CZ296967B6 - 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) - Google Patents
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) Download PDFInfo
- Publication number
- CZ296967B6 CZ296967B6 CZ20020413A CZ2002413A CZ296967B6 CZ 296967 B6 CZ296967 B6 CZ 296967B6 CZ 20020413 A CZ20020413 A CZ 20020413A CZ 2002413 A CZ2002413 A CZ 2002413A CZ 296967 B6 CZ296967 B6 CZ 296967B6
- Authority
- CZ
- Czechia
- Prior art keywords
- phenylcarbamoyl
- fluorophenyl
- phenyl
- solution
- salt
- Prior art date
Links
- 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 claims abstract description 54
- 150000003839 salts Chemical class 0.000 title claims abstract description 17
- 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 claims description 53
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- CLIROFKDXQCWFY-VSGBNLITSA-N (3R,5R)-7-[2-(4-fluorophenyl)-3-[(3-phenylphenyl)carbamoyl]-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C1(=CC=CC=C1)C=1C=C(C=CC=1)NC(=O)C1=C(N(C(=C1)C(C)C)CC[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F CLIROFKDXQCWFY-VSGBNLITSA-N 0.000 title abstract 2
- 229960005370 atorvastatin Drugs 0.000 title description 48
- 238000000034 method Methods 0.000 claims abstract description 34
- 239000002253 acid Substances 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 17
- 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
- 239000011575 calcium Substances 0.000 claims abstract description 7
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 6
- 150000001983 dialkylethers Chemical class 0.000 claims abstract description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 5
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 5
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 5
- 230000020477 pH reduction Effects 0.000 claims abstract description 5
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 97
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 66
- 239000000243 solution Substances 0.000 claims description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 238000001556 precipitation Methods 0.000 claims description 12
- 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
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 4
- 239000012454 non-polar solvent Substances 0.000 claims description 4
- 239000012266 salt solution Substances 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
- PDBMVYIMAMQDCW-UHFFFAOYSA-N 3,5-dihydroxyheptanoic acid Chemical compound CCC(O)CC(O)CC(O)=O PDBMVYIMAMQDCW-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 7
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- NPPZOMYSGNZDKY-UHFFFAOYSA-N tert-butyl 2-[6-[2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC2OC(C)(C)OC(CC(=O)OC(C)(C)C)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 NPPZOMYSGNZDKY-UHFFFAOYSA-N 0.000 abstract description 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 5
- 239000003513 alkali Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 238000011403 purification operation Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 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 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- XQKKWWCELHKGKB-UHFFFAOYSA-L calcium acetate monohydrate Chemical compound O.[Ca+2].CC([O-])=O.CC([O-])=O XQKKWWCELHKGKB-UHFFFAOYSA-L 0.000 description 8
- 238000000926 separation method Methods 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].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 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 5
- 229960005147 calcium acetate Drugs 0.000 description 5
- 239000001639 calcium acetate Substances 0.000 description 5
