EA023623B1 - Получение защищенных производных (r)- и (s)-n-(3,4-дифтор-2-(2-фтор-4-йодфениламино)-6-метоксифенил)-1-(2,3-дигидроксипропил)циклопропан-1-сульфонамида - Google Patents
Получение защищенных производных (r)- и (s)-n-(3,4-дифтор-2-(2-фтор-4-йодфениламино)-6-метоксифенил)-1-(2,3-дигидроксипропил)циклопропан-1-сульфонамида Download PDFInfo
- Publication number
- EA023623B1 EA023623B1 EA201200175A EA201200175A EA023623B1 EA 023623 B1 EA023623 B1 EA 023623B1 EA 201200175 A EA201200175 A EA 201200175A EA 201200175 A EA201200175 A EA 201200175A EA 023623 B1 EA023623 B1 EA 023623B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- dimethyl
- fluoro
- dioxolan
- difluoro
- dioxolane
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract description 10
- RDSACQWTXKSHJT-NSHDSACASA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2s)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@H](O)CO)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RDSACQWTXKSHJT-NSHDSACASA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- -1 2-fluoro-4-iodophenyl Chemical group 0.000 claims description 171
- 125000006239 protecting group Chemical group 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 35
- 125000003158 alcohol group Chemical group 0.000 claims description 20
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 claims description 17
- 125000004122 cyclic group Chemical group 0.000 claims description 14
- 125000000424 1,2-diol group Chemical group 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 150000000180 1,2-diols Chemical class 0.000 claims description 8
- SIJBDWPVNAYVGY-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OCCO1 SIJBDWPVNAYVGY-UHFFFAOYSA-N 0.000 claims description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 7
- HTWIZMNMTWYQRN-UHFFFAOYSA-N 2-methyl-1,3-dioxolane Chemical compound CC1OCCO1 HTWIZMNMTWYQRN-UHFFFAOYSA-N 0.000 claims description 7
- ZJINNOYGAUCFHL-UHFFFAOYSA-N 2-tert-butyl-1,3-dioxolane Chemical compound CC(C)(C)C1OCCO1 ZJINNOYGAUCFHL-UHFFFAOYSA-N 0.000 claims description 7
- GZGPRZYZKBQPBQ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decane Chemical compound O1CCOC11CCCCC1 GZGPRZYZKBQPBQ-UHFFFAOYSA-N 0.000 claims description 6
- LYINTWKRUWVLBA-UHFFFAOYSA-N 2-phenyl-1,3-dioxolane Chemical compound O1CCOC1C1=CC=CC=C1 LYINTWKRUWVLBA-UHFFFAOYSA-N 0.000 claims description 6
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 5
- 230000003993 interaction Effects 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 150000003871 sulfonates Chemical class 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- BFLWXPJTAKXXKT-UHFFFAOYSA-N 3-methoxybenzene-1,2-diamine Chemical compound COC1=CC=CC(N)=C1N BFLWXPJTAKXXKT-UHFFFAOYSA-N 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 239000000203 mixture Substances 0.000 description 76
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
- 239000000243 solution Substances 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
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- 239000012267 brine Substances 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 239000013058 crude material Substances 0.000 description 19
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
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- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
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- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- CHIZZOFKANZMRQ-UHFFFAOYSA-M sodium;cyclopropanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1CC1 CHIZZOFKANZMRQ-UHFFFAOYSA-M 0.000 description 7
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 6
- QRXQBAGNRUOEEY-UHFFFAOYSA-N 4-iodopent-4-ene-1,2-diol Chemical compound OCC(O)CC(I)=C QRXQBAGNRUOEEY-UHFFFAOYSA-N 0.000 description 6
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 description 6
