HU184968B - Process for preparing quinolone derivatives - Google Patents
Process for preparing quinolone derivatives Download PDFInfo
- Publication number
- HU184968B HU184968B HU812775A HU277581A HU184968B HU 184968 B HU184968 B HU 184968B HU 812775 A HU812775 A HU 812775A HU 277581 A HU277581 A HU 277581A HU 184968 B HU184968 B HU 184968B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- quinolone
- methyl
- new
- yield
- Prior art date
Links
- 150000007660 quinolones Chemical class 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 238000000034 method Methods 0.000 claims abstract description 19
- -1 methoxy, methylthio Chemical group 0.000 claims abstract description 18
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- GENAIPOCRXECKE-UHFFFAOYSA-N 1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=CC=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 GENAIPOCRXECKE-UHFFFAOYSA-N 0.000 claims description 9
- 150000001450 anions Chemical class 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- 230000002152 alkylating effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 162
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
- 239000000203 mixture Substances 0.000 description 52
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000011928 denatured alcohol Substances 0.000 description 33
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 230000036772 blood pressure Effects 0.000 description 12
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 230000003647 oxidation Effects 0.000 description 12
- 238000007254 oxidation reaction Methods 0.000 description 12
- 150000003462 sulfoxides Chemical class 0.000 description 12
- 150000003568 thioethers Chemical class 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 150000003457 sulfones Chemical class 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000008098 formaldehyde solution Substances 0.000 description 9
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- MDTKNCKPDIOBMH-UHFFFAOYSA-N 1-methyl-3-(methylsulfanylmethyl)-7-(trifluoromethyl)quinolin-4-one Chemical compound FC(F)(F)C1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 MDTKNCKPDIOBMH-UHFFFAOYSA-N 0.000 description 3
- HGYSLLDCNCCEHQ-UHFFFAOYSA-N 1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound C1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 HGYSLLDCNCCEHQ-UHFFFAOYSA-N 0.000 description 3
- HRBXHHMSBOWGSY-UHFFFAOYSA-N 3-(methylsulfonylmethyl)-1h-quinolin-4-one Chemical compound C1=CC=CC2=C(O)C(CS(=O)(=O)C)=CN=C21 HRBXHHMSBOWGSY-UHFFFAOYSA-N 0.000 description 3
- HDPVRRZTNQXTJR-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound ClC1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 HDPVRRZTNQXTJR-UHFFFAOYSA-N 0.000 description 3
- IWWMWAAPKDZCIG-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 IWWMWAAPKDZCIG-UHFFFAOYSA-N 0.000 description 3
- PAJPXBASGXTLSS-UHFFFAOYSA-N 7-ethyl-1h-quinolin-4-one Chemical compound OC1=CC=NC2=CC(CC)=CC=C21 PAJPXBASGXTLSS-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- WHMKOLHSNXZCAV-UHFFFAOYSA-N 1,7-dimethyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound CN1C=C(CS(C)(=O)=O)C(=O)C=2C1=CC(C)=CC=2 WHMKOLHSNXZCAV-UHFFFAOYSA-N 0.000 description 2
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 2
- ULBQLDYBBSPRAO-UHFFFAOYSA-N 1-methyl-3-(methylsulfinylmethyl)quinolin-4-one Chemical compound C1=CC=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 ULBQLDYBBSPRAO-UHFFFAOYSA-N 0.000 description 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 2
- 229940093475 2-ethoxyethanol Drugs 0.000 description 2
- CQKLDECUWZDOAW-UHFFFAOYSA-N 3-(chloromethyl)-1-methyl-7-(trifluoromethyl)quinolin-4-one;hydrochloride Chemical compound Cl.C1=C(C(F)(F)F)C=C2N(C)C=C(CCl)C(=O)C2=C1 CQKLDECUWZDOAW-UHFFFAOYSA-N 0.000 description 2
- GQVBDXKXBACRJS-UHFFFAOYSA-N 3-(chloromethyl)-1-methylquinolin-4-one;hydrochloride Chemical compound Cl.C1=CC=C2N(C)C=C(CCl)C(=O)C2=C1 GQVBDXKXBACRJS-UHFFFAOYSA-N 0.000 description 2
- FQTXHTJQYTUEJG-UHFFFAOYSA-N 3-(hydroxymethyl)-1-methyl-7-(trifluoromethyl)quinolin-4-one Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(CO)C(=O)C2=C1 FQTXHTJQYTUEJG-UHFFFAOYSA-N 0.000 description 2
- YOGIENHSLIMXBF-UHFFFAOYSA-N 3-(hydroxymethyl)-7-(trifluoromethyl)-1h-quinolin-4-one Chemical compound FC(F)(F)C1=CC=C2C(=O)C(CO)=CNC2=C1 YOGIENHSLIMXBF-UHFFFAOYSA-N 0.000 description 2
- JTQOWYDPSFLWCP-UHFFFAOYSA-N 3-(methylsulfinylmethyl)-1h-quinolin-4-one Chemical compound C1=CC=CC2=C(O)C(CS(=O)C)=CN=C21 JTQOWYDPSFLWCP-UHFFFAOYSA-N 0.000 description 2
