ME01466B - Hemijski proces - Google Patents
Hemijski procesInfo
- Publication number
- ME01466B ME01466B MEP-2013-21A MEP2113A ME01466B ME 01466 B ME01466 B ME 01466B ME P2113 A MEP2113 A ME P2113A ME 01466 B ME01466 B ME 01466B
- Authority
- ME
- Montenegro
- Prior art keywords
- formula
- compound
- process according
- salt
- base
- Prior art date
Links
- 238000001311 chemical methods and process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 56
- 238000000034 method Methods 0.000 claims 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 21
- 150000003839 salts Chemical class 0.000 claims 18
- 239000002585 base Substances 0.000 claims 13
- 239000012458 free base Substances 0.000 claims 11
- 239000000203 mixture Substances 0.000 claims 10
- 239000002904 solvent Substances 0.000 claims 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 8
- 238000006243 chemical reaction Methods 0.000 claims 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 5
- 239000012320 chlorinating reagent Substances 0.000 claims 5
- 238000011065 in-situ storage Methods 0.000 claims 5
- 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 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 4
- 125000006239 protecting group Chemical group 0.000 claims 4
- XIHOMGRMQWNHHB-UHFFFAOYSA-N 4-(4-bromo-2-fluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F XIHOMGRMQWNHHB-UHFFFAOYSA-N 0.000 claims 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 239000006227 byproduct Substances 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 3
- 239000008096 xylene Substances 0.000 claims 3
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 claims 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- 230000001476 alcoholic effect Effects 0.000 claims 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 2
- 239000011541 reaction mixture Substances 0.000 claims 2
- 229910052708 sodium Inorganic materials 0.000 claims 2
- 239000011734 sodium Substances 0.000 claims 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 2
- -1 sulfonate ester Chemical class 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical group C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims 2
- 238000005406 washing Methods 0.000 claims 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 claims 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000012280 lithium aluminium hydride Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (28)
1.Proces za proizvodnju jedinjenja sa Formulom VI: gde R1 je zaštitna grupa labilne kiseline iz jedinjenja sa Formulom VII: naznačen time, da pomenuti proces obuhvata: (g) reakciju jedinjenja sa Formulom VII sa prikladnim agensom za hlorovanje u prisutnosti prikladne baze i prikladnog rastvarača, gde je reakcija provodi uz pomoć: (g-1) dodavanja mešavine jedinjenja sa Formulom VII i baze u rastvaraču u mešavinu agensa za hlorovanje u rastvaraču na temperaturi u rasponu od 60 do 90° C tokom perioda od oko 60 min; ili (g-2) dodavanja agensa za hlorovanje u mešavinu jedinjenja sa Formulom VI1 i baze u rastvaraču na ambijentalnoj temperaturi tokom perioda od oko 15 min, a tada uz pomoć grejanja reakcione mešavine tokom perioda od oko 90 min na temperaturi u rasponu od 70 do 90° C i uz mešanje reakcione mešavine na istoj temperaturi od oko 1 h; ili (g-3) dodavanja agensa za hlorovanje u mešavinu jedinjenja sa Formulom VII i baze u rastvaraču na temperaturi u rasponu od 60 do 110° C tokom perioda od oko 15 min, a sa ciljem dobijanja jedinjenja sa Formulom VIII: (h) reakciju jedinjenja sa Formulom VIII sa 4-bromo-2-fluoroanilinom in situ u prisutnosti rastvarača koji se koristi u koraku (g) sa ciljem nastajanja hlorovodonične soli jedinjenja sa Formulom VI; i gde jedinjenje sa Formulom VI. dobiveno u formi hlorovodonične soli, može da se konvertuje u slobodnu bazu ili u formu neke alternativne soli, ako je potrebno.
2. Proces u skladu sa zahtevom 1, naznačen time, da koraci (g) i (h) se oba provode u toluenu.
3. Proces u skladu sa zahtevom 1 ili 2, naznačen time, da agens za hlorovanje, koji se koristi u koraku (g) je fosforni oksihlorid.
4. Proces u skladu sa jednim ili više od zahteva od 1 do 3, naznačen time, da baza, koja se koristi u koraku (g) je izabrana među trietilamina i N,N-diizopropiletilamina.
