ZA200702511B - Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide - Google Patents
Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide Download PDFInfo
- Publication number
- ZA200702511B ZA200702511B ZA200702511A ZA200702511A ZA200702511B ZA 200702511 B ZA200702511 B ZA 200702511B ZA 200702511 A ZA200702511 A ZA 200702511A ZA 200702511 A ZA200702511 A ZA 200702511A ZA 200702511 B ZA200702511 B ZA 200702511B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- compound
- reacting
- give
- chloro
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 31
- 238000000034 method Methods 0.000 title claims description 15
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 237
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 49
- 239000002904 solvent Substances 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 45
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 40
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 40
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 claims description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 36
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 238000004519 manufacturing process Methods 0.000 claims description 22
- NBJZEUQTGLSUOB-UHFFFAOYSA-N 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(N=C=O)=CC=C1Cl NBJZEUQTGLSUOB-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 238000002425 crystallisation Methods 0.000 claims description 14
- 230000008025 crystallization Effects 0.000 claims description 13
- 239000012948 isocyanate Substances 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- 150000002513 isocyanates Chemical class 0.000 claims description 11
- -1 4-chloro-3- trifluoromethylphenyl Chemical group 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 239000002798 polar solvent Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 150000005323 carbonate salts Chemical class 0.000 claims description 5
- 150000004682 monohydrates Chemical class 0.000 claims 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 1
- 235000013350 formula milk Nutrition 0.000 description 195
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000002955 isolation Methods 0.000 description 8
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 8
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 229960000443 hydrochloric acid Drugs 0.000 description 6
- 235000011167 hydrochloric acid Nutrition 0.000 description 6
- 239000003444 phase transfer catalyst Substances 0.000 description 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000001376 precipitating effect Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 238000009740 moulding (composite fabrication) Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000007938 chlorocyclic compounds Chemical class 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 231100001010 corrosive Toxicity 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- HXXAUIXTYRHFNO-UHFFFAOYSA-N n-methylpyridine-2-carboxamide Chemical compound CNC(=O)C1=CC=CC=N1 HXXAUIXTYRHFNO-UHFFFAOYSA-N 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- INCUNNRDSKWZKZ-UHFFFAOYSA-N pyridine-2-carboxylic acid;hydrobromide Chemical compound Br.OC(=O)C1=CC=CC=N1 INCUNNRDSKWZKZ-UHFFFAOYSA-N 0.000 description 1
