HRP20110184T1 - Postupak priprave 5-(haloacetil)-8-(supstituirani oksi)-(1h)-kinolin-2-ona - Google Patents
Postupak priprave 5-(haloacetil)-8-(supstituirani oksi)-(1h)-kinolin-2-ona Download PDFInfo
- Publication number
- HRP20110184T1 HRP20110184T1 HR20110184T HRP20110184T HRP20110184T1 HR P20110184 T1 HRP20110184 T1 HR P20110184T1 HR 20110184 T HR20110184 T HR 20110184T HR P20110184 T HRP20110184 T HR P20110184T HR P20110184 T1 HRP20110184 T1 HR P20110184T1
- Authority
- HR
- Croatia
- Prior art keywords
- quinolin
- hydroxy
- acetyl
- substituted oxy
- solvent
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract 15
- 238000002360 preparation method Methods 0.000 title claims abstract 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract 13
- 239000002904 solvent Substances 0.000 claims abstract 13
- PJVZAXRWCFBQFH-UHFFFAOYSA-N 5-acetyl-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(=O)C PJVZAXRWCFBQFH-UHFFFAOYSA-N 0.000 claims abstract 9
- 239000002841 Lewis acid Substances 0.000 claims abstract 8
- 150000007517 lewis acids Chemical class 0.000 claims abstract 8
- ZXZKYYHTWHJHFT-UHFFFAOYSA-N quinoline-2,8-diol Chemical compound C1=CC(=O)NC2=C1C=CC=C2O ZXZKYYHTWHJHFT-UHFFFAOYSA-N 0.000 claims abstract 8
- UTMRKCQYCLEKDL-UHFFFAOYSA-N (2-oxo-1h-quinolin-8-yl) acetate Chemical compound C1=CC(=O)NC2=C1C=CC=C2OC(=O)C UTMRKCQYCLEKDL-UHFFFAOYSA-N 0.000 claims abstract 7
- -1 5-acetyl-8-substituted oxy- (1H) -quinolin-2-one Chemical class 0.000 claims abstract 6
- 150000001875 compounds Chemical class 0.000 claims abstract 5
- 230000002140 halogenating effect Effects 0.000 claims abstract 5
- 125000006239 protecting group Chemical group 0.000 claims abstract 5
- 150000003839 salts Chemical class 0.000 claims 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 150000001450 anions Chemical class 0.000 claims 3
- 239000002585 base Substances 0.000 claims 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 238000011065 in-situ storage Methods 0.000 claims 2
- 150000008040 ionic compounds Chemical class 0.000 claims 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims 2
- 239000011541 reaction mixture Substances 0.000 claims 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- CRRUGYDDEMGVDY-UHFFFAOYSA-N 1-bromoethylbenzene Chemical compound CC(Br)C1=CC=CC=C1 CRRUGYDDEMGVDY-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- AUFKEUKWVZCLQD-UHFFFAOYSA-N 5-(2-chloroacetyl)-8-phenylmethoxy-1h-quinolin-2-one Chemical group C1=2NC(=O)C=CC=2C(C(=O)CCl)=CC=C1OCC1=CC=CC=C1 AUFKEUKWVZCLQD-UHFFFAOYSA-N 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 1
- 229910015900 BF3 Inorganic materials 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 claims 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 claims 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims 1
- 239000012346 acetyl chloride Substances 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 150000008064 anhydrides Chemical group 0.000 claims 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims 1
- 229940073608 benzyl chloride Drugs 0.000 claims 1
- YOUGRGFIHBUKRS-UHFFFAOYSA-N benzyl(trimethyl)azanium Chemical group C[N+](C)(C)CC1=CC=CC=C1 YOUGRGFIHBUKRS-UHFFFAOYSA-N 0.000 claims 1
- PPDJNZTUDFPAHX-UHFFFAOYSA-N benzyltrimethylammonium dichloroiodate Chemical compound Cl[I-]Cl.C[N+](C)(C)CC1=CC=CC=C1 PPDJNZTUDFPAHX-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 claims 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002460 imidazoles Chemical class 0.000 claims 1
- QZZUEBNBZAPZLX-QFIPXVFZSA-N indacaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 239000002608 ionic liquid Substances 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 150000004714 phosphonium salts Chemical class 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 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
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pulmonology (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Quinoline Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Abstract
Postupak priprave 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-ona, naznačen time, da obuhvaćaa) reagiranjei) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom i Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on; iliii) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom da se stvori 8-acetoksi-(1H)-kinolin-2-on, i obrađivanje, na samom mjestu, 8-acetoksi-(1H)-kinolin-2-ona s Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on; b) reagiranje 5-acetil-8-hidroksi-(1H)-kinolin-2-ona pripravljenog u koraku (a) sa spojem formule RL u prisutnosti baze i otapala, da se stvori 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-on, pri čemu R je zaštitna skupina a L je izlazna skupina; ic) reagiranje 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-ona s halogenirajućim agensom u prisutnosti otapala da se stvori 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-on. Patent sadrži još 13 patentnih zahtjeva.