- 235000011092 calcium acetate Nutrition 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000002274 desiccant Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000008241 heterogeneous mixture Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- 229940067460 calcium acetate monohydrate Drugs 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- VVRPOCPLIUDBSA-CNZCJKERSA-M sodium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical compound [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 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000008259 solid foam 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 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
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000006260 foam Substances 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
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 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)
Priority Applications (15)
| 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) |
| HU0402590A HUP0402590A3 (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-phenylcarbomoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl!-3, 5-dihydroxyheptanoic acid (atorvastatin) |
| AU2003213986A AU2003213986A1 (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) |
| EP03709588A EP1470106B1 (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) |
| EA200400977A EA007432B1 (ru) | 2002-02-01 | 2003-01-30 | Способ получения аморфной формы полукальциевой соли (3r,5r)-7-[3-фенил-4-фенилкарбамил-2-(4-фторфенил)-5-изопропилпиррол-1-ил]-3,5-дигидроксигептановой кислоты (аторвастатина) |
| PL370495A PL209756B1 (pl) | 2002-02-01 | 2003-01-30 | Sposób wytwarzania amorficznej postaci soli hemiwapniowej kwasu (3R,5R) 7-[3-fenylo-4-fenylokarbamoilo-2-(4-fluorofenylo)-5-izopropylopirol-1-ilo]-3,5-dihydroksyheptanowego (atorwastatyny) |
| UA20040907211A UA76826C2 (uk) | 2002-02-01 | 2003-01-30 | Спосіб одержання аморфної форми гемікальцієвої солі (3r,5r) 7-[3-феніл-4-фенілкарбамоїл-2-(4-фторфеніл)-5-ізопропілпірол-1-іл]-3,5-дигідрогептанової кислоти (аторвастатину) |
| ES03709588T ES2347324T3 (es) | 2002-02-01 | 2003-01-30 | Metodo de fabricacion de un forma amorfa de sal semicalcica del acido (3r,5r)7-3-fenil-4-fenilcarbamoil-2-(4-fluorofenil)-5-isopropil-pirroll-1-il)-3,5-dihidroxiheptanoico (atorvastatina). |
| JP2003567871A JP2005521685A (ja) | 2002-02-01 | 2003-01-30 | （３ｒ，５ｒ）７−［３−フェニル−４−フェニルカルバモイル−２−（４−フルオロフェニル）−５−イソプロピル−ピロール−１−イル］−３，５−ジヒドロキシヘプタン酸のヘミ−カルシウム塩（アトロバスタチン）の非晶質形を製造する方法 |
| AT03709588T ATE480516T1 (de) | 2002-02-01 | 2003-01-30 | Verfahren zur herstellung einer amorphen form des hemicalciumsalzes von (3r, 5r)-7-c3-phenyl-4- phenyl carbamoyl-2-(4-fluorphenyl)-5-isopropyl pyrrol-1-ylü-3,5-dihydroxy heptan säure (atorvastatin) |
| 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) |
| PT03709588T PT1470106E (pt) | 2002-02-01 | 2003-01-30 | Um método de fabricar uma forma amorfa do sal hemi-cálcico do ácido (3r,5r)-7-3-fenil-4-fenilcarbamoil-2-(4- fluorofenil)-5-isopropil-pirrol-1-il-3,5-di-hidroxiheptanóico (atorvastatina) |
| KR10-2004-7011960A KR20040081172A (ko) | 2002-02-01 | 2003-01-30 | (3알,5알)7-3-페닐-4-페닐카바모일-2-(4-플로로페닐)-5-이소프로필-피롤-1-일!-3,5-디하이드록시헵타노익산(아토르바스타틴)의 반칼슘염의 무정형 제조 방법 |
| US10/502,632 US7208608B2 (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-yll-3, 5-dihydroxyheptanoic acid (actorvastatin) |
| DE60334068T DE60334068D1 (de) | 2002-02-01 | 2003-01-30 | VERFAHREN ZUR HERSTELLUNG EINER AMORPHEN FORM DES HEMICALCIUMSALZES VON (3R, 5R)-7-c3-PHENYL-4-PHENYL CARBAMOYL-2-(4-FLUORPHENYL)-5-ISOPROPYL PYRROL-1-YLÜ-3,5-DIHYDROXY HEPTAN SÄURE (ATORVASTATIN) |
Applications Claiming Priority (1)
| 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) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ2002413A3 CZ2002413A3 (cs) | 2003-10-15 |
| CZ296967B6 true CZ296967B6 (cs) | 2006-08-16 |
Family
ID=27674298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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) |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7208608B2 (enExample) |
| EP (1) | EP1470106B1 (enExample) |
| JP (1) | JP2005521685A (enExample) |
