HRP20030454A2 - Hydrolysis of [r(r*,r*)]-2-(4-fluorophenyl)-(3,6-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid esters with calcium hydroxide - Google Patents
Hydrolysis of [r(r*,r*)]-2-(4-fluorophenyl)-(3,6-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid esters with calcium hydroxide Download PDFInfo
- Publication number
- HRP20030454A2 HRP20030454A2 HR20030454A HRP20030454A HRP20030454A2 HR P20030454 A2 HRP20030454 A2 HR P20030454A2 HR 20030454 A HR20030454 A HR 20030454A HR P20030454 A HRP20030454 A HR P20030454A HR P20030454 A2 HRP20030454 A2 HR P20030454A2
- Authority
- HR
- Croatia
- Prior art keywords
- atorvastatin
- calcium
- ester derivative
- calcium hydroxide
- hemi
- Prior art date
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 title claims abstract description 58
- 239000000920 calcium hydroxide Substances 0.000 title claims abstract description 57
- 229910001861 calcium hydroxide Inorganic materials 0.000 title claims abstract description 57
- 238000006460 hydrolysis reaction Methods 0.000 title abstract description 38
- 230000007062 hydrolysis Effects 0.000 title abstract description 34
- 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 claims abstract description 93
- 229960005370 atorvastatin Drugs 0.000 claims abstract description 93
- -1 atorvastatin ester Chemical class 0.000 claims abstract description 72
- 238000000034 method Methods 0.000 claims abstract description 71
- 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 claims abstract description 68
- 230000008569 process Effects 0.000 claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 47
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 39
- 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 claims description 24
- 239000002253 acid Substances 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 239000012046 mixed solvent Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000001556 precipitation Methods 0.000 claims description 11
- 230000007704 transition Effects 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000003377 acid catalyst Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- UDYGXWPMSJPFDG-UHFFFAOYSA-M benzyl(tributyl)azanium;bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 UDYGXWPMSJPFDG-UHFFFAOYSA-M 0.000 claims 1
- CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 18
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000005580 one pot reaction Methods 0.000 abstract description 8
- 238000005903 acid hydrolysis reaction Methods 0.000 abstract description 6
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002243 precursor Substances 0.000 abstract description 2
- PDBMVYIMAMQDCW-UHFFFAOYSA-N 3,5-dihydroxyheptanoic acid Chemical compound CCC(O)CC(O)CC(O)=O PDBMVYIMAMQDCW-UHFFFAOYSA-N 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- 235000011116 calcium hydroxide Nutrition 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 235000019441 ethanol Nutrition 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 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 description 13
- 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 12
- 150000002596 lactones Chemical class 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000010533 azeotropic distillation Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229960002713 calcium chloride Drugs 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 238000006086 Paal-Knorr synthesis reaction Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229910001424 calcium ion Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000000532 dioxanyl group Chemical group 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical group C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 2
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 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 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 229940102001 zinc bromide Drugs 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-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical group CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
