JPS621399B2 - - Google Patents
Info
- Publication number
- JPS621399B2 JPS621399B2 JP15292279A JP15292279A JPS621399B2 JP S621399 B2 JPS621399 B2 JP S621399B2 JP 15292279 A JP15292279 A JP 15292279A JP 15292279 A JP15292279 A JP 15292279A JP S621399 B2 JPS621399 B2 JP S621399B2
- Authority
- JP
- Japan
- Prior art keywords
- fluorouridine
- isopropylidene
- proton
- mmol
- chloroform
- 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
Links
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims description 17
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- -1 phenylacetyl Chemical group 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 10
- LHTMLCXJMYPWGR-NPDIDSPYSA-N 5-fluoro-1-[(4r,6r)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione Chemical compound N1([C@@H]2O[C@H](CO)C3OC(OC32)(C)C)C=C(F)C(=O)NC1=O LHTMLCXJMYPWGR-NPDIDSPYSA-N 0.000 description 10
- 235000013736 caramel Nutrition 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001408 amides Chemical group 0.000 description 5
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000001118 alkylidene group Chemical group 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- MVGLBXWFOSHCCP-UHFFFAOYSA-N chloroform;tetrachloromethane Chemical compound ClC(Cl)Cl.ClC(Cl)(Cl)Cl MVGLBXWFOSHCCP-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000009876 antimalignant effect Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- OEAFZNRGZZNREY-SEFVSHJNSA-N 1-o-benzyl 2-o-[[(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl] (2s)-pyrrolidine-1,2-dicarboxylate Chemical compound C([C@H]1C(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C(NC(=O)C(F)=C2)=O)CCN1C(=O)OCC1=CC=CC=C1 OEAFZNRGZZNREY-SEFVSHJNSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- HRBGUGQWTMBDTR-UHFFFAOYSA-N 2,3,4-tri(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC=C(S(Cl)(=O)=O)C(C(C)C)=C1C(C)C HRBGUGQWTMBDTR-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- ZCXMFBUYRUWFAQ-PBEGBBSFSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-2-(butanoylamino)-3-methylbutanoate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)[C@H](C(C)C)NC(=O)CCC)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZCXMFBUYRUWFAQ-PBEGBBSFSA-N 0.000 description 2
- FKEFWONOONUTEI-FSNPWBFUSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoate Chemical compound N([C@@H](C(C)C)C(=O)OC[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)C(=O)OCC1=CC=CC=C1 FKEFWONOONUTEI-FSNPWBFUSA-N 0.000 description 2
- GLPMXIIHERHMQE-QBRBXANFSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@H](C(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 GLPMXIIHERHMQE-QBRBXANFSA-N 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229960004441 tyrosine Drugs 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QUCAHWMUAMQNFV-IBGZPJMESA-N (2S)-3-(4-hydroxyphenyl)-2-[pentanoyloxy(phenylmethoxycarbonyl)amino]propanoic acid Chemical compound C(CCCC)(=O)ON([C@@H](CC1=CC=C(C=C1)O)C(=O)O)C(=O)OCC1=CC=CC=C1 QUCAHWMUAMQNFV-IBGZPJMESA-N 0.000 description 1
- JXGVXCZADZNAMJ-NSHDSACASA-N (2s)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 JXGVXCZADZNAMJ-NSHDSACASA-N 0.000 description 1
- PECAWSDTQIFOPF-ZDUSSCGKSA-N (2s)-2-(decanoylamino)-4-methylsulfanylbutanoic acid Chemical compound CCCCCCCCCC(=O)N[C@H](C(O)=O)CCSC PECAWSDTQIFOPF-ZDUSSCGKSA-N 0.000 description 1
- CGTHEWLEJCUUCV-IBGZPJMESA-N (2s)-2-(pentanoylamino)-3-(4-phenylmethoxycarbonyloxyphenyl)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)CCCC)C(O)=O)=CC=C1OC(=O)OCC1=CC=CC=C1 CGTHEWLEJCUUCV-IBGZPJMESA-N 0.000 description 1
- RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 1
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- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YRQCXKWIUIJBJN-YSSBGUOXSA-N 1-[(2r,3r,4s,5s)-3,4-dihydroxy-5-(1-hydroxy-2-methylprop-1-enyl)oxolan-2-yl]-5-fluoropyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](C(O)=C(C)C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 YRQCXKWIUIJBJN-YSSBGUOXSA-N 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
