ES2339570T3 - Polimorfos de ester terc-butilo de la atorvastatina y su utilizacion como intermediarios para la preparacion de la atorvastatina. - Google Patents
Polimorfos de ester terc-butilo de la atorvastatina y su utilizacion como intermediarios para la preparacion de la atorvastatina. Download PDFInfo
- Publication number
- ES2339570T3 ES2339570T3 ES05729986T ES05729986T ES2339570T3 ES 2339570 T3 ES2339570 T3 ES 2339570T3 ES 05729986 T ES05729986 T ES 05729986T ES 05729986 T ES05729986 T ES 05729986T ES 2339570 T3 ES2339570 T3 ES 2339570T3
- Authority
- ES
- Spain
- Prior art keywords
- atorvastatin
- tert
- water
- butyl
- ester
- 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
- 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 81
- 229960005370 atorvastatin Drugs 0.000 title claims description 81
- 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 description 64
- 238000002360 preparation method Methods 0.000 title claims description 33
- 150000002148 esters Chemical class 0.000 title claims description 7
- GCPKKGVOCBYRML-LOYHVIPDSA-N tert-butyl (3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate 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)OC(C)(C)C)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 GCPKKGVOCBYRML-LOYHVIPDSA-N 0.000 claims abstract description 38
- 238000002441 X-ray diffraction Methods 0.000 claims abstract description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 31
- 239000011541 reaction mixture Substances 0.000 claims description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 238000001938 differential scanning calorimetry curve Methods 0.000 claims description 7
- OUCSEDFVYPBLLF-KAYWLYCHSA-N 5-(4-fluorophenyl)-1-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-n,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 OUCSEDFVYPBLLF-KAYWLYCHSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- -1 for example Chemical compound 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 239000011260 aqueous acid Substances 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 8
- 239000001110 calcium chloride Substances 0.000 description 8
- 229910001628 calcium chloride Inorganic materials 0.000 description 8
- 235000011148 calcium chloride Nutrition 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- BNGGGQKEDABCQY-HTQZYQBOSA-N 2-[(4r,6r)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid Chemical compound CC1(C)O[C@H](CCN)C[C@H](CC(O)=O)O1 BNGGGQKEDABCQY-HTQZYQBOSA-N 0.000 description 4
- 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 4
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000008241 heterogeneous mixture Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 238000000935 solvent evaporation Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 2
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- UAXOELSVPTZZQG-UHFFFAOYSA-N tiglic acid Natural products CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- YFMKJVDVNPLQFO-FQLXRVMXSA-N 2-[(4r,6r)-6-[2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(C)(C)O[C@@H](CC(O)=O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 YFMKJVDVNPLQFO-FQLXRVMXSA-N 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- PUYCICVJCRLABY-UHFFFAOYSA-N heptane;oxolane Chemical compound C1CCOC1.CCCCCCC PUYCICVJCRLABY-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- C07D207/34—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI200400112 | 2004-04-09 | ||
| SI200400112A SI21745A (sl) | 2004-04-09 | 2004-04-09 | Polimorfi derivata 1-pirol-1-heptanojske kisline, intermediata za pripravo atorvastatina |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2339570T3 true ES2339570T3 (es) | 2010-05-21 |
Family
ID=34963800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05729986T Expired - Lifetime ES2339570T3 (es) | 2004-04-09 | 2005-04-08 | Polimorfos de ester terc-butilo de la atorvastatina y su utilizacion como intermediarios para la preparacion de la atorvastatina. |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1732886B1 (e) |