Claims (14)
1. Postupak priprave 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-ona, naznačen time, da obuhvaća
a) reagiranje
i) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom i Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on; ili
ii) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom da se stvori 8-acetoksi-(1H)-kinolin-2-on, i obrađivanje, na samom mjestu, 8-acetoksi-(1H)-kinolin-2-ona s Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on;
b) reagiranje 5-acetil-8-hidroksi-(1H)-kinolin-2-ona pripravljenog u koraku (a) sa spojem formule RL u prisutnosti baze i otapala, da se stvori 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-on, pri čemu R je zaštitna skupina a L je izlazna skupina; i
c) reagiranje 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-ona s halogenirajućim agensom u prisutnosti otapala da se stvori 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-on.
2. Postupak prema zahtjevu 1, naznačen time, da je acilatni agens prisutan u količini od 1 molarnog ekvivalenta do 1,5 molarnih ekvivalenata, bazirano na molarnim ekvivalentima od 8-hidroksi-(1H)-kinolin-2-ona.
3. Postupak prema zahtjevu 2, naznačen time, da je acilatni agens anhidrid ili acetil klorid.
4. Postupak prema bilo kojem zahtjevu 1 do 3, naznačen time, da je Lewisova kiselina prisutna u količini od 3 molarna ekvivalenta do 5 molarnih ekvivalenata, bazirano na molarnim ekvivalentima od 8-hidroksi-(1H)-kinolin-2-ona ili na molarnim ekvivalentima od 8-acetoksi-(1H)-kinolin-2-ona.
5. Postupak prema zahtjevu 4, naznačen time, da je Lewisova kiselina borov trifluorid, aluminijev klorid ili titanijev tetraklorid.
6. Postupak prema bilo kojem zahtjevu 1 do 5, naznačen time, da je korak (a) proveden u prisutnosti jednog ionskog spoja, pri čemu je ionski spoj alkalijski halid odabran iz skupine koja se sastoji od natrijevog klorida, natrijevog bromida, litijevog klorida i litijevog bromida, ili je to ionska tekućina odabrana iz skupine koja se sastoji od soli imidazola, soli pirida, soli amonijaka, soli fosfonija i soli sulfonija.
7. Postupak prema bilo kojem zahtjevu 1 do 6, naznačen time, da je spoj formule RL odabran iz skupine koja se sastoji od α-metilbenzil bromida, metil klorida, benzil klorida i benzil bromida.
8. Postupak prema bilo kojem zahtjevu 1 do 7, naznačen time, da 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-on je 5-acetil-8-benziloksi-(1H)-kinolin-2-on.
9. Postupak prema bilo kojem zahtjevu 1 do 8, naznačen time, da je halogenirajući agens odabran iz skupine koja se sastoji od natrij bromata i hidrobromične kiseline, broma, N-bromosukcinimida, N-klorosukcinimida, joda, klora, sulfuril klorida, benziltrimetilamonijdikloro-jodata, bakrenog klorida, piridinijevog tribromida, tetraalkilamonijevog tribromida, jodinovog klorida, klorovodične kiseline i oksidacijskog agensa, te od njihovih kombinacija.
10. Postupak prema zahtjevu 9, naznačen time, da je halogenizirajući agens benziltrimetilamonijdiklorojodat.
11. Postupak prema bilo kojem zahtjevu 1 do 10, naznačen time, da 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-on je 5-(α-kloroacetil)-8-benziloksi-(1H)-kinolin-2-on.
