AU2010275780B2 - 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 - Google Patents
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 Download PDFInfo
- Publication number
- AU2010275780B2 AU2010275780B2 AU2010275780A AU2010275780A AU2010275780B2 AU 2010275780 B2 AU2010275780 B2 AU 2010275780B2 AU 2010275780 A AU2010275780 A AU 2010275780A AU 2010275780 A AU2010275780 A AU 2010275780A AU 2010275780 B2 AU2010275780 B2 AU 2010275780B2
- Authority
- AU
- Australia
- Prior art keywords
- cyclopropane
- dimethyl
- difluoro
- fluoro
- dioxolan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 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 claims abstract description 22
- 238000002360 preparation method Methods 0.000 title abstract description 20
- RDSACQWTXKSHJT-LLVKDONJSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2r)-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-LLVKDONJSA-N 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 29
- 125000006241 alcohol protecting group Chemical group 0.000 claims description 25
- -1 cyclic 1,2-diol Chemical class 0.000 claims description 23
- 150000000180 1,2-diols Chemical group 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- HZMCKCFNDFZVCM-UHFFFAOYSA-N 3,4-difluoro-2-n-(2-fluoro-4-iodophenyl)-6-methoxybenzene-1,2-diamine Chemical compound COC1=CC(F)=C(F)C(NC=2C(=CC(I)=CC=2)F)=C1N HZMCKCFNDFZVCM-UHFFFAOYSA-N 0.000 claims description 5
- 239000012038 nucleophile Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 82
- 239000000243 solution Substances 0.000 description 71
- 239000000203 mixture Substances 0.000 description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 239000011734 sodium Substances 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000013058 crude material Substances 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012267 brine Substances 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 230000008878 coupling Effects 0.000 description 12
- 238000010168 coupling process Methods 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 12
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 12
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- YAYIUFDUYUYPJC-UHFFFAOYSA-N 9-iodo-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2I YAYIUFDUYUYPJC-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- XZKWFWOCXKFYCF-SSDOTTSWSA-N 1-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonyl chloride Chemical compound O1C(C)(C)OC[C@H]1CC1(S(Cl)(=O)=O)CC1 XZKWFWOCXKFYCF-SSDOTTSWSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- MGMMNQCHTQKQQX-FJXQXJEOSA-M sodium;1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonate Chemical compound [Na+].O1C(C)(C)OC[C@@H]1CC1(S([O-])(=O)=O)CC1 MGMMNQCHTQKQQX-FJXQXJEOSA-M 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- XZKWFWOCXKFYCF-ZETCQYMHSA-N 1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonyl chloride Chemical compound O1C(C)(C)OC[C@@H]1CC1(S(Cl)(=O)=O)CC1 XZKWFWOCXKFYCF-ZETCQYMHSA-N 0.000 description 7
- RCQNHFFSUFMNMO-UHFFFAOYSA-N 3,4-difluoro-1-n-(2-fluoro-4-iodophenyl)-6-methoxybenzene-1,2-diamine Chemical compound COC1=CC(F)=C(F)C(N)=C1NC1=CC=C(I)C=C1F RCQNHFFSUFMNMO-UHFFFAOYSA-N 0.000 description 7
- QRXQBAGNRUOEEY-UHFFFAOYSA-N 4-iodopent-4-ene-1,2-diol Chemical compound OCC(O)CC(I)=C QRXQBAGNRUOEEY-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- QRXQBAGNRUOEEY-RXMQYKEDSA-N (2r)-4-iodopent-4-ene-1,2-diol Chemical compound OC[C@H](O)CC(I)=C QRXQBAGNRUOEEY-RXMQYKEDSA-N 0.000 description 6
- LRJSRCLNTLAFOR-KBPBESRZSA-N (4s)-4-[[1-[[1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropyl]disulfanyl]cyclopropyl]methyl]-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OC[C@@H]1CC1(SSC2(C[C@@H]3OC(C)(C)OC3)CC2)CC1 LRJSRCLNTLAFOR-KBPBESRZSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 238000005888 cyclopropanation reaction Methods 0.000 description 6
