CN1031190C - 喹啉羧酸衍生物的制备方法 - Google Patents
喹啉羧酸衍生物的制备方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 34
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- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
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- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 claims 1
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- 150000001342 alkaline earth metals Chemical class 0.000 description 2
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
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- 238000001816 cooling Methods 0.000 description 2
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- 150000002576 ketones Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- DTYLXDLAOLOTKT-UHFFFAOYSA-N 1,4-dihydroquinoline-3-carboxylic acid Chemical class C1=CC=C2CC(C(=O)O)=CNC2=C1 DTYLXDLAOLOTKT-UHFFFAOYSA-N 0.000 description 1
- 239000005968 1-Decanol Substances 0.000 description 1
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 229910001038 basic metal oxide Inorganic materials 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 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
- -1 cyclic amine Chemical class 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000012971 dimethylpiperazine Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000005451 methyl sulfates Chemical class 0.000 description 1
- 229950000081 metilsulfate Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及一种新的制备通式(I)化合物(R1和R2代表氢或C1-4烷基，R2代表C1-4烷基，R4、R5和R6代表氢或卤素)及其药用盐的方法。通式(I)化合物是已知的抗菌剂。该方法的优点在于制备过程简单，产率高，反应时间短。
Description
本发明涉及一种新的制备具有通式(I)的1-(可卤代)-乙基-7-(3，4，5-取代的哌嗪)-6，8-二氟-4-氧-1，4-二氢-喹啉-3-羧酸衍生物及其药用盐的方法。
在通式(I)中，R1和R3代表氢或C1-4烷基，R2代表C1-4烷基，R4、R5和R6代表氢或卤素。
已知一类具有通式(I)的7-(3，4，5-取代的哌嗪)-喹啉-3-羧酸衍生物具有高抗菌活性(见Antimicrob.Agents Chemother 1987，31，854；Drugs of Fut.1986，11，578 26thInterscci.Conf，Antimicrob.AgentsChemother，1986，Abst.430-431；25thIntersci.Conf.Antimicrob.AgentsChemother.1985，567)。可通过使6，7，8-三氟-4-氧-1，4-二氢-喹啉-3-羧酸与环胺反应来制备这些化合物(见德国专利说明书3433924，日本专利说明书60142980、6185381和6165882)。
本发明提供了一种新的制备具有通式(I)(其中R1和R3代表氢或C1-4烷基，R2代表C1-4烷基，R4、R5和R6代表氢或卤素)的喹啉-3-羧酸衍生物及其药用盐的方法，该方法包括使具有通式(II)的化合物：(其中R代表卤素、含有2-6个碳原子的脂族酰氧基或含有7-11个碳原子的芳族酰氧基，R4、R5和R6的定义与上述相同)与具有通式(III)的胺：(其中R1、R2和R3的定义与上述相同)或其盐反应，而且在分离之后(或不分离)，将反应得到的通式(IV)化合物：
(其中R、R1、R2、R3、R4、R5和R6的定义与上述相同)水解，如果需要，将由此得到的通式(I)化合物转化为其盐，或者不转化为盐。
本发明方法的优点在于能使通式(I)化合物的制备简化，产率高且反应时间短。
具有通式(IV)的硼衍生物是新的化合物。
根据优选的本发明方法的实施方案，直接将通式(IV)硼衍生物转化为所需的通式(I)喹啉-3-羧酸而无需分离。
如果需要，可在惰性有机溶剂和酸结合剂的存在下使通式(II)硼衍生物与通式(III)胺反应。