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- 229960005069 calcium Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
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- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
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- 125000005594 diketone group Chemical group 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
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- 239000012065 filter cake Substances 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical group O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- 150000001261 hydroxy acids Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000007273 lactonization reaction Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical group 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Classifications
-
- 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/06—Potassium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
- C07D209/24—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 with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—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
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular 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)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24931900P | 2000-11-16 | 2000-11-16 | |
| US31214401P | 2001-08-13 | 2001-08-13 | |
| US32652901P | 2001-10-01 | 2001-10-01 | |
| PCT/US2001/050639 WO2002043667A2 (en) | 2000-11-16 | 2001-10-24 | HYDROLYSIS OF [R(R*,R*)]-2-(4-FLUOROPHENYL)-β,δ -DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID ESTERS WITH CALCIUM HYDROXIDE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20030454A2 true HRP20030454A2 (en) | 2005-10-31 |
Family
ID=27400196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20030454A HRP20030454A2 (en) | 2000-11-16 | 2003-06-05 | Hydrolysis of [r(r*,r*)]-2-(4-fluorophenyl)-(3,6-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid esters with calcium hydroxide |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6528661B2 (xx) |
| EP (1) | EP1341785B1 (xx) |
| JP (1) | JP4234429B2 (xx) |
| KR (1) | KR100877165B1 (xx) |
| CN (1) | CN1330644C (xx) |
| AT (1) | ATE410413T1 (xx) |
| AU (2) | AU3289102A (xx) |
| CA (1) | CA2427255A1 (xx) |
| CZ (1) | CZ20031595A3 (xx) |
| DE (1) | DE60136095D1 (xx) |
| DK (1) | DK1341785T3 (xx) |
| ES (1) | ES2313999T3 (xx) |
| HR (1) | HRP20030454A2 (xx) |
| HU (1) | HUP0303555A3 (xx) |
| IL (1) | IL155890A0 (xx) |
| IS (1) | IS6814A (xx) |
| MX (1) | MXPA03004276A (xx) |
| NO (1) | NO20032200L (xx) |
| NZ (1) | NZ526022A (xx) |
| PL (1) | PL362981A1 (xx) |
| PT (1) | PT1341785E (xx) |
| SK (1) | SK7212003A3 (xx) |
| WO (1) | WO2002043667A2 (xx) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7411075B1 (en) | 2000-11-16 | 2008-08-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic form of atorvastatin calcium |
| 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 |
| WO2002057229A1 (en) * | 2001-01-19 | 2002-07-25 | Biocon India Limited | FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN) |
| EA005317B1 (ru) * | 2001-06-29 | 2004-12-30 | УОРНЕР-ЛАМБЕРТ КОМПАНИ Эл-Эл-Си | Кристаллические формы [r-(r*,r*)]-2-(4-фторфенил)-бета, дельта-дигидрокси-5-(1-метилэтил)-3-фенил-4-[(фениламино)карбонил]-1h-пиррол-1-гептановой кислоты кальциевой соли (2:1) (аторвастатин) |
| US7074818B2 (en) * | 2001-07-30 | 2006-07-11 | Dr. Reddy's Laboratories Limited | Crystalline forms VI and VII of Atorvastatin calcium |
| EP1414796A1 (en) * | 2001-07-30 | 2004-05-06 | Dr. Reddy's Laboratories Ltd. | Crystalline forms vi and vii of atorvastatin calcium |
| US7361772B2 (en) * | 2001-08-16 | 2008-04-22 | Biocon Limited | Process for the production of atorvastatin calcium |
| TR200302281T2 (tr) * | 2001-08-16 | 2004-09-21 | Teva Pharmaceutical Industries Ltd. | Statinlerin kalsiyum tuzu formlarını hazırlamak için işlemler |
| US7563911B2 (en) * | 2001-08-31 | 2009-07-21 | Morepen Laboratories Ltd. | Process for the preparation of amorphous atorvastin calcium salt (2:1) |
| US20060020137A1 (en) * | 2001-11-29 | 2006-01-26 | Limor Tessler | Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms |
| JP4524111B2 (ja) * | 2002-01-31 | 2010-08-11 | ノバルティス アーゲー | ＨＭＧ−ＣｏＡ還元酵素阻害剤の製造法 |
| ATE452871T1 (de) | 2002-03-18 | 2010-01-15 | Biocon Ltd | Amorphe hmg-coa-reduktase-inhibitoren mit gewünschter teilchengrösse |
| US7179942B2 (en) * | 2002-07-05 | 2007-02-20 | Bicon Limited | Halo-substituted active methylene compounds |
| GB0218781D0 (en) | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| WO2004072040A1 (en) | 2003-02-12 | 2004-08-26 | Ciba Specialty Chemicals Holding Inc. | Crystalline forms of pitavastatin calcium |
| SI1631533T1 (sl) | 2003-04-22 | 2009-08-31 | Bicon Ltd | Nov postopek za stereoselektivno redukcijo beta - ketoestrov |
| GB0312896D0 (en) | 2003-06-05 | 2003-07-09 | Astrazeneca Ab | Chemical process |
| US7790197B2 (en) | 2003-06-09 | 2010-09-07 | Warner-Lambert Company Llc | Pharmaceutical compositions of atorvastatin |
| US20050271717A1 (en) | 2003-06-12 | 2005-12-08 | Alfred Berchielli | Pharmaceutical compositions of atorvastatin |
| US7655692B2 (en) | 2003-06-12 | 2010-02-02 | Pfizer Inc. | Process for forming amorphous atorvastatin |
| UY28501A1 (es) | 2003-09-10 | 2005-04-29 | Astrazeneca Uk Ltd | Compuestos químicos |
| AU2004272365A1 (en) * | 2003-09-17 | 2005-03-24 | Warner-Lambert Company Llc | Crystalline forms of `R-(R*,R*))-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-`(phenylamino)carbonyl!-1H-pyrrole-1-heptanoic acid |
| AU2003272080A1 (en) | 2003-09-18 | 2005-04-06 | Biocon Limited | Novel process for the preparation of tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate |
| GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
| CA2551549A1 (en) * | 2003-12-29 | 2005-07-14 | Lek Pharmaceuticals D.D. | Process for preparing amorphous (4r-cis)-6-[2-[3-phenyl-4-(phenylcarbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-pyrrol-1-yl]-ethyl]-2,2-dimethyl-[1,3]-dioxane-4-yl-acetic acid |
| SI21745A (sl) * | 2004-04-09 | 2005-10-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Polimorfi derivata 1-pirol-1-heptanojske kisline, intermediata za pripravo atorvastatina |
| ES2739493T3 (es) | 2004-05-05 | 2020-01-31 | Pfizer Prod Inc | Formas de sal de de atorvastatina con benetamina |
| JP5000502B2 (ja) * | 2004-07-16 | 2012-08-15 | レツク・フアーマシユーテイカルズ・デー・デー | アトルバスタチンカルシウムの酸化分解生成物 |
| CA2672554C (en) | 2004-07-20 | 2012-01-03 | Warner-Lambert Company Llc | Novel forms of [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) |
| AU2005298383A1 (en) | 2004-10-28 | 2006-05-04 | Warner-Lambert Company Llc | Process for forming amorphous atorvastatin |
| CA2499047A1 (en) * | 2005-03-01 | 2006-09-01 | Apotex Pharmachem Inc. | Process for producing atorvastatin hemicalcium |
| CA2601111A1 (en) * | 2005-03-14 | 2006-09-21 | Pfizer Science And Technology Ireland Limited | Preparation of an atorvastatin intermediate using a paal-knorr condensation |
| US20090221852A1 (en) * | 2005-09-09 | 2009-09-03 | Pfizer Inc. | Preparation of an Atorvastatin Intermediate |
| DE602005014686D1 (de) * | 2005-09-09 | 2009-07-09 | Pfizer Science & Tech Ltd | Herstellung eines atorvastatin-zwischenprodukts |
| CA2547216A1 (en) | 2005-09-21 | 2007-03-21 | Renuka D. Reddy | Process for annealing amorphous atorvastatin |
| DE602006014193D1 (de) | 2005-11-21 | 2010-06-17 | Warner Lambert Co | Neue formen von är-(r*,r*)ü-2-(4-fluorphenyl)-b,d-dihydroxy-5-(1-methylethyl)-3-phenyl-4-ä(phenylamino)carbonylü-1h-pyrrol-1-heptansäure-magnesium |
| BRPI0610344A2 (pt) * | 2005-12-13 | 2016-11-29 | Teva Pharma | forma cristalizada do atorvastatin hemi-calcium, processo para sua preparação, produto famacêutico derivado e seu uso medicinal |
| EP1877375A1 (en) * | 2006-03-01 | 2008-01-16 | Teva Pharmaceutical Industries Ltd | Process for preparing a crystalline form of atorvastatin hemi-calcium |
| WO2009082362A1 (en) * | 2007-11-05 | 2009-07-02 | Ulkar Kimya San. Ve Tic. A.S. | A method for producing statins in pure form |
| KR100850850B1 (ko) * | 2008-01-25 | 2008-08-06 | 주식회사종근당 | 아토르바스타틴의 제조방법 및 이에 사용되는 중간체 |
| US11473032B2 (en) | 2010-02-02 | 2022-10-18 | Fuchs Petrolub Se | Constant velocity joint having a boot |