- 150000002009 diols Chemical class 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- RHSQCLAGWOZJOH-CYBMUJFWSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@H]1OC(C)(C)OC1)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RHSQCLAGWOZJOH-CYBMUJFWSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000006103 sulfonylation Effects 0.000 description 6
- 238000005694 sulfonylation reaction Methods 0.000 description 6
- KQNMBZJILAHXPM-SNVBAGLBSA-N (2r)-1-[tert-butyl(dimethyl)silyl]oxypent-4-yn-2-ol Chemical compound CC(C)(C)[Si](C)(C)OC[C@H](O)CC#C KQNMBZJILAHXPM-SNVBAGLBSA-N 0.000 description 5
- KQNMBZJILAHXPM-JTQLQIEISA-N (2s)-1-[tert-butyl(dimethyl)silyl]oxypent-4-yn-2-ol Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H](O)CC#C KQNMBZJILAHXPM-JTQLQIEISA-N 0.000 description 5
- XOOIQJCVRKUDIR-SSDOTTSWSA-N (4r)-4-(2-iodoprop-2-enyl)-2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OC[C@@H](CC(I)=C)O1 XOOIQJCVRKUDIR-SSDOTTSWSA-N 0.000 description 5
- LRJSRCLNTLAFOR-ZIAGYGMSSA-N (4r)-4-[[1-[[1-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropyl]disulfanyl]cyclopropyl]methyl]-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OC[C@H]1CC1(SSC2(C[C@H]3OC(C)(C)OC3)CC2)CC1 LRJSRCLNTLAFOR-ZIAGYGMSSA-N 0.000 description 5
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 5
- FRPCAHHPHLTDDV-ZETCQYMHSA-N 3-[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]prop-1-ene-2-sulfonyl chloride Chemical compound CC1(C)OC[C@H](CC(=C)S(Cl)(=O)=O)O1 FRPCAHHPHLTDDV-ZETCQYMHSA-N 0.000 description 5
- FYZDPIIMSZAKGP-UHFFFAOYSA-N 9-bromo-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2Br FYZDPIIMSZAKGP-UHFFFAOYSA-N 0.000 description 5
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- RRLVXOZCFUODSW-CYBMUJFWSA-N (2r)-1-[tert-butyl(dimethyl)silyl]oxy-5-trimethylsilylpent-4-yn-2-ol Chemical compound CC(C)(C)[Si](C)(C)OC[C@H](O)CC#C[Si](C)(C)C RRLVXOZCFUODSW-CYBMUJFWSA-N 0.000 description 4
- SLIBESZPANWTRG-RXMQYKEDSA-N (2r)-4-bromopent-4-ene-1,2-diol Chemical compound OC[C@H](O)CC(Br)=C SLIBESZPANWTRG-RXMQYKEDSA-N 0.000 description 4
- QRXQBAGNRUOEEY-YFKPBYRVSA-N (2s)-4-iodopent-4-ene-1,2-diol Chemical compound OC[C@@H](O)CC(I)=C QRXQBAGNRUOEEY-YFKPBYRVSA-N 0.000 description 4
- XOOIQJCVRKUDIR-ZETCQYMHSA-N (4s)-4-(2-iodoprop-2-enyl)-2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OC[C@H](CC(I)=C)O1 XOOIQJCVRKUDIR-ZETCQYMHSA-N 0.000 description 4
- WYNRNIMDJHCRPV-UHFFFAOYSA-N (cyclopropyldisulfanyl)cyclopropane Chemical compound C1CC1SSC1CC1 WYNRNIMDJHCRPV-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- MGMMNQCHTQKQQX-OGFXRTJISA-M sodium;1-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonate Chemical compound [Na+].O1C(C)(C)OC[C@H]1CC1(S([O-])(=O)=O)CC1 MGMMNQCHTQKQQX-OGFXRTJISA-M 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FDGOVLGJKSWDDP-RXMQYKEDSA-N (2r)-3-(1-iodocyclopropyl)propane-1,2-diol Chemical compound OC[C@H](O)CC1(I)CC1 FDGOVLGJKSWDDP-RXMQYKEDSA-N 0.000 description 3
- RRLVXOZCFUODSW-ZDUSSCGKSA-N (2s)-1-[tert-butyl(dimethyl)silyl]oxy-5-trimethylsilylpent-4-yn-2-ol Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H](O)CC#C[Si](C)(C)C RRLVXOZCFUODSW-ZDUSSCGKSA-N 0.000 description 3
- QXHGDAZVUPAABN-SSDOTTSWSA-N (4r)-4-[(1-iodocyclopropyl)methyl]-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OC[C@H]1CC1(I)CC1 QXHGDAZVUPAABN-SSDOTTSWSA-N 0.000 description 3
- 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 3
- WZQDCSPGEMTDTM-SSDOTTSWSA-N 1-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-thiol Chemical compound O1C(C)(C)OC[C@H]1CC1(S)CC1 WZQDCSPGEMTDTM-SSDOTTSWSA-N 0.000 description 3
- WZQDCSPGEMTDTM-ZETCQYMHSA-N 1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-thiol Chemical compound O1C(C)(C)OC[C@@H]1CC1(S)CC1 WZQDCSPGEMTDTM-ZETCQYMHSA-N 0.000 description 3