惰性有机溶剂优选酰胺(例如二甲基甲酰胺、二甲基乙酰胺)、酮(例如丙酮、甲乙酮)、醚(例如二噁烷、四氢呋喃、乙醚)、酯(例如乙酸乙酯、乙酸甲酯、丙酸乙酯)、亚砜(例如二甲基亚砜)、醇(例如甲醇、乙醇、1-癸醇、丁醇)、腈(例如乙腈)和卤代有机溶剂(例如氯仿、二氯乙烷)。
有机或无机碱可用作酸结合剂。在有机碱中，可以列举三烷基胺(例如三乙胺、三丁胺)、环胺(例如吡啶、1，5-二氮双环[5.4.0]十一碳-5-烯、1，5-二氮双环[4.3.0]壬-5-烯、1，4-二氮双环[2.2.2]辛烷)；无机碱优选碱金属或碱土金属的氢氧化物或碳酸盐。因此，可有利地采用碳酸钾、碳酸氢钾、氢氧化钠、氢氧化钙等或过量的通式(III)胺作为酸结合剂。
根据所用的溶剂，通式(II)硼衍生物与通式(III)胺的反应可在10-200℃下进行。反应时间在0.1-10小时范围内。反应时间还取决于反应温度。如果反应在较高的温度下进行，可以缩短反应时间。上述反应条件均为优选值，也可以采用其它反应条件。
可在分离之后(也可以不经分离)，在酸性或碱性条件下将通式(IV)化合物水解为所需的通式(I)喹啉-3-羧酸。如果需要，可通过例如冷却使通式(IV)化合物从反应混合物中沉淀出来，而且可通过例如过滤或离心将其分离出来。
可通过在碱金属或碱土金属氢氧化物或碳酸盐的水溶液中加热进行碱性水解。优选使用氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、氢氧化钙的水溶液。但是，在水解步骤中还可使用有机胺(例如二乙胺)。
可在无机酸水溶液中进行酸性水解。一种优选的方法是在盐酸、溴化氢、硫酸或磷酸水溶液中加热，使通式(IV)化合物水解。还可在有机酸(例如乙酸，丙酸等)中进行水解。
通式(IV)化合物的水解还可在能与水混溶的有机溶剂的存在下于水性介质中进行。例如醇(例如甲醇、乙醇)、酮(例如丙酮)、醚(例如二噁烷)、酰胺(例如二甲基甲酰胺)、亚砜(例如二甲基亚砜)或吡啶可用于此目的。
可通过例如将水溶液的pH值调节到一个适当的值并通过例如过滤或离心分离析出的结晶，或者通过含水反应混合物的冷冻干燥，将由此得到的通式(I)喹啉-3-羧酸分离出来。
可用已知的方法将通式(I)化合物转化为其药用盐。优选形成酸加成盐，例如与卤代氢、磺酸、硫酸、或有机酸形成的盐。可形成氯化物、溴化物、芳基磺酸盐、甲基磺酸盐、马来酸盐、富马酸盐、苯甲酸盐等。通式(I)化合物可与碱金属或碱土金属或其它金属离子等形成盐。因此，可制备钠盐、钾盐、镁盐、银盐及铜盐等。
可用已知方法将通式(I)化合物及其药用盐转化为水合物(例如半水合物、三水合物等)。
本发明进一步提供一种具有通式(IV)(其中R、R1、R2、R3、R4、R5和R6的定义与上述相同)的新化合物。
具有通式(II)的原料可根据下述方法制备：使1-乙基-6，7，8-三氟-4-氧-1，4-二氢-喹啉-3-羧酸(英国专利说明书2,057,440)与一种硼衍生物[例如具有通式(V)的化合物：(其中R为卤素、含有2-6个碳原子的脂族酰氧基或含有7-11个碳原子的芳族酰氧基)]或氟硼酸在水或有机介质中反应。
在下述实施例中给出了本发明的其它细节，但这些实施例不能限制本发明的保护范围。
实施例1
使31.9g(1-乙基-6，7，8-三氟-1，4-二氢-4-氧-喹啉-3-羧离子-O3-O4)-二氟-硼与57.1g2，6-二甲基-哌嗪于150ml二甲基亚砜中在100℃下反应3小时。加入400ml3％(w/v)氢氧化钠水溶液，加热2小时进行水解。过滤反应混合物，用96％(w/v)乙酸将pH值调至7。将结晶的反应混合物通霄冷却，滤出析出的晶体，用水洗涤并干燥。得到29.9g 7-[3，5-二甲基-哌嗪子基]1-乙基-6，8-二氟-1，4-二氢-4-氧-喹啉-3-羧酸。M.p.＝232-234℃。
分子式C17H19F2N3O3的元素分析：
计算值；C＝59.17％H＝5.80％N＝11.49％
实测值：C＝59.05％H＝5.91％N＝11.45％
实施例2
按照实施例1所述的方法，使31.9g(1-乙基-6，7，8-三氟-1，4-二氢-4-氧-喹啉-3-羧离子-O3-O4)-二氟-硼与50.1g2-甲基-哌嗪于150ml二甲基亚砜中反应。得到30.6gl-乙基-6，8-二氟1，4-二氢-4-氧-7-(3-甲基-哌嗪子基)-喹啉-3-羧酸。M.p.＝238-240℃。
分子式C17H19F2N3O3的元素分析：
计算值：C＝58.11％H＝5.45％N＝11.96％
实测值：C＝58.01％H＝5.55％N＝12.07％
实施例3
按照实施例1所述的方法，使39.9g(1-乙基-6，7，8-三氟-1，4-二氢-4-氧-喹啉-3-羧离子-O3，O4)-双-(乙酸离子-O)-硼与50.1g2-甲基-哌嗪于150ml二甲基亚砜中反应。得到30.2g 1-乙基-6，8-二氟-1，4-二氢-4-氧-7-(3-甲基-哌嗪子基)-喹啉-3-羧酸。M.p.＝237-239℃。
分子式C17H19F2N3O3的元素分析：
计算值：C＝50.11％H＝5.45％N＝11.96％
实测值：C＝57.97％H＝5.53％N＝11.90％
实施例4
按照实施例1所述的方法，使42.7g(1-乙基-6，7，8-三氟-1，4-二氢-4-氧-喹啉-3-羧离子-O3，O4)-双-(丙酸离子-O)-硼与50.1g 2-甲基-哌嗪反应。得到28.7g1-乙基-6，8-二氟-1，4-二氢-4-氧-7-(3-甲基-哌嗪子基)-喹啉-3-羧酸。M.p.＝237-239℃。
分子式C17H19F2N3O3的元素分析：
计算值： C＝58.11％H＝5.45％N＝11.96％
实测值： C＝57.99％H＝5.52％N＝12.10％
Claims (9)