| CN (2) | CN101538238B (e) |
| AT (1) | ATE459602T1 (e) |
| DE (1) | DE602005019703D1 (e) |
| DK (1) | DK1732886T3 (e) |
| EA (1) | EA010166B1 (e) |
| ES (1) | ES2339570T3 (e) |
| HR (1) | HRP20100217T1 (e) |
| NO (1) | NO20065146L (e) |
| PL (1) | PL1732886T3 (e) |
| PT (1) | PT1732886E (e) |
| RS (1) | RS51259B (e) |
| SI (2) | SI21745A (e) |
| UA (1) | UA86059C2 (e) |
| WO (1) | WO2005097742A1 (e) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006313430B2 (en) * | 2005-11-08 | 2012-09-06 | Ranbaxy Laboratories Limited | Process for (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- [(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt |
| US20100260851A1 (en) * | 2007-07-11 | 2010-10-14 | Actavis Group Ptc Ehf | Novel Polymorph of Atorvastatin Calcium and Use Thereof for the Preparation of Amorphous Atorvastatin Calcium |
| WO2009023260A2 (en) * | 2007-08-15 | 2009-02-19 | Teva Pharmaceutical Industries Ltd. | An improved process for synthesis of pyrrole derivative, an intermediate for atorvastatin |
| CN101560177B (zh) * | 2008-04-16 | 2012-10-03 | 北京万全阳光医学技术有限公司 | 一种阿托伐他汀钙的制备方法 |
| SI2413911T1 (sl) | 2009-03-31 | 2014-04-30 | Krka, D.D., Novo Mesto | Progresivna emulzijska kristalizacija |
| CN105693587A (zh) * | 2016-01-15 | 2016-06-22 | 安徽悦康凯悦制药有限公司 | 一种阿托伐他汀钙的生产工艺 |
| CN109280024A (zh) * | 2018-10-09 | 2019-01-29 | 河南师范大学 | 一种高纯度阿托伐他汀叔丁酯的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI94339C (fi) * | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| EP1341785B1 (en) * | 2000-11-16 | 2008-10-08 | Teva Pharmaceutical Industries Ltd. | Hydrolysis of r(r*,r*)-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4- [(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid esters with calcium hydroxide |
| US6476235B2 (en) * | 2001-01-09 | 2002-11-05 | Warner-Lambert Company | Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide |
| CN100430405C (zh) * | 2001-08-16 | 2008-11-05 | 特瓦制药工业有限公司 | 制备他汀类的钙盐形式的方法 |
-
2004
- 2004-04-09 SI SI200400112A patent/SI21745A/sl not_active IP Right Cessation
-
2005
- 2005-04-08 AT AT05729986T patent/ATE459602T1/de active
- 2005-04-08 CN CN2009101368132A patent/CN101538238B/zh not_active Expired - Fee Related
- 2005-04-08 CN CN200580012246XA patent/CN1946687B/zh not_active Expired - Fee Related
- 2005-04-08 WO PCT/EP2005/003733 patent/WO2005097742A1/en active Application Filing
- 2005-04-08 EA EA200601651A patent/EA010166B1/ru not_active IP Right Cessation
- 2005-04-08 DE DE602005019703T patent/DE602005019703D1/de not_active Expired - Lifetime
- 2005-04-08 PT PT05729986T patent/PT1732886E/pt unknown
- 2005-04-08 PL PL05729986T patent/PL1732886T3/pl unknown
- 2005-04-08 DK DK05729986.9T patent/DK1732886T3/da active
- 2005-04-08 RS RSP-2010/0173A patent/RS51259B/sr unknown
- 2005-04-08 EP EP05729986A patent/EP1732886B1/en not_active Expired - Lifetime
- 2005-04-08 HR HR20100217T patent/HRP20100217T1/hr unknown
- 2005-04-08 ES ES05729986T patent/ES2339570T3/es not_active Expired - Lifetime
- 2005-04-08 SI SI200531002T patent/SI1732886T1/sl unknown
- 2005-08-04 UA UAA200610957A patent/UA86059C2/ru unknown
-
2006
- 2006-11-08 NO NO20065146A patent/NO20065146L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE602005019703D1 (de) | 2010-04-15 |
| CN101538238B (zh) | 2012-08-29 |
| UA86059C2 (ru) | 2009-03-25 |
| EA200601651A1 (ru) | 2007-02-27 |
| RS51259B (sr) | 2010-12-31 |
| ATE459602T1 (de) | 2010-03-15 |
| DK1732886T3 (da) | 2010-06-14 |
| HRP20100217T1 (hr) | 2010-05-31 |
| WO2005097742A1 (en) | 2005-10-20 |
| CN1946687A (zh) | 2007-04-11 |
| EA010166B1 (ru) | 2008-06-30 |
| SI1732886T1 (sl) | 2010-06-30 |
| EP1732886A1 (en) | 2006-12-20 |
| PT1732886E (pt) | 2010-03-12 |
| CN1946687B (zh) | 2011-09-28 |
| EP1732886B1 (en) | 2010-03-03 |
| CN101538238A (zh) | 2009-09-23 |
| SI21745A (sl) | 2005-10-31 |
| NO20065146L (no) | 2006-11-08 |
| PL1732886T3 (pl) | 2010-08-31 |
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