- NQUFBBVYXNYYDX-UHFFFAOYSA-N cyclopropanethiol Chemical compound SC1CC1 NQUFBBVYXNYYDX-UHFFFAOYSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
- WYNRNIMDJHCRPV-UHFFFAOYSA-N (cyclopropyldisulfanyl)cyclopropane Chemical compound C1CC1SSC1CC1 WYNRNIMDJHCRPV-UHFFFAOYSA-N 0.000 description 4
- MORRHCSCUJQFEK-UHFFFAOYSA-N 1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonyl chloride Chemical compound OCC(O)CC1(S(Cl)(=O)=O)CC1 MORRHCSCUJQFEK-UHFFFAOYSA-N 0.000 description 4
- OGIKZMAHLZCSJJ-UHFFFAOYSA-N 1-(2-fluoro-4-iodophenyl)-3-methoxycyclohexa-3,5-diene-1,2-diamine Chemical compound FC1=C(C=CC(=C1)I)C1(C(C(=CC=C1)OC)N)N OGIKZMAHLZCSJJ-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 3
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- 238000006735 epoxidation reaction Methods 0.000 description 3
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
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- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Chemical group CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical group 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical group CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 1
- VWGWOTXVWXTFMB-UHFFFAOYSA-N butyl cyclopropanesulfonate Chemical compound CCCCOS(=O)(=O)C1CC1 VWGWOTXVWXTFMB-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000005217 methyl ethers Chemical class 0.000 description 1
- XNAGWHHRYVZGCW-UHFFFAOYSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]cyclopropanesulfonamide Chemical compound C1CC1S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F XNAGWHHRYVZGCW-UHFFFAOYSA-N 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 238000004305 normal phase HPLC Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- LCMJZTYHSITRAQ-UHFFFAOYSA-N tert-butyl-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCO[Si](C)(C)C(C)(C)C LCMJZTYHSITRAQ-UHFFFAOYSA-N 0.000 description 1
- YANSSVVGZPNSKD-UHFFFAOYSA-N tert-butyl-dimethyl-(oxiran-2-ylmethoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCC1CO1 YANSSVVGZPNSKD-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/80—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by distillation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/18—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/26—Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22850109P | 2009-07-24 | 2009-07-24 | |
| US22850909P | 2009-07-24 | 2009-07-24 | |
| PCT/EP2010/004222 WO2011009541A1 (en) | 2009-07-24 | 2010-07-10 | Preparation of (r)- and (s)-n-(3, 4-difluoro-2-(2-fluoro-4-iodophenylamino)--6-methoxyphenyl) -1- (2, 3-dihydroxypropyl)cyclopropane-1-sulfonamide and protected derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201200175A1 EA201200175A1 (ru) | 2012-12-28 |
| EA023623B1 true EA023623B1 (ru) | 2016-06-30 |
Family
ID=42830488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201200175A EA023623B1 (ru) | 2009-07-24 | 2010-07-10 | Получение защищенных производных (r)- и (s)-n-(3,4-дифтор-2-(2-фтор-4-йодфениламино)-6-метоксифенил)-1-(2,3-дигидроксипропил)циклопропан-1-сульфонамида |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US8513443B2 (https=) |
| EP (1) | EP2462111B1 (https=) |
| JP (1) | JP5776115B2 (https=) |
| KR (1) | KR101763437B1 (https=) |
| CN (2) | CN103848808B (https=) |
| AR (1) | AR079183A1 (https=) |
| AU (1) | AU2010275780B2 (https=) |
| BR (1) | BR112012001592A2 (https=) |
| CA (2) | CA2990097A1 (https=) |
| CL (1) | CL2012000192A1 (https=) |
| CO (1) | CO6491075A2 (https=) |
| CR (1) | CR20120044A (https=) |
| CU (1) | CU24113B1 (https=) |
| DO (1) | DOP2012000017A (https=) |
| EA (1) | EA023623B1 (https=) |
| EC (1) | ECSP12011621A (https=) |
| GT (1) | GT201200017A (https=) |
| HN (1) | HN2012000142A (https=) |
| IL (1) | IL217312A (https=) |
| IN (1) | IN2012DN00696A (https=) |
| MA (1) | MA33452B1 (https=) |
| MX (2) | MX2012001063A (https=) |
| MY (1) | MY160421A (https=) |
| NZ (1) | NZ597738A (https=) |
| PE (1) | PE20120573A1 (https=) |