5. Proces u skladu sa jednim ili više od zahteva od 1 do 4, naznačen time, da dodatno uključuje korak (i) za izolovanje jedinjenja sa Formulom VI.
6. Proces za proizvodnju 7-hidroksi-4-(4-bromo-2-fluoroanilino)-6-metoksikinazolina, jedinjenja sa Formulom IX: iz jedinjenja sa Formulom VII: gde R1 je zaštitna grupa labilne kiseline naznačen time, da pomenuti proces obuhvata korake konvertovanja jedinjenja sa Formulom VII ujedinjenje sa Formulom VI: (j) odstranjivanja R1 sa jedinjenja sa Formulom VI in situ u prisutnosti rastvarača koji se koristi u koracima (g) i (h) sa ciljem nastajanja jedinjenja sa Formulom IX ili njegove soli; i gde jedinjenje sa Formulom IX, dobiveno u formi slobodne baze, može da bude konvertovano u formu soli, a jedinjenja sa Formulom IX, dobiveno u formi soli, može da bude konvertovano u slobodnu bazu ili u formu alternativne soli, ako je potrebno.
7. Proces u skladu sa zahtevom 6, naznačen time, da R1 je benzil, a u koraku (j) ta benzilna grupa se odstranjuje in situ uz pomoć reakcije sa trifluorosirćetnom kiselinom na temperaturi u rasponu od 60 do 80° C.
8. Proces u skladu sa zahtevom 6, naznačen time, da R1 je benzil, a ta benzilna grupa se odstranjuje u prisutnosti trifluorosirćetne kiseline, a jedinjenje sa Formulom IX je konvertovano u trifluorosirćetnu kiselu so uz pomoć dodavanja kalijum hidroksida ili uz pomoć dodavanja natrijum hidroksida i vode.
9. Proces za proizvodnju 7-hidroksi-4-(4-bromo-2-fluoroanilino)-6-metoksikinazolina, jedinjenja sa Formulom IX: iz jedinjenja sa Formulom VII: gde R1 je zaštitna grupa labilne kiseline naznačen time, da pomenuti proces obuhvata korake konvertovanja jedinjenja sa Formulom Vll ujedinjenje sa Formulom VI: uz pomoć izvođenja procesa u skladu sa zahtevom 5; i (k) odstranjivanja R1 iz jedinjenja sa Formulom VI sa ciljem nastajanja jedinjenja sa Formulom IX ili njegove soli; i gde jedinjenje sa Formulom IX, dobiveno u formi slobodne baze, može da bude konvertovano u formu soli, a jedinjenje sa Formulom IX, dobiveno u formi soli, može da bude konvertovano u slobodnu bazu ili u formu neke alternativne soli, ako je potrebno.
10. Proces u skladu sa zahtevom 9, naznačen time, da R1 je benzil, a u koraku (k) ta benzilna grupa se odstranjuje uz pomoć reakcije sa prikladnim agensom za hidrogenovanje.
11. Proces za proizvodnju 7-(l-tert-butoksikarbonil)piperidin-4-ilmetoksi)-4-(4-bromo-2- fluoroanilino)-6-metoksikinazolina, jedinjenja sa Formulom X: iz jedinjenja sa Formulom VII: gde R1 je zaštitna grupa labilne kiseline naznačen time, da pomenuti proces obuhvata korake konvertovanja jedinjenja sa Formulom VII ujedinjenje sa Formulom IX: (I)reakcije jedinjenja sa Formulom IX sa jedinjenjem sa Formulom II: u prisutnosti prikladne baze sa ciljem nastajanja jedinjenja sa Formulom X ili njegove soli; i gde jedinjenje sa Formulom X, dobiveno u formi slobodne baze, može da se konvertuje u formu soli, a jedinjenje sa Formulom X, dobiveno u formi soli, može da se konvertuje u slobodnu bazu ili u formu alternativne soli, ako je potrebno.
12. Proces u skladu sa zahtevom 11, naznačen time, da baza koja se koristi u koraku (1) je izabrana među natrijum karbonata, kalijum karbonata, natrijum hidroksida i kalijum hidroksida.
13. Proces u skladu sa zahtevom 11 ili 12, naznačen time, da dodatno uključuje korak (m) izolovanja jedinjenja sa Formulom X.
