KR101057239B1 - 뉴클레오사이드 리보푸라노실 피리미딘의 제조 - Google Patents
뉴클레오사이드 리보푸라노실 피리미딘의 제조 Download PDFInfo
- Publication number
- KR101057239B1 KR101057239B1 KR1020097008991A KR20097008991A KR101057239B1 KR 101057239 B1 KR101057239 B1 KR 101057239B1 KR 1020097008991 A KR1020097008991 A KR 1020097008991A KR 20097008991 A KR20097008991 A KR 20097008991A KR 101057239 B1 KR101057239 B1 KR 101057239B1
- Authority
- KR
- South Korea
- Prior art keywords
- aryl
- methyl
- formula
- fluoro
- tetrahydrofuran
- 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.)
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- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 title description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title 1
- 239000002777 nucleoside Substances 0.000 title 1
- 150000003833 nucleoside derivatives Chemical class 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 18
- -1 4-benzoylamino-2-oxo-2H-pyrimidin-1-yl Chemical group 0.000 claims description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 150000002596 lactones Chemical class 0.000 claims description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical group ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 239000012320 chlorinating reagent Substances 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- GYGMOLHWGMLEGA-ORZBULNSSA-N ethyl (e)-3-[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-methylprop-2-enoate Chemical compound CCOC(=O)C(\C)=C\[C@H]1COC(C)(C)O1 GYGMOLHWGMLEGA-ORZBULNSSA-N 0.000 claims description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- BHCHXRCKXIVVCN-XLDPMVHQSA-N ethyl (2s,3r)-3-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,3-dihydroxy-2-methylpropanoate Chemical group CCOC(=O)[C@@](C)(O)[C@H](O)[C@H]1COC(C)(C)O1 BHCHXRCKXIVVCN-XLDPMVHQSA-N 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 3
- GZFKHXHYNNEXBB-KCRUCZTKSA-N (2s,3r)-3-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,3-dihydroxy-2-methylpropanoic acid Chemical compound OC(=O)[C@](O)(C)[C@H](O)[C@H]1COC(C)(C)O1 GZFKHXHYNNEXBB-KCRUCZTKSA-N 0.000 claims description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 2
- JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 claims description 2
- 238000000354 decomposition reaction Methods 0.000 claims description 2
- 230000000593 degrading effect Effects 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- 239000005708 Sodium hypochlorite Substances 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 claims 1
- 229910001626 barium chloride Inorganic materials 0.000 claims 1
- OWNFYVWAEKMUNO-UHFFFAOYSA-N bis(2-methoxyethoxy)-(2,2,2-trifluoroethoxy)alumane;sodium Chemical group [Na].COCCO[Al](OCC(F)(F)F)OCCOC OWNFYVWAEKMUNO-UHFFFAOYSA-N 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 4
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- 239000002002 slurry Substances 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- 229910019093 NaOCl Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- VNCJYMKHJWVTPK-ZMIZWQJLSA-N (3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one Chemical compound C[C@@]1(F)[C@H](O)[C@@H](CO)OC1=O VNCJYMKHJWVTPK-ZMIZWQJLSA-N 0.000 description 2
