ES2320136T3 - Metodo industrial para separacion y purificacion de fentanilo por cromatografia preparativa en fase inversa. - Google Patents
Metodo industrial para separacion y purificacion de fentanilo por cromatografia preparativa en fase inversa. Download PDFInfo
- Publication number
- ES2320136T3 ES2320136T3 ES04796374T ES04796374T ES2320136T3 ES 2320136 T3 ES2320136 T3 ES 2320136T3 ES 04796374 T ES04796374 T ES 04796374T ES 04796374 T ES04796374 T ES 04796374T ES 2320136 T3 ES2320136 T3 ES 2320136T3
- Authority
- ES
- Spain
- Prior art keywords
- fentanyl
- acid
- column
- range
- aqueous solution
- 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 - Lifetime
Links
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 title claims abstract description 75
- 229960002428 fentanyl Drugs 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 238000004587 chromatography analysis Methods 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title abstract description 5
- 238000000746 purification Methods 0.000 title description 12
- 238000000926 separation method Methods 0.000 title description 12
- 238000000034 method Methods 0.000 claims description 65
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 21
- 239000000243 solution Substances 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 230000005526 G1 to G0 transition Effects 0.000 claims description 12
- 150000007513 acids Chemical class 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 9
- 239000003446 ligand Substances 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 150000001343 alkyl silanes Chemical class 0.000 claims description 2
- 150000007860 aryl ester derivatives Chemical class 0.000 claims description 2
- 150000008378 aryl ethers Chemical class 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- QTLFDCJYRAHUCF-UHFFFAOYSA-N methoxy-[2-(oxiran-2-ylmethoxy)ethyl]silane Chemical compound CO[SiH2]CCOCC1CO1 QTLFDCJYRAHUCF-UHFFFAOYSA-N 0.000 claims description 2
- 125000002347 octyl 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])[H] 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004079 stearyl 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])C([H])([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 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 150000005215 alkyl ethers Chemical class 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- FPLYNRPOIZEADP-UHFFFAOYSA-N octylsilane Chemical compound CCCCCCCC[SiH3] FPLYNRPOIZEADP-UHFFFAOYSA-N 0.000 claims 1
- 238000012856 packing Methods 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 238000004262 preparative liquid chromatography Methods 0.000 abstract description 5
- 239000012535 impurity Substances 0.000 description 17
- 238000005070 sampling Methods 0.000 description 15
- 238000004237 preparative chromatography Methods 0.000 description 11
- 238000001556 precipitation Methods 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 229930013930 alkaloid Natural products 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000010828 elution Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 150000003797 alkaloid derivatives Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 238000012435 analytical chromatography Methods 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- -1 salt citrate Chemical class 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000008040 ionic compounds Chemical class 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000004081 narcotic agent Substances 0.000 description 2
- 239000003690 nonionic contrast media Substances 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012798 spherical particle Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZTVQQQVZCWLTDF-UHFFFAOYSA-N Remifentanil Chemical compound C1CN(CCC(=O)OC)CCC1(C(=O)OC)N(C(=O)CC)C1=CC=CC=C1 ZTVQQQVZCWLTDF-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 229960001391 alfentanil Drugs 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical compound Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 229960001595 lincomycin hydrochloride Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- DUGOZIWVEXMGBE-STQMWFEESA-N methyl (S)-phenyl[(S)-piperidin-2-yl]acetate Chemical compound C([C@H]1[C@@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-STQMWFEESA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- LHCBOXPPRUIAQT-UHFFFAOYSA-N n-phenyl-n-[1-(2-phenylethyl)piperidin-4-yl]propanamide;hydrochloride Chemical class Cl.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 LHCBOXPPRUIAQT-UHFFFAOYSA-N 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960003394 remifentanil Drugs 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/32—Bonded phase chromatography
- B01D15/325—Reversed phase
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
- B01J20/287—Non-polar phases; Reversed phases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Hydrogenated Pyridines (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51527403P | 2003-10-29 | 2003-10-29 | |
