JP4603274B2 - 2’−デオキシ−5−トリフルオロメチルウリジンの製造方法 - Google Patents
2’−デオキシ−5−トリフルオロメチルウリジンの製造方法 Download PDFInfo
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- JP4603274B2 JP4603274B2 JP2004047339A JP2004047339A JP4603274B2 JP 4603274 B2 JP4603274 B2 JP 4603274B2 JP 2004047339 A JP2004047339 A JP 2004047339A JP 2004047339 A JP2004047339 A JP 2004047339A JP 4603274 B2 JP4603274 B2 JP 4603274B2
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- Prior art keywords
- deoxy
- trifluoromethyluridine
- organic solvent
- aqueous solution
- producing
- Prior art date
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- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 title claims description 40
- 238000000034 method Methods 0.000 title claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 7
- 239000012046 mixed solvent Substances 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 238000006911 enzymatic reaction Methods 0.000 claims description 6
- 150000008282 halocarbons Chemical class 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 238000001308 synthesis method Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- LMNPKIOZMGYQIU-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrimidine-2,4-dione Chemical class FC(F)(F)C1=CNC(=O)NC1=O LMNPKIOZMGYQIU-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VHFDCHXRWYAMBQ-VPCXQMTMSA-N FC[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=C1 Chemical compound FC[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=C1 VHFDCHXRWYAMBQ-VPCXQMTMSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- BLGKEJUTTUUIEN-IUYQGCFVSA-N (3s,4r)-3,4,5-trihydroxypentanoyl chloride Chemical compound OC[C@@H](O)[C@@H](O)CC(Cl)=O BLGKEJUTTUUIEN-IUYQGCFVSA-N 0.000 description 1
- GLXNCCKMEDEHOO-UHFFFAOYSA-N 1,1,1-trifluoro-n-nitroso-n-(trifluoromethyl)methanesulfonamide Chemical compound FC(F)(F)N(N=O)S(=O)(=O)C(F)(F)F GLXNCCKMEDEHOO-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- KBDKAJNTYKVSEK-VPENINKCSA-N 2-deoxy-alpha-D-ribose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)C[C@@H]1O KBDKAJNTYKVSEK-VPENINKCSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 101710132082 Pyrimidine/purine nucleoside phosphorylase Proteins 0.000 description 1
- 102000013537 Thymidine Phosphorylase Human genes 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 229910001963 alkali metal nitrate Inorganic materials 0.000 description 1
- 229910052936 alkali metal sulfate Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 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
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940097364 magnesium acetate tetrahydrate Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- XKPKPGCRSHFTKM-UHFFFAOYSA-L magnesium;diacetate;tetrahydrate Chemical compound O.O.O.O.[Mg+2].CC([O-])=O.CC([O-])=O XKPKPGCRSHFTKM-UHFFFAOYSA-L 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- XHBKWMUWFRURGS-UHFFFAOYSA-N trimethyl-[5-(trifluoromethyl)-2-trimethylsilyloxypyrimidin-4-yl]oxysilane Chemical compound C[Si](C)(C)OC1=NC=C(C(F)(F)F)C(O[Si](C)(C)C)=N1 XHBKWMUWFRURGS-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
1)5−トリフルオロメチルウラシル誘導体をトリアルキルシリル化し、水酸基を保護した1−クロロ−2−デオキシリボースと触媒存在下、反応させ、次いで脱保護して目的物を得る方法。(特許文献1)
2)水酸基を保護した2’−デオキシウリジン誘導体にN−トリフルオロメチル−N−ニトロソトリフルオロメタンスルホンアミドを反応させトリフルオロメチル化後、脱保護して目的物を得る方法。(特許文献2)
3)ヌクレオシド−2’−デオキシリボース転移酵素を用いて、チミジンと5−トリフルオロメチルウラシルの核酸塩基交換反応を行い、目的物を得る方法。(特許文献3)
カラム:YMC AM−313(250mm×直径6mm)
流速:1mL/min.