14. Proces za proizvodnju 7-(l-te/7-butoksikarbonil)piperidin-4-ilmetoksi)-4-(4-bromo-2- fluoroanilino)-6-metoksikinazolina, jedinjenja sa Formulom X: iz 7-hidroksi-4-(4-bromo-2-fluoroanilino)-6-metoksikinazolina, jedinjenja sa Formulom IX: naznačen time, da pomenuti proces obuhvata: (1) reakciju jedinjenja sa Formulom IX sa jedinjenjem sa Formulom II: u prisutnosti prikladne baze sa ciljem nastajanja jedinjenja sa Formulom X ili njegove soli; i (m) izolovanja jedinjenja sa Formulom X uz pomoć: (m-1) dodavanja vode i dozvoljavanja kristalizovanja jedinjenja sa Formulom X, i sakupljanja jedinjenja sa Formulom X i pranja jedinjenja sa Formulom X sa vodom, a nakon toga sa rastvaračem izabranim od etil acetata, butil acetata i acetonitrila na temperaturi u rasponu od 25 do 55° C; ili (m-2) dodavanja vode i alkohola izabranog od metanola, etanola, izopropanola i n-propanola i dozvoljavanja kristalizovanja jedinjenja sa Formulom X, i sakupljanja jedinjenja sa Formulom X i pranja jedinjenja sa Formulom X sa mešavinom vode i alkohola izabranog od metanola, etanola, izopropanola i n-propanola, a nakon toga sa rastvaračem izabranim među etil acetata, butil acetata i acetonitrila na temperaturi u rasponu od 25 to 55° C; i gde jedinjenje sa Formulom X, dobiveno u fonni slobodne baze. može da se konvertuje u formu soli, a jedinjenje sa Formulom X, dobiveno u formi soli, može da se konvertuje u formu slobodne baze ili u formu neke alternativne soli, ako je potrebno.
15. Proces u skladu sa zahtevom 14, naznačen time, da baza koja se koristi u koraku (1) je izabrana među natrijum karbonata i kalijum karbonata.
16. Proces u skladu sa jednim ili više od zahteva od 11 do 15, naznačen time, da jedinjenje sa Formulom II, koje se koristi u koraku (1), se priprema iz (Cl-C6)alkil-4- piperidinkarboksilatnog jedinjenja sa Formulom III: naznačen time, da pomenuti proces obuhvata: (a)reakciju (Cl-C6)alkil-4-piperidinkarboksilatnog jedinjenja sa Formulom III sa di-/er/-butil dikarbonatom u prisutnosti toluena ili ksilena sa ciljem nastanka prve mešavine koja obuhvata toluen ili ksilen, tert-butanol i jedinjenje sa Formulom IV: (b)značajno odstranjivanje tert-butanola iz prve mešavine; (c)reakciju jedinjenja sa Formulom IV sa prikladnim agensom za redukovanje in situ u prisutnosti toluena ili ksilena sa ciljem nastanka druge mešavine koja obuhvata toluen, nus-produkte redukcije uključujući alkoholne nus-produkte i jedinjenje sa Formulom V: (d)značajno odstranjivanje alkoholnih nus-produkata iz druge mešavine; i (e)reakciju jedinjenja sa Formulom V sa tosilhloridom in situ sa ciljem nastajanja sulfonatnog estera u prisutnosti prikladne baze i toluena sa ciljem nastanka jedinjenja sa Formulom II.
17. Proces u skladu sa zahtevom 16, naznačen time, da (Cl-C6)alkil-4- piperidinkarboksilatno jedinjenje sa Formulom III je etil 4-piperidinkarboksilat.
18. Proces u skladu sa zahtevom 16 ili 17, naznačen time, da u koraku (c) agens za redukovanje je izabran od natrijum bi(2-metoksietoksi)aluminijum hidrida, litijum aluminijum hidrida i diizobutilaluminijum hidrida.
19. Proces u skladu sa zahtevom 18, naznačen time, da u koraku (c) agens za redukovanje je natrijum bi(2-metoksietoksi)aluminijum hidrid.
20. Proces u skladu sa jednim ili više od zahteva od 16 do 19, naznačen time, da u koraku (e) baza je trietilendiamin.
21. Proces u skladu sa jednim ili više od zahteva od 16 do 20, naznačen time, da dodatno uključuje korak (f) za izolovanje jedinjenja sa Formulom II.