- SIJBDWPVNAYVGY-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OCCO1 SIJBDWPVNAYVGY-UHFFFAOYSA-N 0.000 description 3
- FRPCAHHPHLTDDV-SSDOTTSWSA-N 3-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]prop-1-ene-2-sulfonyl chloride Chemical compound CC1(C)OC[C@@H](CC(=C)S(Cl)(=O)=O)O1 FRPCAHHPHLTDDV-SSDOTTSWSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000012069 chiral reagent Substances 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
- 238000006735 epoxidation reaction Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- RDSACQWTXKSHJT-UHFFFAOYSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide Chemical compound C1CC1(CC(O)CO)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RDSACQWTXKSHJT-UHFFFAOYSA-N 0.000 description 3
- GAOTVJNSYXCSHT-UHFFFAOYSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-prop-2-enylcyclopropane-1-sulfonamide Chemical compound C1CC1(CC=C)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F GAOTVJNSYXCSHT-UHFFFAOYSA-N 0.000 description 3
- OIAHNQABECBIMF-CYBMUJFWSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-3-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]prop-1-ene-2-sulfonamide Chemical compound C([C@H]1OC(C)(C)OC1)C(=C)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F OIAHNQABECBIMF-CYBMUJFWSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- FFRBQTHSBRPONV-OAHLLOKOSA-N tert-butyl-[(2r)-1-[tert-butyl(dimethyl)silyl]oxy-3-(1-iodocyclopropyl)propan-2-yl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC[C@H](O[Si](C)(C)C(C)(C)C)CC1(I)CC1 FFRBQTHSBRPONV-OAHLLOKOSA-N 0.000 description 3
- HRSLWOAEWVTKDV-OAHLLOKOSA-N tert-butyl-[(2r)-2-[tert-butyl(dimethyl)silyl]oxy-4-iodopent-4-enoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H](CC(I)=C)O[Si](C)(C)C(C)(C)C HRSLWOAEWVTKDV-OAHLLOKOSA-N 0.000 description 3
- FDGOVLGJKSWDDP-YFKPBYRVSA-N (2s)-3-(1-iodocyclopropyl)propane-1,2-diol Chemical compound OC[C@@H](O)CC1(I)CC1 FDGOVLGJKSWDDP-YFKPBYRVSA-N 0.000 description 2
- SLIBESZPANWTRG-YFKPBYRVSA-N (2s)-4-bromopent-4-ene-1,2-diol Chemical compound OC[C@@H](O)CC(Br)=C SLIBESZPANWTRG-YFKPBYRVSA-N 0.000 description 2
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- FDGOVLGJKSWDDP-UHFFFAOYSA-N 3-(1-iodocyclopropyl)propane-1,2-diol Chemical class OCC(O)CC1(I)CC1 FDGOVLGJKSWDDP-UHFFFAOYSA-N 0.000 description 2
- LRJSRCLNTLAFOR-UHFFFAOYSA-N 4-[[1-[[1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]cyclopropyl]disulfanyl]cyclopropyl]methyl]-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OCC1CC1(SSC2(CC3OC(C)(C)OC3)CC2)CC1 LRJSRCLNTLAFOR-UHFFFAOYSA-N 0.000 description 2
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- 101710191566 Probable endopolygalacturonase I Proteins 0.000 description 2
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- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
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- 238000005658 halogenation reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000026045 iodination Effects 0.000 description 2
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
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- 239000000463 material Substances 0.000 description 2
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- 238000006722 reduction reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
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- 229940124530 sulfonamide Drugs 0.000 description 2
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- 229910052717 sulfur Inorganic materials 0.000 description 2
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- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000006469 Jacobsen epoxidation reaction Methods 0.000 description 1
