UA76826C2 - Способ получения аморфной формы гемикальциевой соли (3r,5r) 7-[3-фенил-4-фенилкарбамоил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидрогептановой кислоты (аторвастатина) - Google Patents
Способ получения аморфной формы гемикальциевой соли (3r,5r) 7-[3-фенил-4-фенилкарбамоил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидрогептановой кислоты (аторвастатина) Download PDFInfo
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- UA76826C2 UA76826C2 UA20040907211A UA20040907211A UA76826C2 UA 76826 C2 UA76826 C2 UA 76826C2 UA 20040907211 A UA20040907211 A UA 20040907211A UA 20040907211 A UA20040907211 A UA 20040907211A UA 76826 C2 UA76826 C2 UA 76826C2
- Authority
- UA
- Ukraine
- Prior art keywords
- solution
- acid
- salt
- phenyl
- phenylcarbamoyl
- Prior art date
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- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 title abstract description 55
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 229960005370 atorvastatin Drugs 0.000 title description 53
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 title description 52
- 239000002253 acid Substances 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims abstract description 9
- 239000000920 calcium hydroxide Substances 0.000 claims abstract description 9
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims abstract description 9
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011575 calcium Substances 0.000 claims abstract description 6
- 150000001983 dialkylethers Chemical class 0.000 claims abstract description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 5
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 5
- 150000001768 cations Chemical class 0.000 claims abstract description 4
- 150000001340 alkali metals Chemical class 0.000 claims abstract 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 99
- 239000000243 solution Substances 0.000 claims description 83
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 66
- 238000000034 method Methods 0.000 claims description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 27
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 15
- 238000001556 precipitation Methods 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 239000012266 salt solution Substances 0.000 claims description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkali metal cation Chemical class 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- 239000012454 non-polar solvent Substances 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 238000005903 acid hydrolysis reaction Methods 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 150000002596 lactones Chemical class 0.000 abstract description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 239000000203 mixture Substances 0.000 description 22
- 239000010410 layer Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000000926 separation method Methods 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000126 substance Substances 0.000 description 8
- XQKKWWCELHKGKB-UHFFFAOYSA-L calcium acetate monohydrate Chemical compound O.[Ca+2].CC([O-])=O.CC([O-])=O XQKKWWCELHKGKB-UHFFFAOYSA-L 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229960005147 calcium acetate Drugs 0.000 description 4
- 239000001639 calcium acetate Substances 0.000 description 4
- 235000011092 calcium acetate Nutrition 0.000 description 4
- 239000002274 desiccant Substances 0.000 description 4
- 239000008241 heterogeneous mixture Substances 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 229940067460 calcium acetate monohydrate Drugs 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000008259 solid foam Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000640 hydroxylating effect Effects 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BJGBAZAEWKCPHZ-MQSFZEHASA-N (3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 BJGBAZAEWKCPHZ-MQSFZEHASA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Inorganic materials [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- AMJQWGIYCROUQF-UHFFFAOYSA-N calcium;methanolate Chemical compound [Ca+2].[O-]C.[O-]C AMJQWGIYCROUQF-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- VVRPOCPLIUDBSA-CNZCJKERSA-M sodium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical class [Na+].