22. Proces u skladu sa zahtevom 21, naznačen time, da korak (f) obuhvata kristal izovanje uz pomoć sistema rastvarača sa toluenom i izoheksanom.
23. Proces za proizvodnju 4-(4-bromo-2-fluoroanilino)-6-metoksi-7-(l-metilpiperidin-4- ilmetoksijkinazolina, ZD6474: iz jedinjenja sa Formulom X: naznačen time, da pomenuti proces obuhvata: (n) reakciju jedinjenja sa Formulom X sa mravljom kiselinom i formaldehidom ili sa polimerom formaldehida sa ciljem nastajanja soli mravlje kiseline ZD6474; (o) dodavanje inertnog organskog rastvarača i prikladne baze sa ciljem nastajanja slobodne baze ZD6474; gde ZD6474, dobiven u formi slobodne baze, može da se konvertuje u farmaceutski prihvatljivu so, ako je potrebno.
24. Proces u skladu sa zahtevom 23, naznačen time, da se korak (n) provodi u vodi na temperaturi u rasponu od 70 do 90° C.
25. Proces u skladu sa zahtevom 23 ili zahtevom 24, naznačen time, da je inertni organski rastvarač, koji se koristi u koraku (o), izabran među tetrahidrofurana. butironitrila i metanola.
26. Proces u skladu sa jednim ili više od zahteva od 23 do 25, naznačen time, da baza koja se koristi u koraku (o) je izabrana među natrijum hidroksida i kalijum hidroksida.
27. Proces u skladu sa jednim ili više od zahteva od 23 do 26, naznačen time. da jedinjenje sa Formulom X, koje se koristi u koraku (n), se priprema u skladu sa procesom koji odgovara opisima iz jednog ili više od zahteva od 1 do 16.
28. Proces u skladu sa jednim ili više od zahteva od 23 do 27, naznačen time, da obuhvata dodatno prečišćavanje ZD6474 u mešavini tetrahidrofurana, vode i butil acetata sa ciljem osiguravanja kristalne bezvodne forme.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0519879.1A GB0519879D0 (en) | 2005-09-30 | 2005-09-30 | Chemical process |
| EP06794582A EP1943240B1 (en) | 2005-09-30 | 2006-09-27 | Chemical process |
| PCT/GB2006/003587 WO2007036713A2 (en) | 2005-09-30 | 2006-09-27 | Chemical process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME01466B true ME01466B (me) | 2014-04-20 |
Family
ID=35395001
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2013-51A ME01531B (me) | 2005-09-30 | 2006-09-27 | Hemijski in situ postupak sulfoniranja |
| MEP-2013-21A ME01466B (me) | 2005-09-30 | 2006-09-27 | Hemijski proces |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2013-51A ME01531B (me) | 2005-09-30 | 2006-09-27 | Hemijski in situ postupak sulfoniranja |
Country Status (31)
| Country | Link |
|---|---|
| US (8) | US8163926B2 (me) |
| EP (2) | EP2053048B8 (me) |
| JP (2) | JP5213715B2 (me) |
| KR (1) | KR101307641B1 (me) |
| CN (3) | CN102503933B (me) |
| AR (1) | AR055671A1 (me) |
| AT (2) | ATE481399T1 (me) |
| AU (1) | AU2006296367B2 (me) |
| BR (1) | BRPI0616715A2 (me) |
| CA (2) | CA2745829C (me) |
| CY (2) | CY1110275T1 (me) |
| DE (2) | DE602006010428D1 (me) |
| DK (2) | DK2053048T3 (me) |
| ES (2) | ES2350513T3 (me) |
| GB (1) | GB0519879D0 (me) |
| HR (2) | HRP20100019T1 (me) |
| IL (2) | IL190172A (me) |
| ME (2) | ME01531B (me) |
| MY (2) | MY145540A (me) |
| NO (1) | NO342152B1 (me) |
| NZ (2) | NZ593930A (me) |
| PL (2) | PL1943240T3 (me) |
| PT (2) | PT2053048E (me) |
| RS (2) | RS51263B (me) |
| RU (1) | RU2448102C2 (me) |
| SG (1) | SG165416A1 (me) |
