMVBORZGOL-UHFFFAOYSA-N 0.000 description 2
- ICOTWQFECIUUHC-UHFFFAOYSA-N 4-bromo-2,7-bis(trifluoromethyl)quinoline Chemical compound BrC1=CC(C(F)(F)F)=NC2=CC(C(F)(F)F)=CC=C21 ICOTWQFECIUUHC-UHFFFAOYSA-N 0.000 description 2
- SBVZSZNYPRWWNN-UHFFFAOYSA-N 8-chloro-2-(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=CC(Cl)=C2NC(C(F)(F)F)=CC(=O)C2=C1 SBVZSZNYPRWWNN-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 239000003430 antimalarial agent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- WCIHGUTYEXLBLC-UHFFFAOYSA-N n,n-diethylethanamine;propan-2-one Chemical compound CC(C)=O.CCN(CC)CC WCIHGUTYEXLBLC-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- CSMXHZYOXJSYFA-CTERPIQNSA-N (2r)-1,1-dichloro-3-[(3r,4s)-3-ethylpiperidin-4-yl]propan-2-ol;hydrochloride Chemical compound Cl.CC[C@H]1CNCC[C@H]1C[C@@H](O)C(Cl)Cl CSMXHZYOXJSYFA-CTERPIQNSA-N 0.000 description 1
- KPHXIHBHDJNUJE-YWUTZLAHSA-N (2s)-1,1-dichloro-3-[(3r,4s)-3-ethenylpiperidin-4-yl]propan-2-ol;hydrochloride Chemical compound Cl.ClC(Cl)[C@@H](O)C[C@@H]1CCNC[C@@H]1C=C KPHXIHBHDJNUJE-YWUTZLAHSA-N 0.000 description 1
- 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 1
- SHXHPUAKLCCLDV-UHFFFAOYSA-N 1,1,1-trifluoropentane-2,4-dione Chemical compound CC(=O)CC(=O)C(F)(F)F SHXHPUAKLCCLDV-UHFFFAOYSA-N 0.000 description 1
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 1
- JIWHKBAFGFPZKM-UHFFFAOYSA-N 2,8-bis(trifluoromethyl)-1h-quinolin-4-one Chemical compound C1=CC=C2C(O)=CC(C(F)(F)F)=NC2=C1C(F)(F)F JIWHKBAFGFPZKM-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- VBLXCTYLWZJBKA-UHFFFAOYSA-N 2-(trifluoromethyl)aniline Chemical compound NC1=CC=CC=C1C(F)(F)F VBLXCTYLWZJBKA-UHFFFAOYSA-N 0.000 description 1
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- LIQBKSIZAXKCPA-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxobutanoic acid Chemical compound OC(=O)CC(=O)C(F)(F)F LIQBKSIZAXKCPA-UHFFFAOYSA-N 0.000 description 1
- MMGGMYXSOLZCBK-UHFFFAOYSA-N 4-bromo-2,3-bis(trifluoromethyl)quinoline Chemical compound C1=CC=C2C(Br)=C(C(F)(F)F)C(C(F)(F)F)=NC2=C1 MMGGMYXSOLZCBK-UHFFFAOYSA-N 0.000 description 1
- POZSAJHQRSOUOI-UHFFFAOYSA-N 4-bromo-2,5-bis(trifluoromethyl)quinoline Chemical compound FC(F)(F)C1=CC=CC2=NC(C(F)(F)F)=CC(Br)=C21 POZSAJHQRSOUOI-UHFFFAOYSA-N 0.000 description 1
- XBWOMWBSPFAUEL-UHFFFAOYSA-N 4-bromo-6-chloro-2-(trifluoromethyl)quinoline Chemical compound C1=C(Cl)C=CC2=NC(C(F)(F)F)=CC(Br)=C21 XBWOMWBSPFAUEL-UHFFFAOYSA-N 0.000 description 1
- SUXIPCHEUMEUSV-UHFFFAOYSA-N 4-bromoquinoline Chemical compound C1=CC=C2C(Br)=CC=NC2=C1 SUXIPCHEUMEUSV-UHFFFAOYSA-N 0.000 description 1
- 150000005650 4-bromoquinolines Chemical class 0.000 description 1
- 150000005637 4-haloquinolines Chemical class 0.000 description 1
- 150000004331 4-hydroxyquinolines Chemical class 0.000 description 1
- MGEMMMJZAWYWNI-UHFFFAOYSA-N 6-chloro-2-(trifluoromethyl)-1h-quinolin-4-one Chemical compound ClC1=CC=C2NC(C(F)(F)F)=CC(=O)C2=C1 MGEMMMJZAWYWNI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-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 compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- CTUYBUXNBUTGOW-UHFFFAOYSA-N C1=CC=C2C([Li])=CC(C(F)(F)F)=NC2=C1C(F)(F)F Chemical compound C1=CC=C2C([Li])=CC(C(F)(F)F)=NC2=C1C(F)(F)F CTUYBUXNBUTGOW-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- PKSROMPNLONTJT-UHFFFAOYSA-N azanium;chloroform;methanol;hydroxide Chemical compound N.O.OC.ClC(Cl)Cl PKSROMPNLONTJT-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- WVHBHPATSLQXGC-UHFFFAOYSA-N benzene;ethanol Chemical compound CCO.C1=CC=CC=C1 WVHBHPATSLQXGC-UHFFFAOYSA-N 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- MMFVFNVXXDFELX-UHFFFAOYSA-N chloroform;n,n-diethylethanamine Chemical compound ClC(Cl)Cl.CCN(CC)CC MMFVFNVXXDFELX-UHFFFAOYSA-N 0.000 description 1
- OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000011953 free-radical catalyst Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LUMVCLJFHCTMCV-UHFFFAOYSA-M potassium;hydroxide;hydrate Chemical compound O.[OH-].[K+] LUMVCLJFHCTMCV-UHFFFAOYSA-M 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
- C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42264573A | 1973-12-07 | 1973-12-07 | |
| US42264573 | 1973-12-07 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK637674A DK637674A (enrdf_load_stackoverflow) | 1975-07-28 |
| DK141700B true DK141700B (da) | 1980-05-27 |
| DK141700C DK141700C (enrdf_load_stackoverflow) | 1980-12-08 |
Family
ID=23675777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK637674AA DK141700B (da) | 1973-12-07 | 1974-12-06 | Analogifremgangsmåde til fremstilling af cinchonin- eller cinchonidinderivater. |
Country Status (17)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2381044A1 (fr) * | 1977-02-17 | 1978-09-15 | Hoffmann La Roche | Procede pour la preparation de mefloquine |
| HU191508B (en) * | 1982-12-02 | 1987-02-27 | Alkaloida Vegyeszeti Gyar,Hu | Process for preparing new chloromethyl-quinoline derivatives |
| AU9740998A (en) * | 1997-09-08 | 1999-03-29 | F. Hoffmann-La Roche Ag | Piperidine derivatives against malaria |
| JP2002360830A (ja) * | 2001-06-04 | 2002-12-17 | Heiwa Corp | 球貯蔵入賞装置 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1217427A (en) * | 1967-12-21 | 1970-12-31 | America Home Products Corp | Cinchona alkaloid derivatives |
| CH590275A5 (enrdf_load_stackoverflow) * | 1970-03-16 | 1977-07-29 | Hoffmann La Roche | |
| IL38492A (en) * | 1971-01-07 | 1975-08-31 | Sparamedica Ag | Quinoline derivatives,their preparation and pharmaceutical compositions containing them |
-
1974
- 1974-11-30 CH CH1586274A patent/CH605916A5/xx not_active IP Right Cessation
- 1974-12-02 PH PH16586A patent/PH10837A/en unknown
- 1974-12-02 ZA ZA00747664A patent/ZA747664B/xx unknown
- 1974-12-03 SE SE7415160A patent/SE415100B/xx unknown
- 1974-12-04 IL IL46181A patent/IL46181A/xx unknown
- 1974-12-05 CA CA215,292A patent/CA1039283A/en not_active Expired
- 1974-12-05 FR FR7439824A patent/FR2292476A1/fr active Granted
- 1974-12-06 BE BE151217A patent/BE823023A/xx unknown
- 1974-12-06 NL NL7415931A patent/NL7415931A/xx not_active Application Discontinuation
- 1974-12-06 JP JP49140423A patent/JPS5088076A/ja active Pending
- 1974-12-06 DK DK637674AA patent/DK141700B/da unknown
- 1974-12-06 GB GB5284374A patent/GB1441519A/en not_active Expired
- 1974-12-06 BR BR10249/74A patent/BR7410249A/pt unknown
- 1974-12-06 AT AT977974A patent/AT339310B/de not_active IP Right Cessation
- 1974-12-09 DE DE19742458146 patent/DE2458146A1/de not_active Withdrawn
-
1977
- 1977-01-18 AT AT24577A patent/AT353792B/de not_active IP Right Cessation
- 1977-03-30 KE KE2718A patent/KE2718A/xx unknown
- 1977-12-30 MY MY239/77A patent/MY7700239A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE7415160L (enrdf_load_stackoverflow) | 1975-06-09 |
| ZA747664B (en) | 1976-01-28 |
| ATA24577A (de) | 1979-05-15 |
| CA1039283A (en) | 1978-09-26 |
| NL7415931A (nl) | 1975-06-10 |
| AU7559274A (en) | 1976-05-27 |
| BR7410249A (pt) | 1976-06-29 |
| PH10837A (en) | 1977-09-09 |
| DE2458146A1 (de) | 1975-06-12 |
| FR2292476B1 (enrdf_load_stackoverflow) | 1979-05-18 |
| SE415100B (sv) | 1980-09-08 |
| AT353792B (de) | 1979-12-10 |
| IL46181A0 (en) | 1975-03-13 |
| JPS5088076A (enrdf_load_stackoverflow) | 1975-07-15 |
| ATA977974A (de) | 1977-02-15 |
| MY7700239A (en) | 1977-12-31 |
| FR2292476A1 (fr) | 1976-06-25 |
| KE2718A (en) | 1977-07-15 |
| GB1441519A (en) | 1976-07-07 |
| DK637674A (enrdf_load_stackoverflow) | 1975-07-28 |
| DK141700C (enrdf_load_stackoverflow) | 1980-12-08 |
| IL46181A (en) | 1978-03-10 |
| AT339310B (de) | 1977-10-10 |
| BE823023A (fr) | 1975-06-06 |
| CH605916A5 (enrdf_load_stackoverflow) | 1978-10-13 |
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