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 VVRPOCPLIUDBSA-CNZCJKERSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/04—Calcium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Способ получения аморфной формы гемикальциевой соли (3R,5R) 7-[3-фенил-4-фенилкарбамоил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидрогептановой кислоты формулы (І), в котором (3R,5R) 7-[3-фенил-4-фенилкарбамоил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидрогептановую кислоту или ее соль с катионом М+, где М+ является или катионом щелочного металла, или катионом аммония формулы RNN(+)Н(4-n), в которой R является низшим C1-C5 алкилом, n может достигать значений в промежутке 0 и 3, превращают, без отделения промежуточного соединения в форме гемикальциевой соли или другой соли, кислоты или лактона, в растворе путем обработки кальциевой солью или гидроксидом кальция, или алкоголятом C1-C5 кальция в гемикальциевую соль, которая осаждается углеводородом C1-C5, или диалкиловым этером формулы R1OR2, где каждый из R1 и R2 является C1-C5 алкильной группой. Исходную кислоту или ее соль получают реакцией, которая начинается из (3R,5R) трет-бутил (6-{2-(3-фенил-4-фенилкарбамоил 1-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-этил}-2,2-диметил-[1,3]диоксан-4-ил)-ацетата формулы II.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZ20020413A CZ296967B6 (cs) | 2002-02-01 | 2002-02-01 | Zpusob výroby amorfní formy hemivápenaté soli (3R,5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorfenyl)-5-isopropylpyrrol-1-yl]-3,5-dihydroxyheptanové kyseliny (atorvastatinu) |
| PCT/CZ2003/000007 WO2003068739A1 (en) | 2002-02-01 | 2003-01-30 | Method of manufacturing an amorphous form of the hemi-calcium salt of (3r, 5r) 7- 3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl!-3, 5-dihydroxyheptanoic acid (atorvastatin) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA76826C2 true UA76826C2 (ru) | 2006-09-15 |
Family
ID=27674298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20040907211A UA76826C2 (ru) | 2002-02-01 | 2003-01-30 | Способ получения аморфной формы гемикальциевой соли (3r,5r) 7-[3-фенил-4-фенилкарбамоил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидрогептановой кислоты (аторвастатина) |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7208608B2 (ru) |
| EP (1) | EP1470106B1 (ru) |
| JP (1) | JP2005521685A (ru) |
| KR (1) | KR20040081172A (ru) |
| AT (1) | ATE480516T1 (ru) |
| AU (1) | AU2003213986A1 (ru) |
| CZ (1) | CZ296967B6 (ru) |
| DE (1) | DE60334068D1 (ru) |
| EA (1) | EA007432B1 (ru) |
| ES (1) | ES2347324T3 (ru) |
| HU (1) | HUP0402590A3 (ru) |
| PL (1) | PL209756B1 (ru) |
| PT (1) | PT1470106E (ru) |
| UA (1) | UA76826C2 (ru) |
| WO (1) | WO2003068739A1 (ru) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011088806A2 (en) | 2010-01-19 | 2011-07-28 | Zentiva, K.S. | A method of industrial production of an amorphous form of atorvastatin with a high specific surface area and its use in a dosage form |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8367848B2 (en) * | 2003-04-11 | 2013-02-05 | Lek Pharmaceuticals D.D. | Process for the preparation of amorphous calcium salt of atorvastatin |
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-
2002
- 2002-02-01 CZ CZ20020413A patent/CZ296967B6/cs not_active IP Right Cessation
-
2003
- 2003-01-30 UA UA20040907211A patent/UA76826C2/ru unknown
- 2003-01-30 JP JP2003567871A patent/JP2005521685A/ja active Pending
- 2003-01-30 WO PCT/CZ2003/000007 patent/WO2003068739A1/en active Application Filing
- 2003-01-30 EA EA200400977A patent/EA007432B1/ru not_active IP Right Cessation
- 2003-01-30 US US10/502,632 patent/US7208608B2/en not_active Expired - Lifetime
- 2003-01-30 ES ES03709588T patent/ES2347324T3/es not_active Expired - Lifetime
- 2003-01-30 KR KR10-2004-7011960A patent/KR20040081172A/ko not_active Application Discontinuation
- 2003-01-30 PL PL370495A patent/PL209756B1/pl not_active IP Right Cessation
- 2003-01-30 HU HU0402590A patent/HUP0402590A3/hu unknown
- 2003-01-30 PT PT03709588T patent/PT1470106E/pt unknown
- 2003-01-30 AT AT03709588T patent/ATE480516T1/de not_active IP Right Cessation
- 2003-01-30 DE DE60334068T patent/DE60334068D1/de not_active Expired - Lifetime
- 2003-01-30 AU AU2003213986A patent/AU2003213986A1/en not_active Abandoned
- 2003-01-30 EP EP03709588A patent/EP1470106B1/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011088806A2 (en) | 2010-01-19 | 2011-07-28 | Zentiva, K.S. | A method of industrial production of an amorphous form of atorvastatin with a high specific surface area and its use in a dosage form |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003213986A1 (en) | 2003-09-04 |
| ATE480516T1 (de) | 2010-09-15 |
| ES2347324T3 (es) | 2010-10-28 |
| US7208608B2 (en) | 2007-04-24 |
| CZ296967B6 (cs) | 2006-08-16 |
| HUP0402590A2 (hu) | 2005-03-29 |
| PT1470106E (pt) | 2010-09-23 |
| EP1470106B1 (en) | 2010-09-08 |
| HUP0402590A3 (en) | 2010-06-28 |
| US20050131055A1 (en) | 2005-06-16 |
| WO2003068739A1 (en) | 2003-08-21 |
| PL370495A1 (en) | 2005-05-30 |
| DE60334068D1 (de) | 2010-10-21 |
| EP1470106A1 (en) | 2004-10-27 |
| EA007432B1 (ru) | 2006-10-27 |
| CZ2002413A3 (cs) | 2003-10-15 |
| JP2005521685A (ja) | 2005-07-21 |
| EA200400977A1 (ru) | 2004-12-30 |
| PL209756B1 (pl) | 2011-10-31 |
| KR20040081172A (ko) | 2004-09-20 |
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