| SI (2) | SI2053048T1 (me) |
| TW (2) | TWI424991B (me) |
| UY (1) | UY29824A1 (me) |
| WO (1) | WO2007036713A2 (me) |
| ZA (1) | ZA200802416B (me) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1474420T3 (da) * | 2002-02-01 | 2012-05-21 | Astrazeneca Ab | Quinazolinforbindelser |
| GB0519879D0 (en) * | 2005-09-30 | 2005-11-09 | Astrazeneca Ab | Chemical process |
| CL2007003158A1 (es) * | 2006-11-02 | 2008-05-16 | Astrazeneca Ab | Procedimiento de preparacion de compuestos derivados de quinazolina o sus sales farmaceuticamente aceptables; compuestos intermediarios; procedimiento de preparacion. |
| ES2547902T3 (es) * | 2011-09-01 | 2015-10-09 | Symrise Ag | Procedimiento para la preparación de derivados de indanona |
| ES2893473T3 (es) * | 2012-08-15 | 2022-02-09 | Glaxo Group Ltd | Proceso químico |
| CN104098544A (zh) * | 2013-04-07 | 2014-10-15 | 浙江九洲药物科技有限公司 | 一种凡德他尼的制备方法 |
| CN106397401B (zh) * | 2016-08-30 | 2018-11-13 | 山东罗欣药业集团股份有限公司 | 一种抗癌药物的晶体化合物及其制备方法 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870083A (en) * | 1987-11-24 | 1989-09-26 | Merrell Dow Pharmaceuticals Inc. | 1,4-Disubstituted-piperidinyl compounds useful as analgesics and muscle relaxants |
| JP2829744B2 (ja) | 1989-05-31 | 1998-12-02 | 川研ファインケミカル株式会社 | ピペリジンカルボン酸類の製造方法 |
| WO1992006086A1 (en) | 1990-10-01 | 1992-04-16 | Janssen Pharmaceutica N.V. | Novel 4-piperidinylcarbonyl derivatives |
| AU658194B2 (en) | 1991-03-28 | 1995-04-06 | Eisai Co. Ltd. | Heterocyclic-cyclic amine derivatives |
| AU658646B2 (en) | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| CA2118117A1 (en) | 1993-02-18 | 1994-08-19 | Shigeki Fujiwara | Adenosine uptake inhibitor |
| AU680004B2 (en) | 1993-05-26 | 1997-07-17 | Syntex (U.S.A.) Inc. | Novel 1-phenylalkanone 5-HT4 receptor ligands |
| DE4326344A1 (de) | 1993-08-05 | 1995-02-09 | Thomae Gmbh Dr K | Carbonamide, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| ATE170174T1 (de) * | 1994-01-13 | 1998-09-15 | Merck Sharp & Dohme | Gem-bissubstituierte azazyclische tachykinin- antagonisten |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| ATE211134T1 (de) | 1996-03-05 | 2002-01-15 | 4-anilinochinazolin derivate | |
| WO1998010767A2 (en) | 1996-09-13 | 1998-03-19 | Sugen, Inc. | Use of quinazoline derivatives for the manufacture of a medicament in the treatment of hyperproliferative skin disorders |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| PL203782B1 (pl) * | 1999-11-05 | 2009-11-30 | Astrazeneca Ab | Pochodne chinazoliny,sposoby ich wytwarzania,ich kompozycje farmaceutyczne oraz ich zastosowania |
| GB0126879D0 (en) | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| AU2002366801B8 (en) | 2001-12-20 | 2009-05-21 | Osi Pharmaceuticals, Inc. | Pyrrolopyrimidine A2b selective antagonist compounds, their synthesis and use |
| DK1474420T3 (da) | 2002-02-01 | 2012-05-21 | Astrazeneca Ab | Quinazolinforbindelser |
| JP4389205B2 (ja) | 2002-02-06 | 2009-12-24 | 宇部興産株式会社 | ４−アミノキナゾリン化合物の製法 |
| GB0218526D0 (en) | 2002-08-09 | 2002-09-18 | Astrazeneca Ab | Combination therapy |
| WO2004014383A1 (en) | 2002-08-09 | 2004-02-19 | Astrazeneca Ab | Combination of zd6474, an inhibitor of the vascular endothelial growth factor receptor, with radiotherapy in the treatment of cancer |