- KAGQRUNOAPAMCZ-UHFFFAOYSA-N 4-chloro-3-(chloromethyl)quinoline Chemical class C1=CC=CC2=C(Cl)C(CCl)=CN=C21 KAGQRUNOAPAMCZ-UHFFFAOYSA-N 0.000 description 2
- UVBNWRMZMQJLKE-UHFFFAOYSA-N 4-chloro-3-(methylsulfonylmethyl)quinoline Chemical compound C1=CC=CC2=C(Cl)C(CS(=O)(=O)C)=CN=C21 UVBNWRMZMQJLKE-UHFFFAOYSA-N 0.000 description 2
- ZJGHSMMIYGZJJV-UHFFFAOYSA-N 6-fluoro-1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound C1=C(F)C=C2C(=O)C(CSC)=CN(C)C2=C1 ZJGHSMMIYGZJJV-UHFFFAOYSA-N 0.000 description 2
- NHXDXHBIMREAMF-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfinylmethyl)quinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 NHXDXHBIMREAMF-UHFFFAOYSA-N 0.000 description 2
- AXVWDWUHKASFBZ-UHFFFAOYSA-N 7-ethyl-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound OC1=C(C(O)=O)C=NC2=CC(CC)=CC=C21 AXVWDWUHKASFBZ-UHFFFAOYSA-N 0.000 description 2
- XDTQCQCYYCBTDO-UHFFFAOYSA-N 7-fluoro-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=C(F)C=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 XDTQCQCYYCBTDO-UHFFFAOYSA-N 0.000 description 2
- DAVZFKTUWRBWKI-UHFFFAOYSA-N 7-tert-butyl-1h-quinolin-4-one Chemical compound OC1=CC=NC2=CC(C(C)(C)C)=CC=C21 DAVZFKTUWRBWKI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- 241000124008 Mammalia Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 210000001367 artery Anatomy 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
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- WKXFRVQZQAOGPX-UHFFFAOYSA-N ethyl 7-ethyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(CC)C=CC2=C(O)C(C(=O)OCC)=CN=C21 WKXFRVQZQAOGPX-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- XGJVFWBHYJQTDM-UHFFFAOYSA-N 1,6-dimethyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound C1=C(C)C=C2C(=O)C(CSC)=CN(C)C2=C1 XGJVFWBHYJQTDM-UHFFFAOYSA-N 0.000 description 1
- URMXOBOURDLDFR-UHFFFAOYSA-N 1,6-dimethyl-3-(methylsulfinylmethyl)quinolin-4-one Chemical compound CN1C=C(CS(C)=O)C(=O)C2=CC(C)=CC=C21 URMXOBOURDLDFR-UHFFFAOYSA-N 0.000 description 1
- YYDXBHUFXKTMTQ-UHFFFAOYSA-N 1,6-dimethyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound CN1C=C(CS(C)(=O)=O)C(=O)C2=CC(C)=CC=C21 YYDXBHUFXKTMTQ-UHFFFAOYSA-N 0.000 description 1
- BNMIHAXCMFXSIJ-UHFFFAOYSA-N 1,7-dimethyl-3-(methylsulfonylmethyl)quinoline-4-thione Chemical compound CN1C=C(CS(C)(=O)=O)C(=S)C=2C1=CC(C)=CC=2 BNMIHAXCMFXSIJ-UHFFFAOYSA-N 0.000 description 1
- HXQLLNRTDQHYAT-UHFFFAOYSA-N 1-ethyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=CC=C2N(CC)C=C(CS(C)(=O)=O)C(=O)C2=C1 HXQLLNRTDQHYAT-UHFFFAOYSA-N 0.000 description 1
- AGEVWYPZSUUXCB-UHFFFAOYSA-N 1-methyl-3-(methylsulfinylmethyl)-7-(trifluoromethyl)quinolin-4-one Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 AGEVWYPZSUUXCB-UHFFFAOYSA-N 0.000 description 1
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- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 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
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- WMAKDXJLYZPTGQ-UHFFFAOYSA-N ethyl 7-tert-butyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(C(C)(C)C)C=CC2=C(O)C(C(=O)OCC)=CN=C21 WMAKDXJLYZPTGQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- A61P9/12—Antihypertensives
-
- 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
- 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
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- 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
- C07D215/36—Sulfur 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8031106 | 1980-09-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
HU184968B true HU184968B (en) | 1984-11-28 |
Family
ID=10516302
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU812775A HU184968B (en) | 1980-09-26 | 1981-09-25 | Process for preparing quinolone derivatives |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS5785369A (enrdf_load_stackoverflow) |
BE (1) | BE890477A (enrdf_load_stackoverflow) |
HU (1) | HU184968B (enrdf_load_stackoverflow) |
ZA (1) | ZA816352B (enrdf_load_stackoverflow) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03196382A (ja) * | 1989-12-26 | 1991-08-27 | Nec Home Electron Ltd | 携帯型情報処理装置 |
-
1981
- 1981-09-14 ZA ZA816352A patent/ZA816352B/xx unknown
- 1981-09-24 BE BE0/206048A patent/BE890477A/fr not_active IP Right Cessation
- 1981-09-25 HU HU812775A patent/HU184968B/hu unknown
- 1981-09-25 JP JP56151895A patent/JPS5785369A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS6348268B2 (enrdf_load_stackoverflow) | 1988-09-28 |
JPS5785369A (en) | 1982-05-28 |
ZA816352B (en) | 1982-09-29 |
BE890477A (fr) | 1982-03-24 |
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