- 102000009929 raf Kinases Human genes 0.000 description 1
- 108010077182 raf Kinases Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP04023131 | 2004-09-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200702511B true ZA200702511B (en) | 2008-07-30 |
Family
ID=35457568
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200702511A ZA200702511B (en) | 2004-09-29 | 2007-03-27 | Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide |
Country Status (35)
Country | Link |
---|---|
US (1) | US8124782B2 (fr) |
EP (1) | EP1797037B1 (fr) |
JP (2) | JP2008514657A (fr) |
KR (1) | KR101263032B1 (fr) |
CN (1) | CN101052619B (fr) |
AR (1) | AR053973A1 (fr) |
AU (1) | AU2005289099B2 (fr) |
BR (1) | BRPI0515944B1 (fr) |
CA (1) | CA2581835C (fr) |
CU (1) | CU23754B7 (fr) |
CY (1) | CY1116126T1 (fr) |
DK (1) | DK1797037T3 (fr) |
DO (1) | DOP2005000183A (fr) |
EC (1) | ECSP077357A (fr) |
ES (1) | ES2532377T3 (fr) |
GT (1) | GT200500269A (fr) |
HK (1) | HK1113484A1 (fr) |
HN (1) | HN2005000768A (fr) |
HR (1) | HRP20150295T1 (fr) |
IL (1) | IL182046A0 (fr) |
MA (1) | MA28883B1 (fr) |
MY (1) | MY149873A (fr) |
NO (1) | NO339647B1 (fr) |
NZ (1) | NZ554119A (fr) |
PE (5) | PE20091585A1 (fr) |
PL (1) | PL1797037T3 (fr) |
PT (1) | PT1797037E (fr) |
SG (1) | SG155997A1 (fr) |
SI (1) | SI1797037T1 (fr) |
SV (1) | SV2006002243A (fr) |
TW (1) | TWI382973B (fr) |
UA (1) | UA90691C2 (fr) |
UY (1) | UY29143A1 (fr) |
WO (1) | WO2006034796A1 (fr) |
ZA (1) | ZA200702511B (fr) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2359244C (fr) | 1999-01-13 | 2013-10-08 | Bayer Corporation | Diphenyle urees a substitution .omega.-carboxy aryle en tant qu'inhibiteurs de la kinase p38 |
US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
JP4636486B2 (ja) | 2002-02-11 | 2011-02-23 | バイエル、ファーマシューテイカルズ、コーポレイション | 脈管形成阻害活性を有するアリール尿素 |
ATE366108T1 (de) | 2003-05-20 | 2007-07-15 | Bayer Pharmaceuticals Corp | Diaryl-harnstoffe für durch pdgfr vermittelte krankheiten |
PL1663978T3 (pl) | 2003-07-23 | 2008-04-30 | Bayer Healthcare Llc | Fluoropodstawiony omega-karboksyarylodifenylomocznik do leczenia i profilaktyki chorób i stanów |
EP1797038B1 (fr) * | 2004-09-29 | 2012-06-13 | Bayer Pharma Aktiengesellschaft | Forme thermodynamiquement stable de tosylate de bay 43-9006 |
NZ554119A (en) | 2004-09-29 | 2010-07-30 | Bayer Schering Pharma Ag | Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide |
AU2006222365B2 (en) | 2005-03-07 | 2011-07-14 | Bayer Healthcare Llc | Pharmaceutical composition comprising an omega- carboxyaryl substituted diphenyl urea for the treatment of cancer |
AR062927A1 (es) * | 2006-10-11 | 2008-12-17 | Bayer Healthcare Ag | 4- [4-( [ [ 4- cloro-3-( trifluorometil) fenil) carbamoil] amino] -3- fluorofenoxi) -n- metilpiridin-2- carboxamida monohidratada |