1.一种制备通式(I)化合物及其药用盐的方法，其中R1和R3代表氢或C1-4烷基，R2代表C1-4烷基，R4、R5和R6代表氢或卤素，
该方法包括使通式(II)化合物在低温下，
其中R代表卤素、含2-6个碳原子的脂族酰氧基或含7-11个碳原子的芳族酰氧基，R4、R5和R6的定义与上述相同，
与通式(III)哌嗪衍生物或其盐反应，
其中R1、R2和R3的定义与上述相同，
而且在分离之后或不经分离，将反应得到的通式(IV)化合物进行水解，
其中R、R1、R2、R3、R4、R5和R6的定义与上述相同，
如果需要，将由此得到的通式(I)化合物转化为其盐，或者不将其转化为盐。
2.权利要求1所述的方法，该方法包括在有机溶剂的存在下，使通式(II)化合物与通式(III)胺反应。
3.权利要求2所述的方法，该方法包括以二甲基亚砜为有机溶剂。
4.权利要求1所述的方法，该方法包括在酸结合剂的存在下进行通式(II)化合物与通式(III)化合物的反应。
5.权利要求4所述的方法，该方法包括以胺或过量的通式化合物为酸结合剂。
6.权利要求1所述的方法，该方法包括在酸性介质中进行水解。
7.权利要求6所述的方法，该方法包括在有机酸或无机酸的存在下进行水解。
8.权利要求1所述的方法，该方法包括在碱性介质中进行水解。
9.权利要求8所述的方法，该方法包括在碱金属氢氧化物、碱土金属氢氧化物或有机碱的存在下进行水解。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU6560/88 | 1988-12-22 | ||
| HU886560A HU203746B (en) | 1988-12-22 | 1988-12-22 | Process for producing quinoline-carboxylic acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1043712A CN1043712A (zh) | 1990-07-11 |
| CN1031190C true CN1031190C (zh) | 1996-03-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN89109448A Expired - Fee Related CN1031190C (zh) | 1988-12-22 | 1989-12-22 | 喹啉羧酸衍生物的制备方法 |
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| Country | Link |
|---|---|
| JP (1) | JP2825641B2 (zh) |
| KR (1) | KR0146335B1 (zh) |
| CN (1) | CN1031190C (zh) |
| AT (1) | AT397385B (zh) |
| AU (1) | AU622256B2 (zh) |
| FR (1) | FR2640974B1 (zh) |
| GB (1) | GB2245562B (zh) |
| HU (1) | HU203746B (zh) |
| IL (1) | IL92821A0 (zh) |
| WO (1) | WO1990006922A1 (zh) |
| YU (1) | YU47215B (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2077490B1 (es) * | 1992-11-18 | 1996-10-16 | Marga Investigacion | Esteres trimetilsililicos y solvatos de quelatos de acidos quinolin-3-carboxilicos. preparacion y aplicacion al proceso de quinolonas. |
| NZ260530A (en) * | 1994-05-16 | 1997-06-24 | Nigel Paul Maynard | Organoborate complexes of divalent metal; use as timber treament agents |
| ES2092963B1 (es) * | 1995-04-12 | 1997-12-16 | Sint Quimica Sa | Procedimiento para la preparacion del acido 1-ciclopropil-6-fluoro-1, 4-dihidro-7-(1s,4s)-5-metil-2,5-diazabiciclo(2.2.1) hept-2-il)-4-oxo-3-quinolincarboxilico y sus sales. |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS59122470A (ja) * | 1982-12-27 | 1984-07-14 | Dai Ichi Seiyaku Co Ltd | キノリン−３−カルボン酸誘導体の製造法 |
| US4550167A (en) * | 1983-05-23 | 1985-10-29 | Ethyl Corporation | Preparation of 1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinoline carboxylic acid |
| JPS6078986A (ja) * | 1983-10-07 | 1985-05-04 | Dai Ichi Seiyaku Co Ltd | オキサジン誘導体の製法 |