12. Postupak prema bilo kojem zahtjevu 1 do 11, naznačen time, da je u koraku (a) otapalo odabrano iz skupine koja se sastoji od metilenklorida, 1,2-etilen diklorida, klorobenzena, o-dikloro-benzena, alifatskog C6-C12-ugljikovodika i njihovih kombinacija; u koraku (b) otapalo je odabrano iz skupine koja se sastoji od acetona, metil izobutil ketona, tetrahidrofurana, diizopropil etera, 2-metoksietil etera, dietilen etera, metilen klorida, vode i njihovih kombinacija; a u koraku (c) otapalo je odabrano iz skupine koja se sastoji od octene kiseline, trifluorooctene kiseline, propionske kiseline, etil acetata, izopropil acetata, butil acetata, toluena, benzena, tetrahidrofurana, diizopropil etera, 2-metoksietil etera, dietilen etera, metilen klorida i njihovih kombinacija.
13. Postupak prema bilo kojem zahtjevu 1 do 12, naznačen time, da u koraku (a) je temperatura od 0°C do 160°C; u koraku (b) temperatura je od 20°C do 90°C; a u koraku (c) temperatura je od 10°C do 160°C.
14. Postupak priprave soli od 5-[(R)-2-(5,6-dietil-indan-2-ilamino)-1-hidroksi-etil]-8-hidroksi-(1H)-kinolinon-2-ona, naznačen time, da obuhvaća:
(a) reagiranje
(i) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom i Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on; ili
(ii) 8-hidroksi-(1H)-kinolin-2-ona s acilatnim agensom da se stvori 8-acetoksi-(1H)-kinolin-2-on, i obrađivanje, na samom mjestu, 8-acetoksi-(1H)-kinolin-2-ona s Lewisovom kiselinom da se stvori 5-acetil-8-hidroksi-(1H)-kinolin-2-on;
(b) reagiranje 5-acetil-8-hidroksi-(1H)-kinolin-2-ona pripravljenog u koraku (i) sa spojem formule RL u prisutnosti baze i otapala da se stvori 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-on, pri čemu R je zaštitna skupina, a L je izlazna skupina;
(c) reagiranje 5-acetil-8-supstituirani oksi-(1H)-kinolin-2-ona sa halogenirajućim agensom u prisutnosti otapala da se stvori 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-on;
(d) reagiranje 5-(α-haloacetil)-8-supstituirani oksi-(1H)-kinolin-2-ona s redukcijskim sredstvom u prisutnosti kiralnog katalizatora da se stvori 8-(supstituirani oksi)-5-((R)-2-halo-1-hidroksi-etil)-(1H)-kinolin-2-on;
(e) obrađivanje 8-(supstituirani oksi)-5-((R)-2-halo-1-hidroksi-etil)-(1H)-kinolin-2-ona s bazom u prisutnosti otapala da se stvori 8-(supstituirani oksi)-5-(R)-oksiranil-(1H)-kinolin-2-on;
(f) reagiranje 8-supstituirani oksi-5-(R)-oksiranil-(1H)-kinolin-2-ona koji ima formulu (I)
[image]
s 2-amino-(5-6-dietil)-indanom da se stvori reakcijska smjesa koja sadrži spojeve s formulama (II), (III) i (IV)
[image]
[image]
gdje R je zaštitna skupina;
(g) obrađivanje reakcijske smjese pripravljene u koraku (f) s kiselinom u prisutnosti otapala da se stvori odgovarajuća sol;
(h) izoliranje i kristalizacija soli koja ima formulu (V)
[image]
gdje R je zaštitna skupina a A- je anion;
(i) uklanjanje zaštitne skupine iz soli koja ima formulu (V) u prisutnosti otapala da se dobije sol koja ima formulu (VI):
[image]
gdje A- je anion; i
(j) obrađivanje soli formule (VI) s kiselinom u prisutnosti otapala da se stvori sol od 5-[(R)-2-(5,6-dietil-indan-2-ilamino)-1-hidroksi-etil]-8-hidroksi-(1H)-kinolin-2-ona koja ima formulu (VII)
[image]
gdje X- je anion.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45972403P | 2003-04-02 | 2003-04-02 | |
| PCT/EP2004/003479 WO2004087668A1 (en) | 2003-04-02 | 2004-04-01 | A process for the preparation of 5-(haloacetyl)-8-(substituted oxy)-(1h)-quinolin-2-ones |