- NYPIRLYMDJMKGW-UHFFFAOYSA-N 4-amino-1-[3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound CC1(F)C(O)C(CO)OC1N1C(=O)N=C(N)C=C1 NYPIRLYMDJMKGW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- MXEQSUUFNWPUJH-UHFFFAOYSA-N [5-(4-benzamido-2-oxopyrimidin-1-yl)-3-benzoyloxy-4-fluoro-4-methyloxolan-2-yl]methyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1OC(N2C(N=C(NC(=O)C=3C=CC=CC=3)C=C2)=O)C(C)(F)C1OC(=O)C1=CC=CC=C1 MXEQSUUFNWPUJH-UHFFFAOYSA-N 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 2
- XBDUZBHKKUFFRH-UHFFFAOYSA-N n-(2-oxo-1h-pyrimidin-6-yl)benzamide Chemical compound OC1=NC=CC(NC(=O)C=2C=CC=CC=2)=N1 XBDUZBHKKUFFRH-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- ODYBCPSCYHAGHA-ZYUZMQFOSA-N (1s,2s)-1,2-bis[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]ethane-1,2-diol Chemical compound O1C(C)(C)OC[C@@H]1[C@@H](O)[C@H](O)[C@@H]1OC(C)(C)OC1 ODYBCPSCYHAGHA-ZYUZMQFOSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- QAGMBTAACMQRSS-MTULOOOASA-N [(2r,3s)-3,5-diacetyloxyoxolan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1OC(OC(C)=O)C[C@@H]1OC(C)=O QAGMBTAACMQRSS-MTULOOOASA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002431 foraging effect Effects 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000000457 gamma-lactone group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85096206P | 2006-10-10 | 2006-10-10 | |
| US60/850,962 | 2006-10-10 | ||
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Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| ES2624353T3 (es) | 2002-11-15 | 2017-07-13 | Idenix Pharmaceuticals Llc | 2'-Metil nucleósidos en combinación con interferón y mutación de Flaviviridae |
| EP4032897B1 (en) | 2003-05-30 | 2025-01-29 | Gilead Pharmasset LLC | Modified fluorinated nucleoside analogues |
| WO2006031725A2 (en) * | 2004-09-14 | 2006-03-23 | Pharmasset, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| CN101057259B (zh) | 2004-11-16 | 2010-11-03 | 汤姆森许可贸易公司 | 基于预计算的变换系数的胶片颗粒仿真方法 |
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| MX2007005651A (es) | 2004-11-17 | 2007-06-05 | Thomson Licensing | Metodo de simulacion de grano de pelicula exacto de bits con base en coeficientes transformados pre-computados. |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| US10715834B2 (en) | 2007-05-10 | 2020-07-14 | Interdigital Vc Holdings, Inc. | Film grain simulation based on pre-computed transform coefficients |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| SG172359A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Nucleoside phosphoramidates |
| US8551973B2 (en) | 2008-12-23 | 2013-10-08 | Gilead Pharmasset Llc | Nucleoside analogs |
| NZ593647A (en) * | 2008-12-23 | 2013-08-30 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| TW201136945A (en) | 2010-03-31 | 2011-11-01 | Pharmasset Inc | Purine nucleoside phosphoramidate |
| JP2013527145A (ja) | 2010-03-31 | 2013-06-27 | ギリード・ファーマセット・エルエルシー | リン含有活性化剤の立体選択的合成 |
| JP5716500B2 (ja) | 2010-06-03 | 2015-05-13 | セントラル硝子株式会社 | （２Ｒ）−２−フルオロ−２−Ｃ−メチル−Ｄ−リボノ−γ−ラクトン類前駆体の製造方法 |
| PT3042910T (pt) | 2010-11-30 | 2019-04-16 | Gilead Pharmasset Llc | 2'-espiro-nucleósidos para utilização na terapia da hepatite c |
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| WO2013039920A1 (en) | 2011-09-12 | 2013-03-21 | Idenix Pharmaceuticals, Inc. | Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections |
| CA2840242C (en) | 2011-09-16 | 2019-03-26 | Gilead Sciences, Inc. | Methods for treating hcv |
| WO2013056046A1 (en) | 2011-10-14 | 2013-04-18 | Idenix Pharmaceuticals, Inc. | Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections |
