NO311255B1 - Fremgangsmåte for fremstilling av taxanderivater samt mellomprodukter til bruk ved fremstillingen - Google Patents
Fremgangsmåte for fremstilling av taxanderivater samt mellomprodukter til bruk ved fremstillingen Download PDFInfo
- Publication number
- NO311255B1 NO311255B1 NO19951203A NO951203A NO311255B1 NO 311255 B1 NO311255 B1 NO 311255B1 NO 19951203 A NO19951203 A NO 19951203A NO 951203 A NO951203 A NO 951203A NO 311255 B1 NO311255 B1 NO 311255B1
- Authority
- NO
- Norway
- Prior art keywords
- general formula
- residue
- acid
- compound
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 10
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 title claims abstract description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 230000008569 process Effects 0.000 title claims description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 239000000543 intermediate Substances 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 claims abstract description 10
- 229930014667 baccatin III Natural products 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 23
- -1 aliphatic ester Chemical class 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 8
- 239000011707 mineral Substances 0.000 claims description 8
- 235000010755 mineral Nutrition 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 239000010949 copper Substances 0.000 claims description 6
- 150000002170 ethers Chemical class 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 6
- 239000011701 zinc Substances 0.000 claims description 6
- 229910052725 zinc Inorganic materials 0.000 claims description 6
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 claims description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- YWLXLRUDGLRYDR-SKXCCXORSA-N 10-dab iii Chemical class O([C@H]1C2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-SKXCCXORSA-N 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 3
- 229940073608 benzyl chloride Drugs 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 2
- 230000032050 esterification Effects 0.000 abstract description 5
- 238000005886 esterification reaction Methods 0.000 abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 5
- 230000000719 anti-leukaemic effect Effects 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 abstract 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 230000010933 acylation Effects 0.000 abstract 1
- 238000005917 acylation reaction Methods 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 125000003277 amino group Chemical group 0.000 abstract 1
- 150000001602 bicycloalkyls Chemical group 0.000 abstract 1
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 230000008030 elimination Effects 0.000 abstract 1
- 238000003379 elimination reaction Methods 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical group O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 10
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- 150000003738 xylenes Chemical class 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000003927 aminopyridines Chemical class 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000005840 aryl radicals Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- HOJZAHQWDXAPDJ-UHFFFAOYSA-N 3-anilino-2-hydroxypropanoic acid Chemical class OC(=O)C(O)CNC1=CC=CC=C1 HOJZAHQWDXAPDJ-UHFFFAOYSA-N 0.000 description 1
- 150000007579 7-membered cyclic compounds Chemical class 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- GCSAXWHQFYOIFE-UHFFFAOYSA-N dipyridin-2-yl carbonate Chemical compound C=1C=CC=NC=1OC(=O)OC1=CC=CC=N1 GCSAXWHQFYOIFE-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- NCALQERIBRYGOK-NWDGAFQWSA-N methyl (2r,3s)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@@H](O)C(=O)OC)C1=CC=CC=C1 NCALQERIBRYGOK-NWDGAFQWSA-N 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 150000002917 oxazolidines Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9211743A FR2696460B1 (fr) | 1992-10-05 | 1992-10-05 | Procédé de préparation de dérivés du taxane. |
| PCT/FR1993/000969 WO1994007879A1 (fr) | 1992-10-05 | 1993-10-04 | Procede de preparation de derives du taxane |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO951203D0 NO951203D0 (no) | 1995-03-29 |
| NO951203L NO951203L (no) | 1995-03-29 |