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| Publication Number | Publication Date |
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| HRP20110184T1 true HRP20110184T1 (hr) | 2011-04-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| HR20110184T HRP20110184T1 (hr) | 2003-04-02 | 2011-03-14 | Postupak priprave 5-(haloacetil)-8-(supstituirani oksi)-(1h)-kinolin-2-ona |
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| US (1) | US7605267B2 (hr) |
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| KR (1) | KR101073740B1 (hr) |
| CN (1) | CN1774423A (hr) |
| AR (2) | AR043825A1 (hr) |
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| BR (1) | BRPI0409154B1 (hr) |
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| CO (1) | CO5700779A2 (hr) |
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| DE (1) | DE602004030553D1 (hr) |
| DK (1) | DK1613599T3 (hr) |
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| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| GB0413960D0 (en) * | 2004-06-22 | 2004-07-28 | Novartis Ag | Organic compounds |
| EP2044025B1 (en) | 2006-06-30 | 2012-10-03 | Novartis AG | Quinolinone derivatives and their pharmaceutical compositions |
| WO2013132514A2 (en) * | 2012-03-09 | 2013-09-12 | Rao Davuluri Ramamohan | A novel process for the preparation of (r)-5-[2-[(5, 6-diethyl-2, 3-dihydro-1h-inden-2-yl) amino]-1-hydroxyethyl]-8-hydroxy quinolin-2(1h)-one |
| CN102633717B (zh) * | 2012-03-30 | 2013-11-20 | 西南大学 | N-乙酰-喹啉-2(1h)酮类化合物及其制备方法和应用 |
| CN104379566B (zh) * | 2012-07-11 | 2016-08-24 | 上海威智医药科技有限公司 | 茚达特罗中间体及茚达特罗的合成方法 |
| CZ306252B6 (cs) | 2013-03-15 | 2016-10-26 | Zentiva, K.S. | Způsob přípravy 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-(1H)-chinolin-2-onu (indacaterolu) |
| WO2015104718A2 (en) | 2014-01-09 | 2015-07-16 | Davuluri, Ramamohan Rao | A novel process for preparation of indacaterol or its pharmaceutically acceptable salts |
| CN105693603B (zh) * | 2014-11-24 | 2019-11-29 | 上海医药工业研究院 | 改良的马来酸茚达特罗制备工艺 |
| CN107531636B (zh) * | 2015-04-09 | 2022-11-25 | 正大天晴药业集团股份有限公司 | 茚达特罗或其盐的制备方法 |
| CN107868045A (zh) * | 2016-09-28 | 2018-04-03 | 四川海思科制药有限公司 | 一种茚达特罗中间体的制备方法 |
| CN108264483A (zh) * | 2016-12-31 | 2018-07-10 | 天津金耀集团有限公司 | 一种马来酸茚达特罗的制备方法 |
| CN109721534B (zh) * | 2018-09-25 | 2022-05-20 | 四川海思科制药有限公司 | 一种马来酸茚达特罗中间体及其制备方法和用途 |
| CN114751857A (zh) * | 2022-04-29 | 2022-07-15 | 梯尔希（南京）药物研发有限公司 | 一种茚达特罗杂质的制备方法 |
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| JPS539228B2 (hr) * | 1974-01-31 | 1978-04-04 | ||
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| JPS5896022A (ja) * | 1981-11-30 | 1983-06-07 | Otsuka Pharmaceut Co Ltd | 強心剤 |
| ES519384A0 (es) * | 1983-01-28 | 1984-03-16 | Espanola Farma Therapeut | Procedimiento para la obtencion de un compuesto derivado de la 2-quinolinona. |
| ES8605239A1 (es) | 1985-12-04 | 1986-03-16 | Astur Pharma | Un procedimiento para la preparacion de quinolonas sustitui-das |
| GB9405019D0 (en) * | 1994-03-15 | 1994-04-27 | Smithkline Beecham Plc | Novel compounds |
| GB9913083D0 (en) * | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
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| WO2003042160A1 (en) * | 2001-11-13 | 2003-05-22 | Theravance, Inc. | Aryl aniline beta-2 adrenergic receptor agonists |
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