| PT107894A (pt) | 2011-10-21 | 2014-10-31 | Abbvie Inc | Métodos para o tratamento de hcv compreendendo pelo menos dois agentes antivirais de actuação directa, ribavirina, mas não interferão. |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| GB2515942A (en) | 2011-10-21 | 2015-01-07 | Abbvie Inc | Combination treatment (e.g. with ABT-072 or ABT-333) of DAAs for use in treating HCV |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| EP2852605B1 (en) | 2012-05-22 | 2018-01-31 | Idenix Pharmaceuticals LLC | 3',5'-cyclic phosphate prodrugs for hcv infection |
| BR112014029115A8 (pt) | 2012-05-22 | 2018-04-03 | Idenix Pharmaceuticals Inc | Composto, composição farmacêutica, e, uso de um composto ou composição |
| EP2852604B1 (en) | 2012-05-22 | 2017-04-12 | Idenix Pharmaceuticals LLC | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
| MX2014014323A (es) | 2012-05-25 | 2015-02-12 | Janssen R & D Ireland | Nucleosidos de espirooxetano de uracilo. |
| HK1207384A1 (en) * | 2012-05-29 | 2016-01-29 | F. Hoffmann-La Roche Ag | Process for the preparation of 2-deoxy-2-fluoro-2-methyl-d-ribofuranosyl nucleoside compounds |
| CN103450148B (zh) * | 2012-06-04 | 2018-06-12 | 浙江九洲药业股份有限公司 | 一种五元环硫酸酯化合物的合成方法 |
| WO2014052638A1 (en) | 2012-09-27 | 2014-04-03 | Idenix Pharmaceuticals, Inc. | Esters and malonates of sate prodrugs |
| CN104936970A (zh) | 2012-10-08 | 2015-09-23 | 埃迪尼克斯医药公司 | 用于hcv感染的2′-氯核苷类似物 |
| CN103724301A (zh) | 2012-10-10 | 2014-04-16 | 上海特化医药科技有限公司 | (2r)-2-脱氧-2,2-二取代-1,4-核糖内酯及其制备方法和用途 |
| US10723754B2 (en) | 2012-10-22 | 2020-07-28 | Idenix Pharmaceuticals Llc | 2′,4′-bridged nucleosides for HCV infection |
| WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| CN103012386B (zh) * | 2012-12-26 | 2015-04-01 | 浙江普洛得邦制药有限公司 | 一种五元环状硫酸酯的制备方法 |
| KR20200060782A (ko) | 2013-01-31 | 2020-06-01 | 길리애드 파마셋 엘엘씨 | 두 항바이러스 화합물의 병용 제형물 |
| US10034893B2 (en) | 2013-02-01 | 2018-07-31 | Enanta Pharmaceuticals, Inc. | 5, 6-D2 uridine nucleoside/tide derivatives |
| US9339541B2 (en) | 2013-03-04 | 2016-05-17 | Merck Sharp & Dohme Corp. | Thiophosphate nucleosides for the treatment of HCV |
| WO2014137926A1 (en) | 2013-03-04 | 2014-09-12 | Idenix Pharmaceuticals, Inc. | 3'-deoxy nucleosides for the treatment of hcv |
| WO2014160484A1 (en) | 2013-03-13 | 2014-10-02 | Idenix Pharmaceuticals, Inc. | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| WO2014165542A1 (en) | 2013-04-01 | 2014-10-09 | Idenix Pharmaceuticals, Inc. | 2',4'-fluoro nucleosides for the treatment of hcv |
| EP3004130B1 (en) | 2013-06-05 | 2019-08-07 | Idenix Pharmaceuticals LLC. | 1',4'-thio nucleosides for the treatment of hcv |
| EP3027636B1 (en) | 2013-08-01 | 2022-01-05 | Idenix Pharmaceuticals LLC | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
| EP3650014B1 (en) | 2013-08-27 | 2021-10-06 | Gilead Pharmasset LLC | Combination formulation of two antiviral compounds |
| CN104447923B (zh) * | 2013-09-23 | 2018-03-30 | 中国药科大学 | 2’‑脱氧‑2’‑氟‑2’‑甲基核苷衍生物及其制备方法与在制药中的用途 |
| EP3131914B1 (en) | 2014-04-16 | 2023-05-10 | Idenix Pharmaceuticals LLC | 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv |
| WO2016033164A1 (en) | 2014-08-26 | 2016-03-03 | Enanta Pharmaceuticals, Inc. | Nucleoside and nucleotide derivatives |
| WO2016042576A1 (en) | 2014-09-16 | 2016-03-24 | Cadila Healthcare Limited | Co-crystal of sofosbuvir and amino acid and process for preparation thereof |
| CN104744539A (zh) * | 2014-09-19 | 2015-07-01 | 上海皓元生物医药科技有限公司 | 一种(2’r)-2’-脱氧-2’-氟-2’-甲基脲苷的合成方法 |