カラム温度:40℃
検出波長:254nm
移動相:20mmolの酢酸アンモニウム水溶液(2.7L)に酢酸を加えpHを3.5に調整した後、MeOH(0.3L)を加え混和し、脱気する。
内標準物質:ニコチン酸
2’−デオキシ−5−トリフルオロメチルウリジンの製造
2−デオキシリボース−1−リン酸・2アンモニウム塩20g、水酸化マグネシウム1.82g、酢酸マグネシウム4水和物20g、5−トリフルオロメチルウラシル13.2gを88gの水に懸濁し、Sigma社より入手したチミジンホスフォリラーゼ2gを加え、30℃で7時間反応する。反応終了後、HPLCで目的物を分析した所、2’−デオキシ−5−トリフルオロメチルウリジンの収率は5−トリフルオロメチルウラシルに対し95モル%であった。
2’−デオキシ−5−トリフルオロメチルウリジンの製造
5−トリフルオロメチル−2,4−ビス(トリメチルシリルオキシ)ピリミジン4gの無水クロロホルム溶液25mlに塩化亜鉛60mgを加えた後、1−クロロ−2−デオキシ−3,5−ジ−O−p−クロロベンゾイル−α−D−エリスロ−ペントフラノース1.3gを加え、室温で15時間反応した。反応終了後、反応溶液を炭酸水素ナトリウム水溶液にあけ、クロロホルムで抽出、有機層を無水硫酸マグネシウムで乾燥し、溶媒を減圧濃縮した。得られた残留物をエタノールから結晶化して、O3’、O5’−ビス(p−クロロベンゾイル)−2’−デオキシ−5−トリフルオロメチルウラシル1.4gを得た。
Claims (1)
- 合成法又は酵素法により得られる、一般式(1)[化1]
で表される2’−デオキシ−5−トリフルオロメチルウリジンを含有するpH1〜4の水溶液に、メタノール、エタノール、イソプロパノール、メチルセルソルブ、アセトン、テトラヒドロフラン、ジメトキシエタン、ジメチルホルムアミド、ジメチルイミダゾリジノン、及びジメチルスルホキシドからなる群より選択されるいずれか1つの有機溶媒と、ハロゲン化炭化水素類、エーテル類、及びメチルイソブチルケトンからなる群より選択されるいずれか1つの有機溶媒との混合溶媒の存在下、無機塩を溶解させ、該混合溶媒中に2’−デオキシ−5−トリフルオロメチルウリジンを抽出する工程を含むことを特徴とする2’−デオキシ−5−トリフルオロメチルウリジンの製造方法。
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Publications (2)
Publication Number | Publication Date |
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JP2005239552A JP2005239552A (ja) | 2005-09-08 |
JP4603274B2 true JP4603274B2 (ja) | 2010-12-22 |
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Cited By (4)
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WO2019124544A1 (ja) | 2017-12-22 | 2019-06-27 | 大鵬薬品工業株式会社 | トリフルリジン及び/又はチピラシル由来の類縁物質の検出方法 |
WO2019135405A1 (ja) | 2018-01-05 | 2019-07-11 | 大鵬薬品工業株式会社 | トリフルリジン由来の類縁物質の検出方法 |
US10809237B2 (en) | 2018-01-05 | 2020-10-20 | Taiho Pharmaceutical Co., Ltd. | Method for detecting trifluridine-related substance by high-performance liquid chromatography |
US10866219B2 (en) | 2017-12-22 | 2020-12-15 | Taiho Pharmaceutical Co., Ltd. | Method for detecting trifluridine- and/or tipiracil-related substance |
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CN105198946A (zh) * | 2014-06-11 | 2015-12-30 | 江苏豪森药业股份有限公司 | 新的曲氟尿苷晶型及其制备方法 |
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WO2019124544A1 (ja) | 2017-12-22 | 2019-06-27 | 大鵬薬品工業株式会社 | トリフルリジン及び/又はチピラシル由来の類縁物質の検出方法 |
US10866219B2 (en) | 2017-12-22 | 2020-12-15 | Taiho Pharmaceutical Co., Ltd. | Method for detecting trifluridine- and/or tipiracil-related substance |
WO2019135405A1 (ja) | 2018-01-05 | 2019-07-11 | 大鵬薬品工業株式会社 | トリフルリジン由来の類縁物質の検出方法 |
US10809237B2 (en) | 2018-01-05 | 2020-10-20 | Taiho Pharmaceutical Co., Ltd. | Method for detecting trifluridine-related substance by high-performance liquid chromatography |
US10816517B2 (en) | 2018-01-05 | 2020-10-27 | Taiho Pharmaceutical Co., Ltd. | Method for detecting trifluridine-related substance by high-performance liquid chromatography |
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