| GB0223380D0 (en) | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| ATE506062T1 (de) | 2003-02-13 | 2011-05-15 | Astrazeneca Ab | Kombinationstherapie von zd6474 mit 5-fu oder/und cpt-11 |
| EP1648465B1 (en) | 2003-07-10 | 2010-08-25 | AstraZeneca AB | Use of the quinazoline derivative zd6474 combined with platinum compounds and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability |
| GB0318423D0 (en) | 2003-08-06 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
| GB0519879D0 (en) * | 2005-09-30 | 2005-11-09 | Astrazeneca Ab | Chemical process |
-
2005
- 2005-09-30 GB GBGB0519879.1A patent/GB0519879D0/en not_active Ceased
-
2006
- 2006-09-27 RU RU2008116573/04A patent/RU2448102C2/ru not_active IP Right Cessation
- 2006-09-27 PL PL06794582T patent/PL1943240T3/pl unknown
- 2006-09-27 US US12/088,680 patent/US8163926B2/en active Active
- 2006-09-27 DE DE602006010428T patent/DE602006010428D1/de active Active
- 2006-09-27 AU AU2006296367A patent/AU2006296367B2/en not_active Ceased
- 2006-09-27 ES ES09152654T patent/ES2350513T3/es active Active
- 2006-09-27 DE DE602006017004T patent/DE602006017004D1/de active Active
- 2006-09-27 ME MEP-2013-51A patent/ME01531B/me unknown
- 2006-09-27 CN CN201110159628.2A patent/CN102503933B/zh active Active
- 2006-09-27 ES ES06794582T patent/ES2335435T3/es active Active
- 2006-09-27 NZ NZ593930A patent/NZ593930A/xx not_active IP Right Cessation
- 2006-09-27 MY MYPI20080855A patent/MY145540A/en unknown
- 2006-09-27 MY MYPI2011003076A patent/MY149834A/en unknown
- 2006-09-27 NZ NZ566566A patent/NZ566566A/en not_active IP Right Cessation
- 2006-09-27 JP JP2008532864A patent/JP5213715B2/ja not_active Expired - Fee Related
- 2006-09-27 EP EP09152654A patent/EP2053048B8/en active Active
- 2006-09-27 PL PL09152654T patent/PL2053048T3/pl unknown
- 2006-09-27 CN CN201110159729.XA patent/CN102503898B/zh active Active
- 2006-09-27 DK DK09152654.1T patent/DK2053048T3/da active
- 2006-09-27 CN CN200680036468XA patent/CN101277948B/zh active Active
- 2006-09-27 WO PCT/GB2006/003587 patent/WO2007036713A2/en not_active Ceased
- 2006-09-27 SI SI200630816T patent/SI2053048T1/sl unknown
- 2006-09-27 CA CA2745829A patent/CA2745829C/en not_active Expired - Fee Related
- 2006-09-27 RS RSP-2010/0037A patent/RS51263B/sr unknown
- 2006-09-27 SG SG201006940-9A patent/SG165416A1/en unknown
- 2006-09-27 CA CA2624045A patent/CA2624045C/en not_active Expired - Fee Related
- 2006-09-27 KR KR1020087009317A patent/KR101307641B1/ko not_active Expired - Fee Related
- 2006-09-27 PT PT09152654T patent/PT2053048E/pt unknown
- 2006-09-27 RS RSP-2010/0520A patent/RS51515B/sr unknown
- 2006-09-27 AT AT09152654T patent/ATE481399T1/de active
- 2006-09-27 BR BRPI0616715-2A patent/BRPI0616715A2/pt not_active IP Right Cessation
- 2006-09-27 DK DK06794582.4T patent/DK1943240T3/da active
- 2006-09-27 EP EP06794582A patent/EP1943240B1/en active Active
- 2006-09-27 PT PT06794582T patent/PT1943240E/pt unknown
- 2006-09-27 HR HR20100019T patent/HRP20100019T1/hr unknown
- 2006-09-27 ME MEP-2013-21A patent/ME01466B/me unknown
- 2006-09-27 SI SI200630524T patent/SI1943240T1/sl unknown
- 2006-09-27 AT AT06794582T patent/ATE448218T1/de active
