JPH056543B2 - - Google Patents
Info
- Publication number
- JPH056543B2 JPH056543B2 JP59267137A JP26713784A JPH056543B2 JP H056543 B2 JPH056543 B2 JP H056543B2 JP 59267137 A JP59267137 A JP 59267137A JP 26713784 A JP26713784 A JP 26713784A JP H056543 B2 JPH056543 B2 JP H056543B2
- Authority
- JP
- Japan
- Prior art keywords
- difluoro
- cyclopropyl
- formula
- pyrrolidinyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- -1 p-aminobenzyl Chemical group 0.000 claims description 41
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 25
- 239000013078 crystal Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 238000000921 elemental analysis Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 20
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000005457 ice water Substances 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- DJDDYWYYTKNZPM-UHFFFAOYSA-N 2-amino-1,3-dioxane-4,6-dione Chemical compound NC1OC(=O)CC(=O)O1 DJDDYWYYTKNZPM-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000011698 potassium fluoride Substances 0.000 description 3
- 235000003270 potassium fluoride Nutrition 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- MKMDVNZEIQDZEP-UHFFFAOYSA-N 1,2,3,4-tetrafluoro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=C(F)C(F)=C1F MKMDVNZEIQDZEP-UHFFFAOYSA-N 0.000 description 2
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 2
- ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- YBEOYBKKSWUSBR-UHFFFAOYSA-N ethyl 4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)=CNC2=C1 YBEOYBKKSWUSBR-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- JHOHWJIKUDBVDP-UHFFFAOYSA-N 1,2-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(=O)O)=C(F)N(F)C2=C1 JHOHWJIKUDBVDP-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- VBGDNIZEOUSPIR-UHFFFAOYSA-N 7-(3-methylpiperazin-1-yl)-4-oxo-1H-quinoline-3-carboxylic acid hydrochloride Chemical compound Cl.CC1CN(CCN1)C1=CC=C2C(C(=CNC2=C1)C(=O)O)=O VBGDNIZEOUSPIR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-Ethylacetamide Natural products CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- WDTWMEZMHUEZKH-UHFFFAOYSA-N diethyl 2-(aminomethylidene)propanedioate Chemical compound CCOC(=O)C(=CN)C(=O)OCC WDTWMEZMHUEZKH-UHFFFAOYSA-N 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- RSQCSJJCVYLFGV-UHFFFAOYSA-N ethyl 1,2-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C(C)OC(=O)C1=C(N(C2=CC=CC=C2C1=O)F)F RSQCSJJCVYLFGV-UHFFFAOYSA-N 0.000 description 1
- MVJOPRHICXQNLB-UHFFFAOYSA-N ethyl 4-oxo-2,3-dihydro-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)CNC2=C1 MVJOPRHICXQNLB-UHFFFAOYSA-N 0.000 description 1
- PWOYTBYNBYNZCO-UHFFFAOYSA-N ethyl quinoline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)OCC)=CC=C21 PWOYTBYNBYNZCO-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- BEAWFOYVSBYVCD-UHFFFAOYSA-N n-(pyrrolidin-3-ylmethyl)acetamide Chemical compound CC(=O)NCC1CCNC1 BEAWFOYVSBYVCD-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26713784A JPS61143363A (ja) | 1984-12-17 | 1984-12-17 | キノロンカルボン酸誘導体の製造方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26713784A JPS61143363A (ja) | 1984-12-17 | 1984-12-17 | キノロンカルボン酸誘導体の製造方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61143363A JPS61143363A (ja) | 1986-07-01 |
| JPH056543B2 true JPH056543B2 (fi) | 1993-01-26 |
Family
ID=17440591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP26713784A Granted JPS61143363A (ja) | 1984-12-17 | 1984-12-17 | キノロンカルボン酸誘導体の製造方法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61143363A (fi) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6483068A (en) * | 1987-09-25 | 1989-03-28 | Otsuka Pharma Co Ltd | Production of benzo-heterocyclic compound |
| US5039682A (en) * | 1988-06-21 | 1991-08-13 | Pfizer Inc. | 6-fluoro-1,4-dihydroquinol-4-one-3-carboxylic acid derivatives and intermediates therefor |
| WO1992000280A1 (en) * | 1990-06-22 | 1992-01-09 | Nippon Shinyaku Co., Ltd. | Quinoline derivative and production thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51146476A (en) * | 1975-06-06 | 1976-12-16 | Chinoin Gyogyszer Es Vegyeszet | New preparation method of quinolinee33carbonic acid |
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
-
1984
- 1984-12-17 JP JP26713784A patent/JPS61143363A/ja active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51146476A (en) * | 1975-06-06 | 1976-12-16 | Chinoin Gyogyszer Es Vegyeszet | New preparation method of quinolinee33carbonic acid |
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61143363A (ja) | 1986-07-01 |
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