- 238000006763 Lemieux-Johnson oxidation reaction Methods 0.000 description 1
- WTRFBMJKMINKIM-UHFFFAOYSA-N OCC(O)CC1([Li])CC1 Chemical compound OCC(O)CC1([Li])CC1 WTRFBMJKMINKIM-UHFFFAOYSA-N 0.000 description 1
- 102100027069 Odontogenic ameloblast-associated protein Human genes 0.000 description 1
- 101710091533 Odontogenic ameloblast-associated protein Proteins 0.000 description 1
- 101150045055 PCSK2 gene Proteins 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 240000002426 Persea americana var. drymifolia Species 0.000 description 1
- 229910005948 SO2Cl Inorganic materials 0.000 description 1
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 1
- 238000003457 Shi epoxidation reaction Methods 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 241001155518 Stephos Species 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
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000006256 asymmetric dihydroxylation reaction Methods 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
- VWGWOTXVWXTFMB-UHFFFAOYSA-N butyl cyclopropanesulfonate Chemical compound CCCCOS(=O)(=O)C1CC1 VWGWOTXVWXTFMB-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 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
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
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- 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
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
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- 150000005217 methyl ethers Chemical class 0.000 description 1
- RHSQCLAGWOZJOH-ZDUSSCGKSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@@H]1OC(C)(C)OC1)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RHSQCLAGWOZJOH-ZDUSSCGKSA-N 0.000 description 1
- OIAHNQABECBIMF-ZDUSSCGKSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-3-[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]prop-1-ene-2-sulfonamide Chemical compound C([C@@H]1OC(C)(C)OC1)C(=C)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F OIAHNQABECBIMF-ZDUSSCGKSA-N 0.000 description 1
- IIOJJZKXHLUULQ-UHFFFAOYSA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide Chemical compound C=1C=C(F)C(F)=C(NC=2C(=CC(I)=CC=2)F)C=1NS(=O)(=O)C1(CC(O)CO)CC1 IIOJJZKXHLUULQ-UHFFFAOYSA-N 0.000 description 1
- 238000004305 normal phase HPLC Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- YANSSVVGZPNSKD-MRVPVSSYSA-N tert-butyl-dimethyl-[[(2r)-oxiran-2-yl]methoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OC[C@H]1CO1 YANSSVVGZPNSKD-MRVPVSSYSA-N 0.000 description 1
- YANSSVVGZPNSKD-QMMMGPOBSA-N tert-butyl-dimethyl-[[(2s)-oxiran-2-yl]methoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H]1CO1 YANSSVVGZPNSKD-QMMMGPOBSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical group CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
- 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
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
-
- 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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22850109P | 2009-07-24 | 2009-07-24 | |
| US22850909P | 2009-07-24 | 2009-07-24 | |
| US61/228,501 | 2009-07-24 | ||
| US61/228,509 | 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 |
|---|---|
| AU2010275780A1 AU2010275780A1 (en) | 2012-02-02 |
| AU2010275780B2 true AU2010275780B2 (en) | 2015-10-22 |
Family
ID=42830488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010275780A Ceased AU2010275780B2 (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 |
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=) |
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| 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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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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