WO2008058644A1 (fr) * | 2006-11-14 | 2008-05-22 | Bayer Schering Pharma Aktiengesellschaft | Polymorphe ii de 4-[4-({[4-chloro-3-(trifluorométhyl)phényl]carbamoyl}amino)-3-fluorophénoxy]-n-méthylpyridine-2-carboxamide |
AU2008299703C1 (en) * | 2007-09-10 | 2013-09-05 | Cipla Limited | Process for the preparation of a RAF kinase inhibitor and intermediates for use in the process |
WO2009054004A2 (fr) * | 2007-10-22 | 2009-04-30 | Natco Pharma Limited | Nouveau procédé pour la préparation du sorafénib |
US8217061B2 (en) | 2008-01-17 | 2012-07-10 | Sicor Inc. | Polymorphs of sorafenib tosylate and sorafenib hemi-tosylate, and processes for preparation thereof |
EP2142507A1 (fr) * | 2008-03-06 | 2010-01-13 | Sicor, Inc. | Procédé de préparation du sorafénib et ses sels |
CN103254126A (zh) * | 2008-09-19 | 2013-08-21 | 苏州泽璟生物制药有限公司 | 氘代的ω-二苯基脲及衍生物以及包含该化合物的药物组合物 |
AU2010299484A1 (en) | 2009-09-24 | 2012-05-03 | Ranbaxy Laboratories Limited | Polymorphs of sorafenib acid addition salts |
CA2775229C (fr) | 2009-09-24 | 2014-07-29 | Ranbaxy Laboratories Limited | Procede de preparation de tosylate de sorafenib |
EP2499116A1 (fr) | 2009-11-12 | 2012-09-19 | Ranbaxy Laboratories Limited | Sel d'ethylsulfonate de sorafenib et son procede de preparation |
WO2011076711A2 (fr) | 2009-12-23 | 2011-06-30 | Ratiopharm Gmbh | Polymorphes de 4-[4-[[4-chloro-3-(trifluorométhyl)phényl]carbamoylamino]phénoxy]-n-méthylpyridine-2-carboxamide |
US8618305B2 (en) | 2010-01-29 | 2013-12-31 | Ranbaxy Laboratories Limited | Sorafenib dimethyl sulphoxide solvate |
CN102190616B (zh) * | 2010-03-18 | 2015-07-29 | 苏州泽璟生物制药有限公司 | 一种氘代的ω-二苯基脲的合成及生产的方法和工艺 |
AR081060A1 (es) | 2010-04-15 | 2012-06-06 | Bayer Schering Pharma Ag | Procedimiento para preparar 4-{4-[({[4-cloro-3-(trifluorometil)fenil]amino}carbonil)amino]-3-fluorofenoxi}-n-metilpiridin-2-carboxamida |
CN102617458A (zh) * | 2010-05-18 | 2012-08-01 | 张南 | 抗癌用化合物的制备方法 |
WO2012012404A1 (fr) | 2010-07-19 | 2012-01-26 | Bayer Healthcare Llc | Associations médicamenteuses contenant une oméga-carboxyaryl diphénylurée fluorosubstituée utilisées pour le traitement et la prévention de maladies et d'affections |
KR20130099117A (ko) | 2010-10-01 | 2013-09-05 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 치환된 n-(2-아릴아미노)아릴 설폰아미드 함유 배합물 |
WO2012071425A1 (fr) | 2010-11-22 | 2012-05-31 | Teva Pharmaceutical Industries Ltd. | Formes à l'état solide de bésylate de sorafénib et procédés de préparation |
EP2559431A1 (fr) | 2011-08-17 | 2013-02-20 | Ratiopharm GmbH | Composition pharmaceutique comportant du 4-[4-[[4-Chloro-3-(trifluoromethyl)phényl]carbamoylamino]phénoxy]-N-méthyl-pyridine-2-carboxamide |
CN103664771B (zh) * | 2012-09-19 | 2016-03-30 | 齐鲁制药有限公司 | 索拉非尼的晶型a及其制备方法 |
WO2014118807A1 (fr) * | 2013-02-04 | 2014-08-07 | Intas Pharmaceuticals Limited | Nouveau procédé de préparation de tosylate de sorafénib de forme iii |
CN104710354A (zh) * | 2013-12-13 | 2015-06-17 | 江苏豪森药业股份有限公司 | 高纯度索拉非尼的制备方法 |
CN104761492A (zh) * | 2014-01-03 | 2015-07-08 | 正大天晴药业集团股份有限公司 | 对甲苯磺酸索拉非尼的晶型及其制备方法 |
