US20030176706A1 - Process for the preparation of [S(-) amlodipine - L (+)- hemitartarate] - Google Patents
Process for the preparation of [S(-) amlodipine - L (+)- hemitartarate] Download PDFInfo
- Publication number
- US20030176706A1 US20030176706A1 US10/098,502 US9850202A US2003176706A1 US 20030176706 A1 US20030176706 A1 US 20030176706A1 US 9850202 A US9850202 A US 9850202A US 2003176706 A1 US2003176706 A1 US 2003176706A1
- Authority
- US
- United States
- Prior art keywords
- amlodipine
- hemi
- tartarate
- solid
- dmso
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 229960000528 amlodipine Drugs 0.000 title claims description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 64
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims abstract description 20
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 14
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims abstract description 9
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000011002 L(+)-tartaric acid Nutrition 0.000 claims abstract description 8
- 239000001358 L(+)-tartaric acid Substances 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 37
- 239000007787 solid Substances 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 12
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000010899 nucleation Methods 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000004296 chiral HPLC Methods 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- -1 amlodipine azide ester Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- JDTUPLBMGDDPJS-UHFFFAOYSA-N 2-methoxy-2-phenylethanol Chemical compound COC(CO)C1=CC=CC=C1 JDTUPLBMGDDPJS-UHFFFAOYSA-N 0.000 description 2
- ZURRKVIQUKNLHF-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[2.2.1]heptane-3-carboxylic acid Chemical compound C1CC2(C)C(C(O)=O)CC1C2(C)C ZURRKVIQUKNLHF-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- HTIQEAQVCYTUBX-KRWDZBQOSA-N (S)-amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-KRWDZBQOSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 230000008061 calcium-channel-blocking effect Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having 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 directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Definitions
- the present invention relates to a process for the preparation of [S( ⁇ )amlodipine-L(+)-hemi taratarte] from RS amlodipine base using L(+) tartaric acid in the presence of dimethyl sulfoxide.
- Amlodipine and its salts are long acting calcium channel blockers and are useful for the treatment of cardiovascular disorders. Racemic Amlodipine is currently being used as its besylate in the treatment of hypertension and angina. The preparation of racemic compound is described in European patent 0089167. Amlodipine is racemic compound and has chiral center at 4 position of the dihydropyridine ring.
- R(+) isomer is a potent inhibitor of smooth muscle cell migration (PCT/EP-94/02697).
- the S( ⁇ ) isomer is having calcium channel blocker activity while the R(+) isomers has little or no calcium channel blocking activity.
- the main object of the invention is to develop a technology for the preparation of S( ⁇ )amlodipine from racemic amlodipine using naturally occurring L-tataric acid.
- the invention provides a new and efficient process for the preparation of [S( ⁇ )amlodipine-L(+)hemi tartarte] in good yield with high enantiomeric purity by reacting RS amlodipine base with L(+) tartaric acid in an organic solvent at a temperature ranging from 20-35° C. for a period ranging from 16 to 24 hours, separating by filtration solid [R(+)amlodipine-L(+)-hemi taratarte], seeding the filtrate to obtain solid [S( ⁇ ) amlodipin-L(+)-hemi taratarte], filtering and recrystallising the solid, basifying to obtain S( ⁇ ) amlodipine.
- the organic solvent used for the reaction is dimethyl sulfoxide.
- the solvent used for crystallization is selected from the group consisting of methanol, ethanol and butanol.
- basification is done using metal hydroxides, carbonates or aq. Ammonia.
- the unique feature of the invention is preferential crystallization of enantiomer salt with respect to quantity of DMSO and time.
- the process of resolution of RS amlodipine using L(+) tartaric acid is shown in the scheme below:
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a process for the preparation of [S(−)amlodipine-L(+)-hemi taratarte] from RS amlodipine base using L(+) tartaric acid in the presence of dimethyl sulfoxide.
Description
- The present invention relates to a process for the preparation of [S(−)amlodipine-L(+)-hemi taratarte] from RS amlodipine base using L(+) tartaric acid in the presence of dimethyl sulfoxide.
- Amlodipine and its salts are long acting calcium channel blockers and are useful for the treatment of cardiovascular disorders. Racemic Amlodipine is currently being used as its besylate in the treatment of hypertension and angina. The preparation of racemic compound is described in European patent 0089167. Amlodipine is racemic compound and has chiral center at 4 position of the dihydropyridine ring.
- It has also been reported that the R(+) isomer is a potent inhibitor of smooth muscle cell migration (PCT/EP-94/02697). The S(−) isomer is having calcium channel blocker activity while the R(+) isomers has little or no calcium channel blocking activity.