- 2006-09-29 UY UY29824A patent/UY29824A1/es unknown
- 2006-09-29 AR ARP060104320A patent/AR055671A1/es not_active Application Discontinuation
- 2006-09-29 TW TW099102690A patent/TWI424991B/zh not_active IP Right Cessation
- 2006-09-29 TW TW095136340A patent/TWI328580B/zh not_active IP Right Cessation
-
2008
- 2008-03-11 NO NO20081267A patent/NO342152B1/no not_active IP Right Cessation
- 2008-03-13 IL IL190172A patent/IL190172A/en not_active IP Right Cessation
- 2008-03-14 ZA ZA200802416A patent/ZA200802416B/xx unknown
-
2010
- 2010-01-25 CY CY20101100076T patent/CY1110275T1/el unknown
- 2010-11-12 CY CY20101101019T patent/CY1110887T1/el unknown
- 2010-11-16 HR HR20100620T patent/HRP20100620T1/hr unknown
-
2011
- 2011-12-07 US US13/314,034 patent/US8865899B2/en active Active
-
2012
- 2012-11-28 JP JP2012259782A patent/JP5654546B2/ja not_active Expired - Fee Related
-
2013
- 2013-07-21 IL IL227574A patent/IL227574A/en not_active IP Right Cessation
-
2014
- 2014-09-09 US US14/481,302 patent/US20140378684A1/en not_active Abandoned
-
2015
- 2015-07-22 US US14/805,816 patent/US9815816B2/en active Active
-
2017
- 2017-10-27 US US15/796,615 patent/US10344015B2/en active Active
-
2019
- 2019-05-08 US US16/406,246 patent/US20190263782A1/en not_active Abandoned
-
2020
- 2020-11-02 US US17/086,666 patent/US20220033377A1/en not_active Abandoned
-
2023
- 2023-03-07 US US18/118,549 patent/US20240150317A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2699438C (en) | Method for preparing disubstituted piperidine and intermediates | |
| EP3057942B1 (en) | 1,4-cyclohexylamine derivatives and processes for the preparation thereof | |
| AU2012319291B2 (en) | Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride and intermediates used therein | |
| CN101528700A (zh) | 用于制备伊马替尼的方法及其中间体 | |
| EP2044021B1 (en) | Process for preparing remifentanil, intermediates thereof, use of said intermediates and processes for their preparation | |
| ME01466B (me) | Hemijski proces | |
| JP6461011B2 (ja) | １−（４−（４−（３，４−ジクロロ−２−フルオロフェニルアミノ）−７−メトキシキナゾリン−６−イルオキシ）ピペリジン−１−イル）プロパ−２−エン−１−オンの製造方法 | |
| JP4560293B2 (ja) | 医薬上有効な化合物（グラニセトロン）の製造方法 | |
| CN106866501A (zh) | 一种盐酸左布比卡因的制备方法 | |
| JP2004131465A5 (me) | ||
| US8802851B2 (en) | Process for preparing vilazodone hydrochloride | |
| JP2011236157A (ja) | 光学活性ニペコチン酸誘導体の製造方法 | |
| US7202360B2 (en) | Method for preparing risperidone | |
| KR102068754B1 (ko) | 의약품 합성용 중간체 화합물의 제조 방법 | |
| US8030491B2 (en) | Process and intermediate for preparation of donepezil | |
| WO2001021592A1 (en) | Processes for the preparation of 4(5)-amino-5(4)-carboxamidoimidazoles and intermediates thereof | |
| CN104892491B (zh) | 一种合成帕罗西汀手性中间体的方法 | |
| WO2013084241A1 (en) | Compounds as inhibitors of renin | |
| US10844014B2 (en) | Intermediates for the preparation of remifentanil hydrochloride | |
| JP4790901B2 (ja) | ４−アミノ−５−シアノイミダゾール誘導体及びその中間体の製造方法 | |
| US8093384B2 (en) | Processes for the preparation of alfuzosin | |
| KR20200088570A (ko) | 피마살탄 및 그의 제조 중간체의 제조방법 | |
| JP4871445B2 (ja) | アデニン誘導体の製造方法 | |
| TW200846337A (en) | A production method for the qunolon-carboxylic acid derivative | |
| US7547789B2 (en) | Process for the preparation of N-(4-piperidinyl)-N-ethyl-phenylacetamides from N-Boc-4-oxopiperidine |