| CN102858740B (zh) * | 2010-04-19 | 2015-10-21 | 中化帝斯曼制药有限公司荷兰公司 | 低内酯杂质的阿托伐他汀的制备 |
| WO2011131605A1 (en) * | 2010-04-19 | 2011-10-27 | Dsm Ip Assets B.V. | Production of atorvastatin low in ether impurities |
| JP5843406B2 (ja) | 2014-02-19 | 2016-01-13 | 株式会社オートネットワーク技術研究所 | 金属表面コーティング用組成物およびこれを用いた端子付き被覆電線 |
| CN104447487A (zh) * | 2014-12-07 | 2015-03-25 | 河南豫辰药业股份有限公司 | 一种阿托伐他汀半钙的制备方法 |
| JP6830051B2 (ja) * | 2017-10-11 | 2021-02-17 | 東レ・ファインケミカル株式会社 | 高純度トリフルオロメチル基置換芳香族ケトンの製造方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4137322A (en) * | 1976-11-02 | 1979-01-30 | Sankyo Company Limited | ML-236B carboxylic acid derivatives and their use as antihyperlipemic agents |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| HRP960312B1 (en) * | 1995-07-17 | 2001-10-31 | Warner Lambert Co | NOVEL PROCESS FOR THE PRODUCTION OF AMORPHOUS /R-(R*, R*)/-2-(4-FLUOROPHENYL)-"beta", "delta"-DIHYDROXY-5-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 |
| TR200302281T2 (tr) * | 2001-08-16 | 2004-09-21 | Teva Pharmaceutical Industries Ltd. | Statinlerin kalsiyum tuzu formlarını hazırlamak için işlemler |
-
2001
- 2001-10-24 AU AU3289102A patent/AU3289102A/xx active Pending
- 2001-10-24 KR KR1020037006582A patent/KR100877165B1/ko not_active IP Right Cessation
- 2001-10-24 SK SK721-2003A patent/SK7212003A3/sk not_active Application Discontinuation
- 2001-10-24 PL PL01362981A patent/PL362981A1/xx not_active Application Discontinuation
- 2001-10-24 HU HU0303555A patent/HUP0303555A3/hu unknown
- 2001-10-24 AU AU2002232891A patent/AU2002232891B2/en not_active Ceased
- 2001-10-24 AT AT01992422T patent/ATE410413T1/de not_active IP Right Cessation
- 2001-10-24 WO PCT/US2001/050639 patent/WO2002043667A2/en active IP Right Grant
- 2001-10-24 CN CNB018219683A patent/CN1330644C/zh not_active Expired - Fee Related
- 2001-10-24 ES ES01992422T patent/ES2313999T3/es not_active Expired - Lifetime
- 2001-10-24 IL IL15589001A patent/IL155890A0/xx unknown
- 2001-10-24 MX MXPA03004276A patent/MXPA03004276A/es active IP Right Grant
- 2001-10-24 EP EP01992422A patent/EP1341785B1/en not_active Expired - Lifetime
- 2001-10-24 US US10/037,412 patent/US6528661B2/en not_active Expired - Fee Related
- 2001-10-24 CA CA002427255A patent/CA2427255A1/en not_active Withdrawn
- 2001-10-24 PT PT01992422T patent/PT1341785E/pt unknown
- 2001-10-24 DE DE60136095T patent/DE60136095D1/de not_active Expired - Lifetime
- 2001-10-24 CZ CZ20031595A patent/CZ20031595A3/cs unknown
- 2001-10-24 NZ NZ526022A patent/NZ526022A/en unknown
- 2001-10-24 DK DK01992422T patent/DK1341785T3/da active
- 2001-10-24 JP JP2002545646A patent/JP4234429B2/ja not_active Expired - Fee Related
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2003
- 2003-05-14 IS IS6814A patent/IS6814A/is unknown
- 2003-05-15 NO NO20032200A patent/NO20032200L/no not_active Application Discontinuation
- 2003-06-05 HR HR20030454A patent/HRP20030454A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002232891B2 (en) | 2006-12-14 |
| KR100877165B1 (ko) | 2009-01-07 |
| CA2427255A1 (en) | 2002-06-06 |
| AU3289102A (en) | 2002-06-11 |
| JP4234429B2 (ja) | 2009-03-04 |
| KR20030059253A (ko) | 2003-07-07 |
| JP2004514687A (ja) | 2004-05-20 |
| SK7212003A3 (en) | 2004-03-02 |
| EP1341785A2 (en) | 2003-09-10 |
| ATE410413T1 (de) | 2008-10-15 |
| ES2313999T3 (es) | 2009-03-16 |
| EP1341785A4 (en) | 2004-05-12 |
| EP1341785B1 (en) | 2008-10-08 |
| MXPA03004276A (es) | 2005-04-29 |
| PT1341785E (pt) | 2009-01-16 |
| CN1330644C (zh) | 2007-08-08 |
| US6528661B2 (en) | 2003-03-04 |
| HUP0303555A2 (hu) | 2004-03-01 |
| WO2002043667A2 (en) | 2002-06-06 |
| DK1341785T3 (da) | 2009-01-26 |
| PL362981A1 (en) | 2004-11-02 |
| CN1561341A (zh) | 2005-01-05 |
| NZ526022A (en) | 2005-04-29 |
| CZ20031595A3 (cs) | 2003-11-12 |
| HUP0303555A3 (en) | 2005-08-29 |
| IS6814A (is) | 2003-05-14 |
| US20020099224A1 (en) | 2002-07-25 |
| DE60136095D1 (de) | 2008-11-20 |
| IL155890A0 (en) | 2003-12-23 |
| NO20032200L (no) | 2003-06-24 |
| NO20032200D0 (no) | 2003-05-15 |
| WO2002043667A3 (en) | 2002-10-10 |
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