| CN104327138B (zh) * | 2014-10-21 | 2017-05-10 | 齐鲁制药有限公司 | Psi‑7977中间体化合物的制备方法 |
| WO2016073756A1 (en) | 2014-11-06 | 2016-05-12 | Enanta Pharmaceuticals, Inc. | Deuterated nucleoside/tide derivatives |
| US9732110B2 (en) | 2014-12-05 | 2017-08-15 | Enanta Pharmaceuticals, Inc. | Nucleoside and nucleotide derivatives |
| CN104610404B (zh) * | 2015-01-16 | 2016-04-06 | 南通常佑药业科技有限公司 | 一种呋喃核糖磷酸酯衍生物的制备方法 |
| MY190867A (en) | 2015-03-06 | 2022-05-13 | Atea Pharmaceuticals Inc | ? -d-2'-deoxy-2'-?-fluoro-2'- ? -c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment |
| CN104829672B (zh) * | 2015-05-19 | 2018-03-13 | 江苏福瑞生物医药有限公司 | 一种药物中间体的合成方法 |
| CN105061535A (zh) * | 2015-09-02 | 2015-11-18 | 江苏科本医药化学有限公司 | 一种索非布韦中间体的合成方法 |
| CN106554333B (zh) * | 2015-09-29 | 2018-11-30 | 江苏福瑞生物医药有限公司 | 一种药物中间体的合成方法 |
| CN106608896B (zh) * | 2015-10-26 | 2019-08-27 | 江苏福瑞康泰药业有限公司 | 一种药物中间体的合成方法 |
| CN105418547A (zh) * | 2015-11-17 | 2016-03-23 | 海门慧聚药业有限公司 | 索非布韦关键中间体的制备 |
| CN105503983B (zh) * | 2015-12-17 | 2019-06-28 | 江苏阿尔法药业有限公司 | 索菲布韦中间体及其衍生物的制备方法 |
| CN105566422B (zh) * | 2015-12-29 | 2019-06-25 | 江苏阿尔法药业有限公司 | 索菲布韦中间体或其衍生物的制备方法 |
| US11192914B2 (en) | 2016-04-28 | 2021-12-07 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| US10711029B2 (en) | 2016-07-14 | 2020-07-14 | Atea Pharmaceuticals, Inc. | Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| US10239910B2 (en) | 2016-07-20 | 2019-03-26 | Optimus Drugs (P) Limited | Process for the preparation of sofosbuvir |
| PL3512863T3 (pl) | 2016-09-07 | 2022-04-04 | Atea Pharmaceuticals, Inc. | 2'-Podstawione-N6-podstawione nukleotydy purynowe do leczenia zakażeń wirusem RNA |
| IL295609B2 (en) | 2017-02-01 | 2023-11-01 | Atea Pharmaceuticals Inc | Nucleotide hemisulfate salt for the treatment of hepatitis C virus |
| CN106810515A (zh) * | 2017-02-06 | 2017-06-09 | 抚州市星辰药业有限公司 | 一种合成索非布韦的中间体化合物及其合成方法 |
| CN109422789A (zh) * | 2017-08-28 | 2019-03-05 | 常州制药厂有限公司 | 一种索非布韦的制备工艺改进方法 |
| CN112351799A (zh) | 2018-04-10 | 2021-02-09 | 阿堤亚制药公司 | 具有硬化的hcv感染患者的治疗 |
| CN108675984A (zh) * | 2018-06-22 | 2018-10-19 | 江苏阿尔法药业有限公司 | 索非布韦中间体的制备方法 |
| CN111606961A (zh) * | 2019-02-26 | 2020-09-01 | 顾世海 | 一种(2’r)-2’-脱氧-2’-氟-2’-甲基脲苷的工艺生产方法 |
| CN111040010A (zh) * | 2019-12-23 | 2020-04-21 | 上海红蓝医药科技有限公司 | 一种索非布韦中间体的合成方法 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| BR112023026356A2 (pt) | 2021-06-17 | 2024-03-05 | Atea Pharmaceuticals Inc | Método para tratar vírus da hepatite c ou uma condição resultante de uma infecção por hepatite c, combinação, uso da combinação, composição farmacêutica, e, kit para o tratamento de vírus da hepatite c |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006012440A2 (en) * | 2004-07-21 | 2006-02-02 | Pharmasset, Inc. | Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives |
| WO2006031725A2 (en) * | 2004-09-14 | 2006-03-23 | Pharmasset, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR850002973A (ko) * | 1983-10-03 | 1985-05-28 | 구라바야시 이꾸시로 | 시티딘 유도체의 제조방법 |
| JP2559917B2 (ja) * | 1990-06-15 | 1996-12-04 | 三共株式会社 | ピリミジンヌクレオシド誘導体 |
| US5637688A (en) * | 1994-12-13 | 1997-06-10 | Eli Lilly And Company | Process for preparing 1-(2'-deoxy-2'-difluoro-d-ribofuranosyl)-4-aminopyrimidin-2-one hydrochloride |
| IL138037A0 (en) | 1998-02-25 | 2001-10-31 | Univ Emory | 2'-fluoronucleosides |