| PH (1) | PH12014500158B1 (https=) |
| SG (1) | SG177535A1 (https=) |
| TN (1) | TN2012000027A1 (https=) |
| TW (1) | TWI524890B (https=) |
| UY (1) | UY32800A (https=) |
| WO (1) | WO2011009541A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI524890B (zh) * | 2009-07-24 | 2016-03-11 | 亞德生化公司 | （ｒ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺及（ｓ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺之製備 |
| PH12013502446A1 (en) * | 2011-05-27 | 2014-01-20 | Bayer Ip Gmbh | Chiral synthesis of n-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides |
| JPWO2013094546A1 (ja) * | 2011-12-19 | 2015-04-27 | 住友化学株式会社 | スルホン酸塩の製造方法 |
| EP2848246A1 (en) | 2013-09-13 | 2015-03-18 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007121269A2 (en) * | 2006-04-11 | 2007-10-25 | Ardea Biosciences, Inc. | N-aryl-n'alkyl sulfamides as mek inhibitors |
| US20080058340A1 (en) * | 2005-07-21 | 2008-03-06 | Ardea Biosciences, Inc. | Derivatives of n-(arylamino) sulfonamides as inhibitors of mek |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1912636T1 (sl) * | 2005-07-21 | 2014-08-29 | Ardea Biosciences, Inc. | N-(arilamino)-sulfonamidni inhibitorji MEK |
| MX2008013097A (es) | 2006-04-18 | 2008-10-27 | Ardea Biosciences Inc | Piridona sulfonamidas y piridona sulfamidas como inhibidores de metiletilcetona. |
| UA99731C2 (ru) * | 2007-07-30 | 2012-09-25 | Ардеа Биосайенсис, Инк | Кристаллические полиморфные формы n-(ариламино)сульфонамидов как ингибиторы мэк, композиция (варианты) и применение |
| US8808742B2 (en) * | 2008-04-14 | 2014-08-19 | Ardea Biosciences, Inc. | Compositions and methods for preparing and using same |
| TWI524890B (zh) * | 2009-07-24 | 2016-03-11 | 亞德生化公司 | （ｒ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺及（ｓ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺之製備 |
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- 2010-07-10 CU CUP2012000014A patent/CU24113B1/es active IP Right Grant
- 2010-07-10 EP EP10734043.2A patent/EP2462111B1/en active Active
- 2010-07-10 CA CA2990097A patent/CA2990097A1/en not_active Abandoned
- 2010-07-10 BR BR112012001592A patent/BR112012001592A2/pt not_active Application Discontinuation
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- 2010-07-10 WO PCT/EP2010/004222 patent/WO2011009541A1/en not_active Ceased
- 2010-07-10 AU AU2010275780A patent/AU2010275780B2/en not_active Ceased
- 2010-07-22 UY UY0001032800A patent/UY32800A/es not_active Application Discontinuation
- 2010-07-23 AR ARP100102678A patent/AR079183A1/es unknown
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2012
- 2012-01-01 IL IL217312A patent/IL217312A/en not_active IP Right Cessation
- 2012-01-19 TN TNP2012000027A patent/TN2012000027A1/en unknown
- 2012-01-23 CR CR20120044A patent/CR20120044A/es unknown
- 2012-01-24 CL CL2012000192A patent/CL2012000192A1/es unknown
- 2012-01-24 CO CO12010431A patent/CO6491075A2/es active IP Right Grant
- 2012-01-24 DO DO2012000017A patent/DOP2012000017A/es unknown
- 2012-01-24 MX MX2014000732A patent/MX344965B/es unknown
- 2012-01-24 GT GT201200017A patent/GT201200017A/es unknown
- 2012-01-24 EC EC2012011621A patent/ECSP12011621A/es unknown
- 2012-01-24 HN HN2012000142A patent/HN2012000142A/es unknown
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2013
- 2013-04-23 US US13/868,621 patent/US8884058B2/en not_active Expired - Fee Related
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2014
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- 2014-08-25 US US14/467,424 patent/US9296686B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080058340A1 (en) * | 2005-07-21 | 2008-03-06 | Ardea Biosciences, Inc. | Derivatives of n-(arylamino) sulfonamides as inhibitors of mek |
| WO2007121269A2 (en) * | 2006-04-11 | 2007-10-25 | Ardea Biosciences, Inc. | N-aryl-n'alkyl sulfamides as mek inhibitors |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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