- Prior art for the preparation of R and S enantiomers of amlodipine are a) resolution of amlodipine azide ester with optically active 2-methoxy-2-phenylethanol (J. Med. Chem., 29, 1696, 1986. J. E. Arrowsmith, S. F. Campbell, P. E. Cross, J. K. Stabs, R. A., Burges and EP Appl. 0331315A) or b) resolution of Amlodipine base with optically active camphanic acid [J. Med. Chem., 35, 3341, 1992, S. Goldman., J. Stoltefuss and L. Born) or c) resolution of RS.-amlodipine base to R(+) and S(−) isomer with L or D tartaric acid respectively in organic solvent DMSO {Peter L., Spargo U.S. Pat. No. 6,046,338; (2000), PCT 95/25722 (1995)] which indicate the use of both tartaric acids is essential.
- The main disadvantages of the prior art are:
- 1. The use of unnatural tartaric acid for the separation of S(−)amlodipine
- 2. The use of costlier camphanic acid or 2-methoxy-2-phenylethanol as a resolving agents.
- The main object of the invention is to develop a technology for the preparation of S(−)amlodipine from racemic amlodipine using naturally occurring L-tataric acid.
- Accordingly, the invention provides a new and efficient process for the preparation of [S(−)amlodipine-L(+)hemi tartarte] in good yield with high enantiomeric purity by reacting RS amlodipine base with L(+) tartaric acid in an organic solvent at a temperature ranging from 20-35° C. for a period ranging from 16 to 24 hours, separating by filtration solid [R(+)amlodipine-L(+)-hemi taratarte], seeding the filtrate to obtain solid [S(−) amlodipin-L(+)-hemi taratarte], filtering and recrystallising the solid, basifying to obtain S(−) amlodipine.
- In one embodiment of the present invention the organic solvent used for the reaction is dimethyl sulfoxide.
- In another embodiment of the present invention 0.5 mole of L(+) tartaric acid is used for the reaction.
- In another embodiment the solvent used for crystallization is selected from the group consisting of methanol, ethanol and butanol.
- In another embodiment of the invention basification is done using metal hydroxides, carbonates or aq. Ammonia.
- The unique feature of the invention is preferential crystallization of enantiomer salt with respect to quantity of DMSO and time. The process of resolution of RS amlodipine using L(+) tartaric acid is shown in the scheme below:
- The process of the present invention is described herein below with reference to examples which are illustrative only and should not be construed to limit the scope of the present invention in any manner.
- Amlodipine hemi L tartarate-mono-DMSO Solvate mp 160-162° C. [α] t=+24.32 (c=1, R(+) Amlodipine-hemi-L-tartarate mono DMSO Solvate and S(−) Amlodipine-hemi-L tartarate mono DMSO Solvate from (RS) Amlodipine.
- To a stirred solution of 10.50 gm (0.0256 mole), of RS Amlodipine in 30 ml of DMSO was added a solution of 1.93 (0.128) mole (0.5 equiv) of L(+) Tartaric acid in 30 ml DMSO. The solid starts separating from clear solution within 5-10 min. This was stirred for 3 hrs. and the solid was filtered off, washed with acetone and dried to give 6.66 gm, 46.15% R(+) MeOH). The filtrate was seeded with S(−)amlodipine hemi L(+) tartarate salt. and left overnight the solid was filtered off and washed with 10 ml acetone and dried to give 6.41 gm, 44.4% S(−) amlodipine-hemi L(+)-tartarate mono DMSO solvate.mp 169.5-171.5° C.=−14.1 (c=1, MeOH) 90% de by chiral HPLC. (J.Chrom., B 693, 367 (1997) J. Luksa, Dj. Josic, B. Podobinc, B. Furlan, M. Kremser]
- RS Amlodipine L(+)tartarate mono DMSO Solvate from RS Amlodipine
- The procedure as described in example 1 was repeated and the reaction was kept overnight. The solid filtered and dried to yeidl 14 gm, 97.9% RS Amlodipien L(+) tartarate mono DMSO solvate. Mp 148.5-151° C. (c=1 MeOH) 3.3% de by chiral HPLC.
- S(−)Amlodipine hemi L(+)tartarate monohydrate from S(−) Amlodipine-hemi-L-(+)tartarate monohydrate DMSO Solvate—Methanol as Solvent.
- 50 gms of S(−) Amlodipine-hemi-L(+)-tartarate mohohydrate DMSO solvate was dissolved in 250 ml refluxing methanol (30 min). The solution was kept overnight at room temperature (25-28° C.) with stirring. The solid was collected by filtration, washed with 100 ml methanol and dried at 50° C. in vacuo (2 hrs till constant wt.) to give 35 gm (80%). S(−)Amlodipine-hemi-L(+)-tartarate monohydrate. Mp 171-172° C.=114.1 (c=1, MeOH); 90% de chiral HPLC.