| US515274P | 2003-10-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2320136T3 true ES2320136T3 (es) | 2009-05-19 |
Family
ID=34572823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04796374T Expired - Lifetime ES2320136T3 (es) | 2003-10-29 | 2004-10-22 | Metodo industrial para separacion y purificacion de fentanilo por cromatografia preparativa en fase inversa. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7728145B2 (deFl) |
| EP (1) | EP1682505B1 (deFl) |
| JP (1) | JP2007509945A (deFl) |
| CN (1) | CN100509785C (deFl) |
| AT (1) | ATE418544T1 (deFl) |
| AU (1) | AU2004287815B2 (deFl) |
| CA (1) | CA2544195A1 (deFl) |
| DE (1) | DE602004018674D1 (deFl) |
| ES (1) | ES2320136T3 (deFl) |
| MX (1) | MX264489B (deFl) |
| WO (1) | WO2005044798A1 (deFl) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7486949B2 (en) * | 2004-03-10 | 2009-02-03 | Broadcom Corporation | Method for re-establishing telephone calls after unintended termination |
| WO2006055321A2 (en) * | 2004-11-10 | 2006-05-26 | Boehringer Ingelheim Chemicals, Inc. | Process of making fentanyl intermediates |
| WO2010033540A1 (en) * | 2008-09-19 | 2010-03-25 | Mallinckrodt Inc. | Crystalline forms of fentanyl alkaloid |
| US9724622B2 (en) * | 2013-01-29 | 2017-08-08 | Neuland Health Sciences Private Limited | Purification of organic compounds using surrogate stationary phases on reversed phase columns |
| EP3046643A4 (en) * | 2013-09-20 | 2017-05-03 | Davuluri, Ramamohan Rao | Purification of organic compounds by surfactant mediated preparative hplc |
| US20220395767A1 (en) * | 2021-06-15 | 2022-12-15 | Perkinelmer Health Sciences, Inc. | Enhancing lcms analyte signals |
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| NL284196A (deFl) * | 1961-10-10 | |||
| US4234684A (en) * | 1979-12-11 | 1980-11-18 | Eli Lilly And Company | Method of preparing mycophenolic acid glucoside |
| US4293489A (en) * | 1979-12-13 | 1981-10-06 | Eli Lilly And Company | Derivatives of A-30912A nucleus |
| US4317903A (en) * | 1981-01-26 | 1982-03-02 | The Upjohn Company | Process for the purification of lincomycin |
| US4336333A (en) * | 1981-03-13 | 1982-06-22 | Eli Lilly And Company | Process for preparing tunicamycin |
| US4916142A (en) * | 1987-02-02 | 1990-04-10 | Boc, Inc. | N-heterocyclic-N-(4-piperidinyl)amides and pharmaceutical compositions and their use as analgesics |
| US4904590A (en) * | 1988-12-27 | 1990-02-27 | Eli Lilly And Company | Antibiotic A80915 and process for its production |
| US5780589A (en) * | 1994-11-30 | 1998-07-14 | The United States Of America As Represented By The Department Of Health And Human Services | Ultraselective opioidmimetic peptides and pharmacological and therapeutic uses thereof |
| AU744950B2 (en) * | 1998-02-03 | 2002-03-07 | Arqule, Inc. | Rapid method for separation of small molecules using reverse phase high performance liquid chromatography |
| WO2001040184A2 (en) * | 1999-12-06 | 2001-06-07 | Mallinckrodt Inc. | Methods for the syntheses of alfentanil, sufentanil and remifentanil |
| US7671203B2 (en) * | 2002-02-28 | 2010-03-02 | Mallinckrodt Inc. | Method and system for separation and purification of at least one narcotic alkaloid using reverse phase preparative chromatography |
| ITRM20020458A1 (it) | 2002-09-13 | 2004-03-14 | Ambiotec S A S Di Ammendola Sergio | Procedimento per la separazione preparativa degli epimeri di steroidi. |
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- 2004-10-22 EP EP04796374A patent/EP1682505B1/en not_active Expired - Lifetime
- 2004-10-22 DE DE602004018674T patent/DE602004018674D1/de not_active Expired - Fee Related
- 2004-10-22 CA CA002544195A patent/CA2544195A1/en not_active Abandoned
- 2004-10-22 US US10/574,545 patent/US7728145B2/en not_active Expired - Fee Related
- 2004-10-22 JP JP2006538157A patent/JP2007509945A/ja not_active Withdrawn
- 2004-10-22 CN CNB2004800321721A patent/CN100509785C/zh not_active Expired - Fee Related
- 2004-10-22 ES ES04796374T patent/ES2320136T3/es not_active Expired - Lifetime
- 2004-10-22 AT AT04796374T patent/ATE418544T1/de not_active IP Right Cessation
- 2004-10-22 WO PCT/US2004/035386 patent/WO2005044798A1/en active Application Filing
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2006
- 2006-04-27 MX MXPA06004711 patent/MX264489B/es active IP Right Grant
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| CN1874999A (zh) | 2006-12-06 |
| WO2005044798A1 (en) | 2005-05-19 |
| MXPA06004711A (es) | 2006-07-20 |
| US7728145B2 (en) | 2010-06-01 |
| CA2544195A1 (en) | 2005-05-19 |
| MX264489B (en) | 2009-02-12 |
| EP1682505B1 (en) | 2008-12-24 |
| AU2004287815A1 (en) | 2005-05-19 |
| JP2007509945A (ja) | 2007-04-19 |
| EP1682505A1 (en) | 2006-07-26 |
| DE602004018674D1 (de) | 2009-02-05 |
| US20070123710A1 (en) | 2007-05-31 |
| AU2004287815B2 (en) | 2009-05-28 |
| ATE418544T1 (de) | 2009-01-15 |
| CN100509785C (zh) | 2009-07-08 |
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