| KR (1) | KR20040081172A (enExample) |
| AT (1) | ATE480516T1 (enExample) |
| AU (1) | AU2003213986A1 (enExample) |
| CZ (1) | CZ296967B6 (enExample) |
| DE (1) | DE60334068D1 (enExample) |
| EA (1) | EA007432B1 (enExample) |
| ES (1) | ES2347324T3 (enExample) |
| HU (1) | HUP0402590A3 (enExample) |
| PL (1) | PL209756B1 (enExample) |
| PT (1) | PT1470106E (enExample) |
| UA (1) | UA76826C2 (enExample) |
| WO (1) | WO2003068739A1 (enExample) |
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 |
| AU2003247327A1 (en) * | 2003-07-15 | 2005-01-28 | Eos Eczacibasi Ozgun Kimyasal Urunler Sanyi Ve Ticaret A.S. | Process for the preparation of amortphous atorvastatin calcium without interconversion of any crystalline form |
| SI1727795T1 (sl) * | 2004-03-17 | 2012-05-31 | Ranbaxy Lab Ltd | Postopek za pripravo atorvastatin kalcija v amorfni obliki |
| RU2412191C2 (ru) * | 2004-07-16 | 2011-02-20 | Лек Фармасьютиклз Д.Д. | Продукты окислительной деструкции кальций аторвастатина |
| WO2006011155A1 (en) * | 2004-07-26 | 2006-02-02 | Apollo International Limited | One pot process for amorphous atorvastain calcium |
| JP2008510798A (ja) * | 2004-08-27 | 2008-04-10 | バイオコン・リミテッド | 非晶質アトルバスタチンカルシウムのための方法 |
| MX2007004425A (es) * | 2004-10-18 | 2007-06-07 | Teva Pharma | Proceso para preparar hemi-calcio de atorvastatina amorfo disolviendo la sal en un solvente organico que es una mezcla de un alcohol y una cetona y/o un ester y removiendo el solvente. |
| WO2006048893A2 (en) * | 2004-11-05 | 2006-05-11 | Morepen Laboratories Limited | A process for synthesis of large particle size statin compounds |
| CA2499047A1 (en) * | 2005-03-01 | 2006-09-01 | Apotex Pharmachem Inc. | Process for producing atorvastatin hemicalcium |
| GB2424880A (en) * | 2005-04-06 | 2006-10-11 | Generics | Crystalline forms of atorvastatin sodium, processes for their preparation and their use in inhibiting HMG-CoA reductase |
| WO2007020421A1 (en) | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| AU2006281229A1 (en) | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| ES2270722B1 (es) * | 2005-09-15 | 2008-03-01 | Ercros Industrial, S.A. | Procedimiento para la obtencion de atorvastatina calcica amorfa. |
| HU227696B1 (en) * | 2006-04-13 | 2011-12-28 | Egyt Gyogyszervegyeszeti Gyar | Zinc salt of rosuvastatin, process for its preparation and pharmaceutical compositions containing it |
| US20100113802A1 (en) * | 2006-11-02 | 2010-05-06 | Cadila Pharmaceuticals Limited | Process for preparing amorphous atorvastatin hemi calcium salt and its itermediate |
| KR100833439B1 (ko) * | 2007-01-02 | 2008-05-29 | 씨제이제일제당 (주) | 비결정형 아토르바스타틴 칼슘의 개선된 제조방법 |
| EP2075246A1 (en) | 2007-12-27 | 2009-07-01 | M. J. Institute of Research | A process for preparation of amorphous form of atorvastatin hemi-calcium salt |
| WO2009139730A1 (en) * | 2008-05-13 | 2009-11-19 | Ulkar Kimya San. Ve Tic. A.S. | Preparation of novel non-crystalline forms of atorvastatin calcium |
| KR101050722B1 (ko) * | 2008-12-02 | 2011-07-21 | 대웅바이오 주식회사 | 무정형 아토르바스타틴 칼슘염의 제조방법 |
| SI2373609T1 (sl) * | 2008-12-19 | 2013-12-31 | Krka, D.D., Novo Mesto | Uporaba amfifilnih spojin za kontrolirano kristalizacijo statinov in intermediatov statinov |
| EP2327682A1 (en) * | 2009-10-29 | 2011-06-01 | KRKA, D.D., Novo Mesto | Use of amphiphilic compounds for controlled crystallization of statins and statin intermediates |
| US8115015B2 (en) * | 2009-01-26 | 2012-02-14 | Cadila Healthcare Limited | Process for the preparation of amorphous atorvastatin calcium |
| HUE030160T2 (en) * | 2010-04-19 | 2017-05-29 | Dsm Sinochem Pharm Nl Bv | Preparation of atorvastatin with low dietary contamination |
| CN108774164A (zh) * | 2018-05-29 | 2018-11-09 | 宣城美诺华药业有限公司 | 一种阿托伐他汀钙合成方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4681893A (en) * | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| US5273995A (en) * | 1989-07-21 | 1993-12-28 | Warner-Lambert Company | [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino) carbonyl]- 1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof |
| EP0839132A1 (en) * | 1995-07-17 | 1998-05-06 | Warner-Lambert Company | Novel process for the production of amorphous [r-(r*,r*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
| EP0848704A1 (en) * | 1995-07-17 | 1998-06-24 | Warner-Lambert Company | Form iii crystalline [r-(r*,r*)]-2-(4-fluorophenyl)-beta-delta-dihydroxy-5-(1-methyl-ethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin) |
| WO2000071116A1 (en) * | 1999-05-25 | 2000-11-30 | Ranbaxy Laboratories Limited | Process for the production of amorphous atorvastatin calcium |
| SI20425A (sl) * | 1999-12-10 | 2001-06-30 | LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. | Priprava amorfnega atorvastatina |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5149837A (en) | 1988-02-22 | 1992-09-22 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5216174A (en) | 1988-02-22 | 1993-06-01 | Warner-Lambert Co. | Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5097045A (en) | 1989-02-01 | 1992-03-17 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5003080A (en) | 1988-02-22 | 1991-03-26 | Warner-Lambert Company | Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis |
| US5245047A (en) | 1988-02-22 | 1993-09-14 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5124482A (en) | 1988-02-22 | 1992-06-23 | Warner-Lambert Company | Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-2-one inhibitors of cholesterol synthesis |
| US5103024A (en) * | 1990-10-17 | 1992-04-07 | Warner-Lambert Company | Process for the synthesis of (4r-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
| US5248793A (en) | 1990-10-17 | 1993-09-28 | Warner-Lambert Company | Process for the synthesis of (4R-cis)-1,1-dimethylethyl 6-iodomethyl or 6-(phenyl-substituted)sulfonyloxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
| US5155251A (en) | 1991-10-11 | 1992-10-13 | Warner-Lambert Company | Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate |
| US5298627A (en) | 1993-03-03 | 1994-03-29 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| DE69634054T2 (de) | 1995-07-17 | 2005-12-08 | Warner-Lambert Co. | Kristalline (R-(R*, R*))-2-(4-Fluorophenyl)-β, δ-Dihydroxy-5-(1-Methylethyl)-3-Phenyl-4-((Phenylamino)Carbonyl)-1H-Pyrrol-1-Heptancarbonsäure Hemi Calcium Salz (Atorvastatin) |
| HRP960313B1 (en) | 1995-07-17 | 2002-08-31 | Warner Lambert Co | Form iii crystalline (r- (r*, r*)-2- (4-fluorophenyl) -beta-delta-hydroxy-5-(1-methylethyl) -3-phenyl-4- ((phenylamino) carbonyl -1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
| IL156055A0 (en) * | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
| US7501450B2 (en) * | 2000-11-30 | 2009-03-10 | Teva Pharaceutical Industries Ltd. | Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms |
| WO2002057228A1 (en) * | 2001-01-17 | 2002-07-25 | Biocon India Limited | Atorvastatin calcium |
| IN190564B (enExample) | 2001-04-11 | 2003-08-09 | Cadila Heathcare Ltd | |
| WO2003018547A2 (en) * | 2001-08-31 | 2003-03-06 | Morepen Laboratories Ltd. | An improved process for the preparation of amorphous atorvastatin calcium salt (2:1) |
-
2002
- 2002-02-01 CZ CZ20020413A patent/CZ296967B6/cs not_active IP Right Cessation
-
2003
- 2003-01-30 US US10/502,632 patent/US7208608B2/en not_active Expired - Lifetime
- 2003-01-30 AU AU2003213986A patent/AU2003213986A1/en not_active Abandoned
- 2003-01-30 WO PCT/CZ2003/000007 patent/WO2003068739A1/en not_active Ceased
- 2003-01-30 KR KR10-2004-7011960A patent/KR20040081172A/ko not_active Withdrawn
- 2003-01-30 HU HU0402590A patent/HUP0402590A3/hu unknown
- 2003-01-30 PL PL370495A patent/PL209756B1/pl not_active IP Right Cessation
- 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 ES ES03709588T patent/ES2347324T3/es not_active Expired - Lifetime