| AU6388900A (en) | 1999-07-30 | 2001-02-19 | Abbott Gmbh & Co. Kg | 2-pyrazolin-5-ones |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| CZ301182B6 (cs) | 2000-05-26 | 2009-12-02 | Idenix (Cayman) Limited | Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| HUP0400726A3 (en) | 2001-01-22 | 2007-05-29 | Merck & Co Inc | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| WO2003026589A2 (en) | 2001-09-28 | 2003-04-03 | Idenix (Cayman) Limited | Methods and compositions for treating hepatitis c virus using 4'-modified nucleosides |
| WO2004002422A2 (en) | 2002-06-28 | 2004-01-08 | Idenix (Cayman) Limited | 2’-c-methyl-3’-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| TW200500375A (en) | 2002-06-28 | 2005-01-01 | Idenix Cayman Ltd | Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| ES2624353T3 (es) | 2002-11-15 | 2017-07-13 | Idenix Pharmaceuticals Llc | 2'-Metil nucleósidos en combinación con interferón y mutación de Flaviviridae |
| TWI332507B (en) | 2002-11-19 | 2010-11-01 | Hoffmann La Roche | Antiviral nucleoside derivatives |
| EP4032897B1 (en) | 2003-05-30 | 2025-01-29 | Gilead Pharmasset LLC | Modified fluorinated nucleoside analogues |
| ATE478886T1 (de) | 2003-07-25 | 2010-09-15 | Idenix Pharmaceuticals Inc | Purin nucleoside für die behandlung von durch flavividrae verursachten krankheiten, einschliesslich hepatitis c |
| CA2537114C (en) | 2003-08-27 | 2012-10-02 | Biota, Inc. | Tricyclic nucleosides or nucleotides as therapeutic agents |
| CA2565013C (en) * | 2004-04-30 | 2013-01-08 | Daiichi Pharmaceutical Co., Ltd. | Method for producing pentacyclic taxans |
-
2007
- 2007-10-05 WO PCT/US2007/021548 patent/WO2008045419A1/en not_active Ceased
- 2007-10-05 RU RU2009117396/04A patent/RU2421461C2/ru not_active IP Right Cessation
- 2007-10-05 SI SI200731311T patent/SI2084174T1/sl unknown
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- 2007-10-05 BR BRPI0719174A patent/BRPI0719174A2/pt not_active IP Right Cessation
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2009
- 2009-04-07 IL IL198086A patent/IL198086A/en active IP Right Grant
- 2009-04-13 GT GT200900080A patent/GT200900080A/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006012440A2 (en) * | 2004-07-21 | 2006-02-02 | Pharmasset, Inc. | Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives |
| WO2006031725A2 (en) * | 2004-09-14 | 2006-03-23 | Pharmasset, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
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| ES2429290T3 (es) | 2013-11-14 |
| IL198086A0 (en) | 2009-12-24 |
| EP2084174B1 (en) | 2013-07-31 |
| HK1133889A1 (en) | 2010-04-09 |
| BRPI0719174A2 (pt) | 2017-06-13 |
| US8912321B2 (en) | 2014-12-16 |
| CN101600725B (zh) | 2014-11-26 |
| PT2084174E (pt) | 2013-10-08 |
| GT200900080A (es) | 2012-04-10 |
| US20080139802A1 (en) | 2008-06-12 |
| MX2009003795A (es) | 2009-06-18 |
| SI2084174T1 (sl) | 2013-10-30 |
| KR20090060460A (ko) | 2009-06-12 |
| JP2010505954A (ja) | 2010-02-25 |
| RU2421461C2 (ru) | 2011-06-20 |
| IL198086A (en) | 2012-03-29 |
| CN101600725A (zh) | 2009-12-09 |
| CA2666098A1 (en) | 2008-04-17 |
| RU2009117396A (ru) | 2010-11-20 |
| AU2007307057B2 (en) | 2011-09-15 |
| PL2084174T3 (pl) | 2013-12-31 |
| DK2084174T3 (da) | 2013-11-04 |
| US20100056770A1 (en) | 2010-03-04 |
| AU2007307057A1 (en) | 2008-04-17 |
| CA2666098C (en) | 2012-09-25 |
| WO2008045419A1 (en) | 2008-04-17 |
| EP2084174A1 (en) | 2009-08-05 |
| JP5252459B2 (ja) | 2013-07-31 |
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