- S(−)Amlodipine hemi L(+)-tartarte mohohydrate from S(−) Amlodipine-hemi-L-(+)tartarate monohydrate DMSO Solvate—Ethanol as Solvent.
- The procedure was followed as mentioned in example 3 was using ethanol (150 ml) instead of methanol. The solid obtained was collected by filtration, washed with 50 ml cold ethanol and dried at 50° C. in vacuo (2 hrs till constant wt.) to give 30 gms (68%). S(−)Amlodipine hemi L(+)tartarate monohydrate mp 172.5-174° C.=17.44 (C=1, MeOH), 97% de chiral HPLC.
- S(−)Amlodipine from (S) (−)Amlodipine hemi L(+)tartarte mohonydrate.
- S(−)Amlodipine hemi L(+)tartarate mohohydrate (30 gms) was slurried in 60 ml CH 2Cl2 and 60 ml (6%) aqueous ammonia for 30 min. The organic solution was separated and washed with water. The organic extract was dried to give solid. The solid was filtered and dried at room temperature under vacuo to give 20 gms (82%) S(−)amlodipine mp 108-109° C. 30.55 (c=1, MeOH), 97.4% ee by chiral HPLC.
- S(−)Amlodipine from S(−)Amlodipine hemi L(+)tartarte mono DMSO Solvate
- S(−)Amlodipine hemi L(+)-tartarate mono DMSO solvate (30 gms) was slurried in 60 ml CH 2Cl2 and 60 ml (6%) aqueous ammonia for 30 min. The organic solution was separated and washed with water. The organic extract was dried over anhydrous sodium sulphate and concentrated. The residue was triturated with hexane to give solid 20.1 gms (92%) S(−)amlodipine. Mp107-107.5° C. 27.3 (c=1, MeOH), 90% ee by chiral HPLC.
Claims (6)
1. A process for the preparation of [S(−)amlodipine-L(+)-hemi tartarte which comprises reacting RS amlodipine base with L(+)tartaric acid in an organic solvent at a temperature ranging from 20-35° C. for the period ranging from 16 to 24 hours, separating the solid [R(=)amlodipin-L(+)-hemi tartarate] by filtration, seeding the filtrate to obtain solid [S(−)amlodipin-L(+)-hemi tartarate] by precipitation, filtering the solid and basifying to obtain [S(−)amlodipine-L(+)-hemi tartarte.
2. A process claimed in claim 1 wherein the solvent is DMSO
3. A process claimed in claim 1 wherein the solvent to amlodipine ratio is 5-6 ml/gm of amlodipine.
4. A process claimed in claim 1 wherein L-tartaric acid employed is about 0.5 mole per mole of amlodipine.
5. A process claimed in claim 1 wherein the solvate precipitated is S(−)smlodipine hemi L(+)-tartarate mono DMSO solvate.
6. A process claimed in claim 1 wherein a stirred solution of RS Amlodipine in DMSO was added to a solution of L(+)Tartaric acid in DMSO, the solid obtained separated by filtration, washed with acetone, dried to give R(+) MeOH), the filtrate seeded with S(−)amlodipine hemi L(+)tartarate salt, the solid so obtained filtered off and washed with acetone and dried to give S(−)amlodipine-hemi L(+)-tartarate mono DMSO solvate.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/098,502 US20030176706A1 (en) | 2002-03-18 | 2002-03-18 | Process for the preparation of [S(-) amlodipine - L (+)- hemitartarate] |
| US10/937,564 US7148358B2 (en) | 2002-03-18 | 2004-09-10 | Process for the preparation of S(−) amlodipine-L(+)-hemi taratarte |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/098,502 US20030176706A1 (en) | 2002-03-18 | 2002-03-18 | Process for the preparation of [S(-) amlodipine - L (+)- hemitartarate] |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/937,564 Continuation US7148358B2 (en) | 2002-03-18 | 2004-09-10 | Process for the preparation of S(−) amlodipine-L(+)-hemi taratarte |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20030176706A1 true US20030176706A1 (en) | 2003-09-18 |
Family
ID=28039376
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/098,502 Abandoned US20030176706A1 (en) | 2002-03-18 | 2002-03-18 | Process for the preparation of [S(-) amlodipine - L (+)- hemitartarate] |
| US10/937,564 Expired - Fee Related US7148358B2 (en) | 2002-03-18 | 2004-09-10 | Process for the preparation of S(−) amlodipine-L(+)-hemi taratarte |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/937,564 Expired - Fee Related US7148358B2 (en) | 2002-03-18 | 2004-09-10 | Process for the preparation of S(−) amlodipine-L(+)-hemi taratarte |
