CN103848808B - Mek酶抑制剂的中间体 - Google Patents
Mek酶抑制剂的中间体 Download PDFInfo
- Publication number
- CN103848808B CN103848808B CN201310670649.XA CN201310670649A CN103848808B CN 103848808 B CN103848808 B CN 103848808B CN 201310670649 A CN201310670649 A CN 201310670649A CN 103848808 B CN103848808 B CN 103848808B
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- China
- Prior art keywords
- fluoro
- cyclopropane
- dimethyl
- bis
- base
- 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.)
- Expired - Fee Related
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- 239000002532 enzyme inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- -1 fluoro-4-iodoanilino Chemical group 0.000 abstract description 73
- WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 abstract description 54
- 238000002360 preparation method Methods 0.000 abstract description 17
- 239000002585 base Substances 0.000 description 47
- 238000000034 method Methods 0.000 description 34
- 125000006239 protecting group Chemical group 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 21
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 14
- 125000006241 alcohol protecting group Chemical group 0.000 description 13
- 230000008878 coupling Effects 0.000 description 13
- 238000010168 coupling process Methods 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 11
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- 239000011630 iodine Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical class SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 9
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 8
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 7
- 0 CC1(C)OC(CC(*(N)(O)Cl)=I)C*1 Chemical compound CC1(C)OC(CC(*(N)(O)Cl)=I)C*1 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 235000013325 dietary fiber Nutrition 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000004146 Propane-1,2-diol Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000012069 chiral reagent Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000012434 nucleophilic reagent Substances 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000005694 sulfonylation reaction Methods 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- 125000002769 thiazolinyl group Chemical group 0.000 description 2
- 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
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- FRPCAHHPHLTDDV-ZETCQYMHSA-N CC1(C)O[C@@H](CC(S(Cl)(=O)=O)=C)CO1 Chemical compound CC1(C)O[C@@H](CC(S(Cl)(=O)=O)=C)CO1 FRPCAHHPHLTDDV-ZETCQYMHSA-N 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000006469 Jacobsen epoxidation reaction Methods 0.000 description 1
- MPYCDQUKYGDNPO-UHFFFAOYSA-N NC(C(F)=C1)=CC#CC1I Chemical compound NC(C(F)=C1)=CC#CC1I MPYCDQUKYGDNPO-UHFFFAOYSA-N 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
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- DCTJQEOUKQRZPZ-UHFFFAOYSA-N SS.C1(CC1)C1CC1 Chemical class SS.C1(CC1)C1CC1 DCTJQEOUKQRZPZ-UHFFFAOYSA-N 0.000 description 1
- 238000003457 Shi epoxidation reaction Methods 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- AWCRUOGGUGOOID-UHFFFAOYSA-N [methoxy-[methoxy(phenylmethoxy)methoxy]methoxy]methylbenzene Chemical compound C=1C=CC=CC=1COC(OC)OC(OC)OCC1=CC=CC=C1 AWCRUOGGUGOOID-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000006256 asymmetric dihydroxylation reaction Methods 0.000 description 1
- 230000008901 benefit Effects 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
- 125000001743 benzylic group Chemical group 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
- SFCFVKMVXZETHQ-UHFFFAOYSA-N butyl propane-1-sulfonate Chemical compound CCCCOS(=O)(=O)CCC SFCFVKMVXZETHQ-UHFFFAOYSA-N 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 125000005266 diarylamine group Chemical group 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 compound [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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 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
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- TYZYRCHEVXXLSJ-UHFFFAOYSA-N phenylmethoxymethoxymethoxymethylbenzene Chemical compound C=1C=CC=CC=1COCOCOCC1=CC=CC=C1 TYZYRCHEVXXLSJ-UHFFFAOYSA-N 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 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
- 230000001681 protective effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000005834 sharpless asymmetric dihydroxylation reaction Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- QAZLUNIWYYOJPC-UHFFFAOYSA-M sulfenamide Chemical class [Cl-].COC1=C(C)C=[N+]2C3=NC4=CC=C(OC)C=C4N3SCC2=C1C QAZLUNIWYYOJPC-UHFFFAOYSA-M 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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 | ||
| CN201080031572.6A CN102471246B (zh) | 2009-07-24 | 2010-07-10 | (r)和(s)-n-(3,4-二氟-2-(2-氟-4-碘苯氨基)-6-甲氧基苯基)-1-(2,3-二羟基丙基)环丙烷-1-磺酰胺及它们受保护的衍生物的制备 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080031572.6A Division CN102471246B (zh) | 2009-07-24 | 2010-07-10 | (r)和(s)-n-(3,4-二氟-2-(2-氟-4-碘苯氨基)-6-甲氧基苯基)-1-(2,3-二羟基丙基)环丙烷-1-磺酰胺及它们受保护的衍生物的制备 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103848808A CN103848808A (zh) | 2014-06-11 |
| CN103848808B true CN103848808B (zh) | 2016-02-10 |
Family
ID=42830488
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| CN201080031572.6A Expired - Fee Related CN102471246B (zh) | 2009-07-24 | 2010-07-10 | (r)和(s)-n-(3,4-二氟-2-(2-氟-4-碘苯氨基)-6-甲氧基苯基)-1-(2,3-二羟基丙基)环丙烷-1-磺酰胺及它们受保护的衍生物的制备 |
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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 |
| CN101495118A (zh) * | 2005-07-21 | 2009-07-29 | 阿迪亚生命科学公司 | Mek的n-(芳基氨基)磺酰胺抑制剂 |
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| US8101799B2 (en) * | 2005-07-21 | 2012-01-24 | Ardea Biosciences | Derivatives of N-(arylamino) sulfonamides as inhibitors of 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 |
|---|---|---|---|---|
| CN101495118A (zh) * | 2005-07-21 | 2009-07-29 | 阿迪亚生命科学公司 | Mek的n-(芳基氨基)磺酰胺抑制剂 |
| WO2007121269A2 (en) * | 2006-04-11 | 2007-10-25 | Ardea Biosciences, Inc. | N-aryl-n'alkyl sulfamides as mek inhibitors |
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