CN104177292A (zh) * | 2014-08-08 | 2014-12-03 | 亿腾药业(泰州)有限公司 | 一种工业化生产甲苯磺酸索拉非尼多晶型ⅰ的方法 |
CN105439947A (zh) * | 2014-12-01 | 2016-03-30 | 石药集团中奇制药技术(石家庄)有限公司 | 一种甲苯磺酸索拉非尼新晶型及其制备方法 |
EP3109236B1 (fr) | 2015-06-23 | 2017-08-09 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Procédé évolutif pour la préparation de solvate d'éthanol tosylate de sorafénibe et tosylate de sorafénibe forme iii |
CN105181844A (zh) * | 2015-09-11 | 2015-12-23 | 江苏嘉逸医药有限公司 | 一种高效液相色谱法测定甲苯磺酸索拉非尼含量和有关物质的方法 |
CN105585523A (zh) * | 2015-12-29 | 2016-05-18 | 上海北卡医药技术有限公司 | 一种对甲苯磺酸索拉非尼的新晶型及其制备方法和用途 |
CN107840823B (zh) * | 2016-09-20 | 2021-08-17 | 意大利合成制造有限公司 | 用于制备甲苯磺酸索拉非尼乙醇溶剂化物和iii型甲苯磺酸索拉非尼的可变规模的方法 |
CN107915676A (zh) * | 2017-10-26 | 2018-04-17 | 魏海霞 | 索拉非尼的制备方法 |
CN109796400B (zh) * | 2017-11-16 | 2022-07-29 | 四川科伦药物研究院有限公司 | 一种甲苯磺酸索拉菲尼晶型及其制备方法 |
CN113773249A (zh) * | 2020-06-10 | 2021-12-10 | 杭州中美华东制药有限公司 | 索拉非尼游离碱晶型Form X及其制备方法 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
LU86960A1 (fr) * | 1987-07-31 | 1989-03-08 | Oreal | Procede de preparation de piperidino-6 diamino-2,4 pyrimidine oxyde-3 et composes nouveaux |
JPH02934A (ja) * | 1988-05-27 | 1990-01-05 | Konica Corp | 非線形光学材料 |
JP2971291B2 (ja) * | 1993-06-02 | 1999-11-02 | 田辺製薬株式会社 | 光学活性2−アミノ酪酸の製法 |
JP3866323B2 (ja) * | 1996-03-27 | 2007-01-10 | ポーラ化成工業株式会社 | 新規n−ベンジルベンズアミド誘導体 |
JPH09316069A (ja) * | 1996-03-28 | 1997-12-09 | Ajinomoto Co Inc | 新規キサントン誘導体 |
US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
WO2000042012A1 (fr) | 1999-01-13 | 2000-07-20 | Bayer Corporation | DIPHENYLUREES A SUBSTITUANTS φ-CARBOXYARYLES, INHIBITRICES DE KINASE RAF |
BRPI0007487B8 (pt) * | 1999-01-13 | 2021-05-25 | Bayer Healthcare Llc | difenil-uréias substituídas com w-carbóxi-arilas como inibidores de raf cinase |
GB2367816A (en) * | 2000-10-09 | 2002-04-17 | Bayer Ag | Urea- and thiourea-containing derivatives of beta-amino acids |
ATE345130T1 (de) * | 2001-12-03 | 2006-12-15 | Bayer Pharmaceuticals Corp | Arylharnstoff-verbindungen in kombination mit anderen zytostatisch oder zytotoxisch wirksamen stoffen zur behandlungen menschlicher krebserkrankungen |
US20030207872A1 (en) * | 2002-01-11 | 2003-11-06 | Bayer Corporation | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
DE10203086A1 (de) * | 2002-01-28 | 2003-07-31 | Bayer Ag | 5-Ring Heterozyklen |
JP4636486B2 (ja) * | 2002-02-11 | 2011-02-23 | バイエル、ファーマシューテイカルズ、コーポレイション | 脈管形成阻害活性を有するアリール尿素 |
EP1554289B1 (fr) * | 2002-08-13 | 2011-03-09 | Sandoz Ag | Intermediaire de cefdinir |
ATE374199T1 (de) * | 2002-10-21 | 2007-10-15 | Kirin Brewery | N-ä2-chlor-4-((6,7-dimethoxy-4- chinolyl)oxy)phenylü-n'-(5-methyl-3- isoxazolyl)harnstoffsalzin kristalliner form |
ATE366108T1 (de) * | 2003-05-20 | 2007-07-15 | Bayer Pharmaceuticals Corp | Diaryl-harnstoffe für durch pdgfr vermittelte krankheiten |
NZ554119A (en) | 2004-09-29 | 2010-07-30 | Bayer Schering Pharma Ag | Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide |
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