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- FAIZHAKOWDWMMK-ZAPJKBGESA-N [(2R,3S,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C(C1=CC=CC=C1)OC(=O)N[C@@H](CO)C(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(=O)NC(=O)C(=C1)F)O)O FAIZHAKOWDWMMK-ZAPJKBGESA-N 0.000 description 1
- AFOUITUOOKDECA-YWCCWUOUSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2r)-3-benzylsulfanyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@H](C(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)O)NC(=O)OCC=1C=CC=CC=1)SCC1=CC=CC=C1 AFOUITUOOKDECA-YWCCWUOUSA-N 0.000 description 1
- LZDZKYWQWUCFNC-PJDYVGSDSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-3-(4-hydroxyphenyl)-2-(pentanoylamino)propanoate Chemical compound C([C@H](NC(=O)CCCC)C(=O)OC[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)C1=CC=C(O)C=C1 LZDZKYWQWUCFNC-PJDYVGSDSA-N 0.000 description 1
- XOLYMOAEPXAVGQ-PJDYVGSDSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-4-methylsulfanyl-2-(3-phenylpropanoylamino)butanoate Chemical compound N([C@@H](CCSC)C(=O)OC[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)C(=O)CCC1=CC=CC=C1 XOLYMOAEPXAVGQ-PJDYVGSDSA-N 0.000 description 1
- DYADTGFGLFIFLN-LMWHNAIISA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-4-methylsulfanyl-2-(pentanoylamino)butanoate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)[C@H](CCSC)NC(=O)CCCC)O[C@H]1N1C(=O)NC(=O)C(F)=C1 DYADTGFGLFIFLN-LMWHNAIISA-N 0.000 description 1
- ZCGHCZMVDSJOFI-SEFVSHJNSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2s)-4-methylsulfanyl-2-(phenylmethoxycarbonylamino)butanoate Chemical compound N([C@@H](CCSC)C(=O)OC[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C(NC(=O)C(F)=C1)=O)O)C(=O)OCC1=CC=CC=C1 ZCGHCZMVDSJOFI-SEFVSHJNSA-N 0.000 description 1
- NYJHRXPVSDZAFU-DNNBLBMLSA-N [(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl 2-(phenylmethoxycarbonylamino)acetate Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C(NC(=O)C(F)=C1)=O)OC(=O)CNC(=O)OCC1=CC=CC=C1 NYJHRXPVSDZAFU-DNNBLBMLSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-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
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15292279A JPS5677298A (en) | 1979-11-28 | 1979-11-28 | Movel 5-fluorouridine derivative and its preparation |
| US06/210,796 US4340728A (en) | 1979-11-28 | 1980-11-26 | Nucleoside derivatives and process for preparing same |
| IT26289/80A IT1141100B (it) | 1979-11-28 | 1980-11-27 | Derivati nucleosidici e processo per la loro preparazione |
| DE19803044740 DE3044740A1 (de) | 1979-11-28 | 1980-11-27 | Nucleosidderivate, ihre herstellung und pharmazeutische mittel |
| CH883380A CH646441A5 (de) | 1979-11-28 | 1980-11-28 | Nucleosidderivate, ihre herstellung und diese enthaltende pharmazeutische mittel. |
| FR8025348A FR2470774A1 (fr) | 1979-11-28 | 1980-11-28 | Derives de nucleosides, leur preparation et leurs utilisations therapeutiques |
| GB8038211A GB2066812B (en) | 1979-11-28 | 1980-11-28 | 5'-acyl-uridine derivatives and processes for the preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15292279A JPS5677298A (en) | 1979-11-28 | 1979-11-28 | Movel 5-fluorouridine derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5677298A JPS5677298A (en) | 1981-06-25 |
| JPS621399B2 true JPS621399B2 (pl) | 1987-01-13 |
Family
ID=15551073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15292279A Granted JPS5677298A (en) | 1979-11-28 | 1979-11-28 | Movel 5-fluorouridine derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5677298A (pl) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61134397A (ja) * | 1984-12-01 | 1986-06-21 | Fuji Kagaku Kogyo Kk | ５’−０−オリゴペプチジル−５−フルオロウリジン及びその製造方法 |
| JPS61246196A (ja) * | 1985-04-22 | 1986-11-01 | Fuji Kagaku Kogyo Kk | ５′−０−アシル−５−フルオロウリジン及びその製造方法 |
| DE3686266T2 (de) * | 1986-05-30 | 1993-03-11 | Fuji Chem Ind Co Ltd | Neue 5-fluoruridin-verbindungen und deren herstellung. |
-
1979
- 1979-11-28 JP JP15292279A patent/JPS5677298A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5677298A (en) | 1981-06-25 |
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