| NO311255B1 true NO311255B1 (no) | 2001-11-05 |
Family
ID=9434121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19951203A NO311255B1 (no) | 1992-10-05 | 1995-03-29 | Fremgangsmåte for fremstilling av taxanderivater samt mellomprodukter til bruk ved fremstillingen |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US5621121A (pl) |
| EP (1) | EP0663908B1 (pl) |
| JP (1) | JP3014762B2 (pl) |
| KR (1) | KR100301237B1 (pl) |
| AT (1) | ATE148882T1 (pl) |
| AU (1) | AU690080B2 (pl) |
| CA (1) | CA2146249A1 (pl) |
| CZ (1) | CZ283291B6 (pl) |
| DE (1) | DE69308154T2 (pl) |
| DK (1) | DK0663908T3 (pl) |
| ES (1) | ES2098060T3 (pl) |
| FI (1) | FI951592A0 (pl) |
| FR (1) | FR2696460B1 (pl) |
| GR (1) | GR3022616T3 (pl) |
| HU (1) | HUT72613A (pl) |
| MX (1) | MX9305768A (pl) |
| NO (1) | NO311255B1 (pl) |
| NZ (1) | NZ256447A (pl) |
| PL (1) | PL184556B1 (pl) |
| RU (1) | RU2115649C1 (pl) |
| SK (1) | SK280577B6 (pl) |
| TW (1) | TW393474B (pl) |
| WO (1) | WO1994007879A1 (pl) |
| ZA (1) | ZA937320B (pl) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6794523B2 (en) | 1991-09-23 | 2004-09-21 | Florida State University | Taxanes having t-butoxycarbonyl substituted side-chains and pharmaceutical compositions containing them |
| FR2696460B1 (fr) * | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé de préparation de dérivés du taxane. |
| FR2696464B1 (fr) * | 1992-10-05 | 1994-11-10 | Rhone Poulenc Rorer Sa | Nouveau procédé d'estérification de la baccatine III et de la désacétyl-10 baccatine III. |
| FR2697522B1 (fr) * | 1992-10-30 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé de préparation de dérivés du taxane. |
| FR2698361B1 (fr) * | 1992-11-20 | 1995-01-13 | Rhone Poulenc Rorer Sa | Procédé de préparation d'un acide oxazolidine-1,3 carboxylique-5. |
| IL107950A (en) | 1992-12-15 | 2001-04-30 | Upjohn Co | b 7, b 8 - Matano - Taxols, their preparation and pharmaceutical preparations against malignant tumors containing them |
| US5973160A (en) * | 1992-12-23 | 1999-10-26 | Poss; Michael A. | Methods for the preparation of novel sidechain-bearing taxanes |
| EP1260507A1 (en) | 1993-02-05 | 2002-11-27 | Bryn Mawr College | Synthesis of taxol, analogs and intermediates with variable A-nng side chains |
| ES2242807T3 (es) * | 1993-03-22 | 2005-11-16 | Florida State University | Taxanos que tienen furilo o tienilo sustituido en la cadena lateral sustituida. |
| US5965739A (en) * | 1993-06-11 | 1999-10-12 | Pharmacia & Upjohn Company | Δ6,7 -taxols antineoplastic use and pharmaceutical compositions containing them |
| FR2706457B1 (fr) * | 1993-06-16 | 1995-07-28 | Rhone Poulenc Rorer Sa | Procédé de préparation d'un acide oxazolidinecarboxylique utile pour préparer des taxoïdes thérapeutiquement actifs. |
| EP1247804A1 (en) * | 1993-11-12 | 2002-10-09 | PHARMACIA & UPJOHN COMPANY | Pyrimidine-thioalkyl and alkylether compounds |
| IL127599A (en) * | 1994-01-28 | 2004-06-01 | Upjohn Co | Process for preparing isotaxol analogs |
| US5677470A (en) * | 1994-06-28 | 1997-10-14 | Tanabe Seiyaku Co., Ltd. | Baccatin derivatives and processes for preparing the same |
| CA2170661A1 (en) * | 1995-03-22 | 1996-09-23 | John K. Thottathil | Novel methods for the preparation of taxanes using oaxzolidine intermediates |
| US5688977A (en) * | 1996-02-29 | 1997-11-18 | Napro Biotherapeutics, Inc. | Method for docetaxel synthesis |
| PT1114815E (pt) * | 1996-05-08 | 2005-01-31 | Upjohn Co | Processo para a preparacao de taxol |
| US7288665B1 (en) | 1997-08-18 | 2007-10-30 | Florida State University | Process for selective derivatization of taxanes |
| ATE234800T1 (de) | 1997-08-21 | 2003-04-15 | Univ Florida State | Verfahren zur synthese von taxanen |
| US5917062A (en) * | 1997-11-21 | 1999-06-29 | Indena S.P.A | Intermediates and methods useful in the semisynthesis of paclitaxel and analogs |
| IT1308636B1 (it) | 1999-03-02 | 2002-01-09 | Indena Spa | Procedimento per la preparazione di tassani da 10-desacetilbaccatinaiii. |
| ITMI991483A1 (it) | 1999-07-06 | 2001-01-06 | Indena Spa | Derivati tassanici e procedimenti per la loro preparazione |
| CA2385528C (en) | 1999-10-01 | 2013-12-10 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| CZ2003837A3 (cs) | 2000-09-22 | 2004-12-15 | Bristol-Myers Squibb Company | Způsob pro snížení toxicity při kombinovaných chemoterapiích |