Country Status (1)
| Country | Link |
|---|---|
| US (2) | US20030176706A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004024689A1 (en) * | 2002-09-11 | 2004-03-25 | Hanlim Pharmaceutical Co., Ltd. | Processes for the preparation of s-(-)-amlodipine |
| WO2008026838A1 (en) * | 2006-08-30 | 2008-03-06 | Chemtech Research Incorporation | Method for preparing an optically active amlodipine |
| HRP20040520B1 (en) * | 2004-06-08 | 2008-06-30 | Belupo - Lijekovi I Kozmetika D.D. | Resolution (r,s)-2-(2-aminoethoxymethyl)-3-ethoxycarbonyl-4-(2-chlorphenyl)-5-methoxycarbonyl-6-methyl-1,4- dihydropiridine lipase catalysed |
| EP1975167A1 (en) * | 2007-03-30 | 2008-10-01 | Esteve Quimica, S.A. | Acetone solvate of phthaloyl amlodipine |
| US20080249314A1 (en) * | 2004-12-02 | 2008-10-09 | Sk Chemicals Co., Ltd. | Optical Resolution Method of Amlodipine |
| US20080262239A1 (en) * | 2004-10-20 | 2008-10-23 | Emcure Pharmaceuticals Limited | Process for Producing Enantiomer of Amlodipine in High Optical Purity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5750707A (en) * | 1994-03-24 | 1998-05-12 | Pfizer Inc. | Separation of the enantiomers of amlodipine via their diastereomeric tartrates |
| US6057344A (en) * | 1991-11-26 | 2000-05-02 | Sepracor, Inc. | Methods for treating hypertension, and angina using optically pure (-) amlodipine |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20040062575A (en) * | 2001-10-24 | 2004-07-07 | 세프라코 아이엔시. | Method of resolving amlodipine racemate |
-
2002
- 2002-03-18 US US10/098,502 patent/US20030176706A1/en not_active Abandoned
-
2004
- 2004-09-10 US US10/937,564 patent/US7148358B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6057344A (en) * | 1991-11-26 | 2000-05-02 | Sepracor, Inc. | Methods for treating hypertension, and angina using optically pure (-) amlodipine |
| US5750707A (en) * | 1994-03-24 | 1998-05-12 | Pfizer Inc. | Separation of the enantiomers of amlodipine via their diastereomeric tartrates |
| US6046338A (en) * | 1994-03-24 | 2000-04-04 | Pfizer Inc. | Separation of the enantiomers of amlodipine via their diastereomeric tartrates |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060014961A1 (en) * | 2002-09-11 | 2006-01-19 | Hanlim Pharmaceutical Co., Ltd. | Processes for the preparation of s-(-)-amlodipine |
| US7202365B2 (en) | 2002-09-11 | 2007-04-10 | Hamlim Pharmaceutical Co., Ltd. | Processes for the preparation of S-(-)-amlodipine |
| US20070155969A1 (en) * | 2002-09-11 | 2007-07-05 | Hanlim Pharmaceutical Co., Ltd. | Processes for the preparation of s-(-)-amlodipine |
| WO2004024689A1 (en) * | 2002-09-11 | 2004-03-25 | Hanlim Pharmaceutical Co., Ltd. | Processes for the preparation of s-(-)-amlodipine |
| US7482464B2 (en) * | 2002-09-11 | 2009-01-27 | Hanlim Pharmaceutical Co., Ltd. | Processes for the preparation of S-(-)-amlodipine |
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| US20110021783A1 (en) * | 2004-10-20 | 2011-01-27 | Emcure Pharmaceuticals Limited | Process for producing enantiomer of amlodipine in high optical purity |
| US20080262239A1 (en) * | 2004-10-20 | 2008-10-23 | Emcure Pharmaceuticals Limited | Process for Producing Enantiomer of Amlodipine in High Optical Purity |
| US7858801B2 (en) | 2004-10-20 | 2010-12-28 | Emcure Pharmaceuticals Limited | Process for producing enantiomer of amlodipine in high optical purity |
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| KR101088488B1 (en) | 2006-08-30 | 2011-11-30 | 주식회사 씨트리 | Method for preparing an optically active amlodipine |
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| Publication number | Publication date |
|---|---|
| US7148358B2 (en) | 2006-12-12 |
| US20050176781A1 (en) | 2005-08-11 |
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