- 2003-01-30 EA EA200400977A patent/EA007432B1/ru not_active IP Right Cessation
- 2003-01-30 UA UA20040907211A patent/UA76826C2/uk unknown
- 2003-01-30 EP EP03709588A patent/EP1470106B1/en not_active Expired - Lifetime
- 2003-01-30 PT PT03709588T patent/PT1470106E/pt unknown
- 2003-01-30 JP JP2003567871A patent/JP2005521685A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4681893A (en) * | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| US5273995A (en) * | 1989-07-21 | 1993-12-28 | Warner-Lambert Company | [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino) carbonyl]- 1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof |
| EP0839132A1 (en) * | 1995-07-17 | 1998-05-06 | Warner-Lambert Company | Novel process for the production of amorphous [r-(r*,r*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
| EP0848704A1 (en) * | 1995-07-17 | 1998-06-24 | Warner-Lambert Company | Form iii crystalline [r-(r*,r*)]-2-(4-fluorophenyl)-beta-delta-dihydroxy-5-(1-methyl-ethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin) |
| WO2000071116A1 (en) * | 1999-05-25 | 2000-11-30 | Ranbaxy Laboratories Limited | Process for the production of amorphous atorvastatin calcium |
| SI20425A (sl) * | 1999-12-10 | 2001-06-30 | LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. | Priprava amorfnega atorvastatina |
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 |
|---|---|
| HUP0402590A2 (hu) | 2005-03-29 |
| HUP0402590A3 (en) | 2010-06-28 |
| US7208608B2 (en) | 2007-04-24 |
| PT1470106E (pt) | 2010-09-23 |
| CZ2002413A3 (cs) | 2003-10-15 |
| EP1470106B1 (en) | 2010-09-08 |
| EA200400977A1 (ru) | 2004-12-30 |
| ATE480516T1 (de) | 2010-09-15 |
| WO2003068739A1 (en) | 2003-08-21 |
| KR20040081172A (ko) | 2004-09-20 |
| UA76826C2 (uk) | 2006-09-15 |
| PL370495A1 (en) | 2005-05-30 |
| US20050131055A1 (en) | 2005-06-16 |
| AU2003213986A1 (en) | 2003-09-04 |
| JP2005521685A (ja) | 2005-07-21 |
| ES2347324T3 (es) | 2010-10-28 |
| EA007432B1 (ru) | 2006-10-27 |
| EP1470106A1 (en) | 2004-10-27 |
| DE60334068D1 (de) | 2010-10-21 |
| PL209756B1 (pl) | 2011-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ296967B6 (cs) | 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) | |
| RU2247113C2 (ru) | Способ получения аморфного аторвастатина | |
| CZ299215B6 (cs) | Zpusob výroby hemivápenaté soli (E)-7-[4-(4-fluorofenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxy-6-heptenovékyseliny | |
| CZ20032019A3 (cs) | Krystalické formy Atorvastatinu | |
| AU2001284385A8 (en) | An improved process for the preparation of amorphous atorvastatin calcium salt (2:1) | |
| EP1704144B1 (en) | A method of preparation of the hemi-calcium salt of (e)-7- [4-(4-fluorophenyl)-6-isopropyl-2- [me thyl(methylsulfonyl)amino]pyrimidin-5-yl](3r,5s)-3,5-dihydroxy-6-heptenoic acid | |
| EA013500B1 (ru) | Способ получения аморфной кальциевой соли аторвастатина | |
| EP1879862A2 (en) | Magnesium salts of hmg-coa reductase inhibitors | |
| US7615647B2 (en) | Process for producing atorvastatin hemicalcium | |
| RU2707043C1 (ru) | Способ получения гербицида имазамокса | |
| EP1979313A1 (en) | Process for the preparation of amorphous atorvastatin calcium salt | |
| US20040242670A1 (en) | Process for preparation of amorphous atorvastatin calcium | |
| CZ200594A3 (cs) | Zpusob výroby amorfní formy atorvastatinu | |
| KR101050722B1 (ko) | 무정형 아토르바스타틴 칼슘염의 제조방법 | |
| EA039290B1 (ru) | Способ выделения и очистки налтрексона | |
| US20050165242A1 (en) | Process for the preparation of amorphous atorvastatin calcium | |
| WO2005033078A1 (en) | Process for the production of atorvastatin calcium | |
| CZ2005573A3 (cs) | Zpusob výroby krystalické formy hemivápenaté soli(3R, 5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorofenyl)-5-isopropylpyrrol-1-y-1]-3,5 dihydroxyheptanové kyseliny (atorvastatinu) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20160201 |