| DE60144113D1 (de) * | 2001-03-23 | 2011-04-07 | Scinopharm Taiwan Ltd | Verfahren zur herstellung von taxanderivaten |
| AU2003273671A1 (en) * | 2002-10-09 | 2004-05-04 | Phytogen Life Sciences, Inc. | Novel taxanes and methods related to use and preparation thereof |
| US7202370B2 (en) * | 2003-10-27 | 2007-04-10 | Conor Medsystems, Inc. | Semi-synthesis of taxane intermediates from 9-dihydro-13-acetylbaccatin III |
| DE102004034140A1 (de) * | 2004-07-15 | 2006-02-23 | Covion Organic Semiconductors Gmbh | Verwendung von Polymeren für Up-conversion und Vorrichtungen zur Up-conversion |
| CA2756603C (en) * | 2006-10-20 | 2013-05-28 | Scinopharm Singapore Pte, Ltd. | Process for making crystalline docetaxel trihydrate |
| KR100847331B1 (ko) * | 2006-12-14 | 2008-07-21 | 한미약품 주식회사 | 도세탁셀의 제조방법 및 이에 사용되는 중간체 |
| ES2389518T3 (es) | 2008-01-18 | 2012-10-26 | Indena S.P.A. | Formas sólidas de ortataxel |
| KR101003820B1 (ko) | 2008-06-19 | 2010-12-27 | 주식회사 셀트리온화학연구소 | 도세탁셀의 제조방법 및 도세탁셀의 제조를 위한 신규한중간체 |
| PL388144A1 (pl) | 2009-05-29 | 2010-12-06 | Przedsiębiorstwo Produkcyjno-Wdrożeniowe Ifotam Spółka Z Ograniczoną Odpowiedzialnością | Solwaty (2R,3S)-3-tert-butoksykarbonylamino-2-hydroksy-3-fenylopropionianu 4-acetoksy-2α-benzoiloksy -5β,20-epoksy-1,7β,10β-trihydroksy-9-okso-taks-11-en-13α-ylu, sposób ich otrzymywania i zastosowanie |
| JP2014079364A (ja) * | 2012-10-16 | 2014-05-08 | Tokai Medical Care Holdings Co Ltd | 歩行訓練補助器 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2601675B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
| MX9102128A (es) * | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
| US5319112A (en) * | 1992-08-18 | 1994-06-07 | Virgnia Tech Intellectual Properties, Inc. | Method for the conversion of cephalomannine to taxol and for the preparation of N-acyl analogs of taxol |
| FR2696460B1 (fr) * | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé de préparation de dérivés du taxane. |
| FR2698871B1 (fr) * | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
| US5965739A (en) * | 1993-06-11 | 1999-10-12 | Pharmacia & Upjohn Company | Δ6,7 -taxols antineoplastic use and pharmaceutical compositions containing them |
-
1992
- 1992-10-05 FR FR9211743A patent/FR2696460B1/fr not_active Expired - Fee Related
-
1993
- 1993-09-21 MX MX9305768A patent/MX9305768A/es not_active IP Right Cessation
- 1993-10-01 ZA ZA937320A patent/ZA937320B/xx unknown
- 1993-10-02 TW TW082108100A patent/TW393474B/zh not_active IP Right Cessation
- 1993-10-04 KR KR1019950701304A patent/KR100301237B1/ko not_active IP Right Cessation
- 1993-10-04 JP JP6508789A patent/JP3014762B2/ja not_active Expired - Fee Related
- 1993-10-04 DE DE69308154T patent/DE69308154T2/de not_active Expired - Fee Related
- 1993-10-04 HU HU9500968A patent/HUT72613A/hu unknown
- 1993-10-04 AT AT93921984T patent/ATE148882T1/de not_active IP Right Cessation
- 1993-10-04 EP EP93921984A patent/EP0663908B1/fr not_active Expired - Lifetime
- 1993-10-04 NZ NZ256447A patent/NZ256447A/en unknown
- 1993-10-04 RU RU95110682/04A patent/RU2115649C1/ru not_active IP Right Cessation
- 1993-10-04 US US08/411,690 patent/US5621121A/en not_active Expired - Fee Related
- 1993-10-04 DK DK93921984.6T patent/DK0663908T3/da active
- 1993-10-04 ES ES93921984T patent/ES2098060T3/es not_active Expired - Lifetime
- 1993-10-04 PL PL93308242A patent/PL184556B1/pl unknown
- 1993-10-04 SK SK434-95A patent/SK280577B6/sk unknown
- 1993-10-04 CA CA002146249A patent/CA2146249A1/fr not_active Abandoned
- 1993-10-04 WO PCT/FR1993/000969 patent/WO1994007879A1/fr active IP Right Grant
- 1993-10-04 CZ CZ95843A patent/CZ283291B6/cs not_active IP Right Cessation
- 1993-10-04 AU AU51152/93A patent/AU690080B2/en not_active Ceased
-
1995
- 1995-03-29 NO NO19951203A patent/NO311255B1/no not_active IP Right Cessation
- 1995-04-04 FI FI951592A patent/FI951592A0/fi unknown
-
1997
- 1997-01-03 US US08/778,637 patent/US5726318A/en not_active Expired - Fee Related
- 1997-02-20 GR GR960402766T patent/GR3022616T3/el unknown
- 1997-10-31 US US08/962,011 patent/US5861515A/en not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
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| MM1K | Lapsed by not paying the annual fees |