| JPS6165882A (ja) * | 1984-09-06 | 1986-04-04 | Hokuriku Seiyaku Co Ltd | １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸エステル誘導体、及びその製造法 |
| JPS6185381A (ja) * | 1984-10-04 | 1986-04-30 | Hokuriku Seiyaku Co Ltd | １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸誘導体の製造法 |
| HU196782B (en) * | 1985-12-09 | 1989-01-30 | Chinoin Gyogyszer Es Vegyeszet | Process for production of quinoline carbonic acid |
| CA1306750C (en) * | 1985-12-09 | 1992-08-25 | Istvan Hermecz | Process for the preparation of quinoline carboxylic acide |
| US4738800A (en) * | 1986-03-26 | 1988-04-19 | Ciba-Geigy Corporation | Process for the preparation of 1,4-diamino-2,3-dicyanoanthraquinones |
| HU198709B (en) * | 1987-04-08 | 1989-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing quinoline-carboxylic acid derivatives |
| JPS6419069A (en) * | 1987-07-14 | 1989-01-23 | Dainippon Pharmaceutical Co | Production of polyhalogenoquinoline derivative |
-
1988
- 1988-12-22 HU HU886560A patent/HU203746B/hu not_active IP Right Cessation
-
1989
- 1989-12-15 KR KR1019900701858A patent/KR0146335B1/ko not_active IP Right Cessation
- 1989-12-15 WO PCT/HU1989/000063 patent/WO1990006922A1/en unknown
- 1989-12-15 AU AU47480/90A patent/AU622256B2/en not_active Ceased
- 1989-12-15 AT AT0902489A patent/AT397385B/de not_active IP Right Cessation
- 1989-12-15 JP JP2500847A patent/JP2825641B2/ja not_active Expired - Lifetime
- 1989-12-15 GB GB9018360A patent/GB2245562B/en not_active Expired - Lifetime
- 1989-12-20 IL IL92821A patent/IL92821A0/xx not_active IP Right Cessation
- 1989-12-22 CN CN89109448A patent/CN1031190C/zh not_active Expired - Fee Related
- 1989-12-22 YU YU243789A patent/YU47215B/sh unknown
- 1989-12-22 FR FR8917102A patent/FR2640974B1/fr not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR0146335B1 (ko) | 1998-08-17 |
| AU622256B2 (en) | 1992-04-02 |
| FR2640974A1 (zh) | 1990-06-29 |
| IL92821A0 (en) | 1990-09-17 |
| AU4748090A (en) | 1990-07-10 |
| ATA902489A (de) | 1993-08-15 |
| GB9018360D0 (en) | 1990-10-24 |
| HUT52086A (en) | 1990-06-28 |
| KR910700245A (ko) | 1991-03-14 |
| GB2245562B (en) | 1992-12-23 |
| JP2825641B2 (ja) | 1998-11-18 |
| AT397385B (de) | 1994-03-25 |
| YU243789A (en) | 1991-02-28 |
| YU47215B (sh) | 1995-01-31 |
| CN1043712A (zh) | 1990-07-11 |
| HU203746B (en) | 1991-09-30 |
| FR2640974B1 (zh) | 1994-02-18 |
| WO1990006922A1 (en) | 1990-06-28 |
| JPH03502803A (ja) | 1991-06-27 |
| GB2245562A (en) | 1992-01-08 |
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