AU765194B2 - Processes and intermediates for preparing 2-substituted piperidine stereoisomers - Google Patents
Processes and intermediates for preparing 2-substituted piperidine stereoisomers Download PDFInfo
- Publication number
- AU765194B2 AU765194B2 AU75950/98A AU7595098A AU765194B2 AU 765194 B2 AU765194 B2 AU 765194B2 AU 75950/98 A AU75950/98 A AU 75950/98A AU 7595098 A AU7595098 A AU 7595098A AU 765194 B2 AU765194 B2 AU 765194B2
- Authority
- AU
- Australia
- Prior art keywords
- erythro
- threo
- stereoisomers
- piperidine
- reacting
- 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
Links
- -1 2-substituted piperidine Chemical class 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims description 38
- 239000000543 intermediate Substances 0.000 title description 4
- 239000002253 acid Substances 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 26
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims abstract description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims abstract description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002585 base Substances 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 150000003053 piperidines Chemical class 0.000 claims abstract description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 230000001376 precipitating effect Effects 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 28
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 13
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 13
- 235000019439 ethyl acetate Nutrition 0.000 claims description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
- 229960001270 d- tartaric acid Drugs 0.000 claims 2
- 229940093499 ethyl acetate Drugs 0.000 claims 2
- 101150015280 Cel gene Proteins 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 10
- 239000003795 chemical substances by application Substances 0.000 abstract description 6
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 125000005233 alkylalcohol group Chemical group 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 6
- 229960001344 methylphenidate Drugs 0.000 description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 206010001513 AIDS related complex Diseases 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000006345 epimerization reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- LJLMNWPXAYKPGV-UHFFFAOYSA-N 2-phenylpiperidine-2-acetamide Chemical compound C=1C=CC=CC=1C(C(=O)N)C1CCCCN1 LJLMNWPXAYKPGV-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 239000001358 L(+)-tartaric acid Substances 0.000 description 1
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002743 euphoric effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/792,661 US5965734A (en) | 1997-01-31 | 1997-01-31 | Processes and intermediates for preparing 2-substituted piperidine stereoisomers |
| PCT/US1998/010599 WO1999061425A1 (en) | 1997-01-31 | 1998-05-26 | Processes and intermediates for preparing 2-substituted piperidine stereoisomers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7595098A AU7595098A (en) | 1999-12-13 |
| AU765194B2 true AU765194B2 (en) | 2003-09-11 |
Family
ID=26794135
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU75950/98A Expired AU765194B2 (en) | 1997-01-31 | 1998-05-26 | Processes and intermediates for preparing 2-substituted piperidine stereoisomers |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US5965734A (enExample) |
| EP (2) | EP1082307B1 (enExample) |
| JP (1) | JP4491135B2 (enExample) |
| AT (2) | ATE304531T1 (enExample) |
| AU (1) | AU765194B2 (enExample) |
| CA (1) | CA2333089C (enExample) |
| CY (1) | CY1108818T1 (enExample) |
| DE (2) | DE69831611T2 (enExample) |
| DK (2) | DK1082307T3 (enExample) |
| ES (2) | ES2320012T3 (enExample) |
| PT (1) | PT1612207E (enExample) |
| WO (1) | WO1999061425A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6486177B2 (en) * | 1995-12-04 | 2002-11-26 | Celgene Corporation | Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate |
| US5922736A (en) * | 1995-12-04 | 1999-07-13 | Celegene Corporation | Chronic, bolus administration of D-threo methylphenidate |
| US5837284A (en) * | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US6962997B1 (en) * | 1997-05-22 | 2005-11-08 | Celgene Corporation | Process and intermediates for resolving piperidyl acetamide steroisomers |
| US6359139B1 (en) * | 2000-11-07 | 2002-03-19 | Celgene Corporation | Methods for production of piperidyl acetamide stereoisomers |
| US20020187192A1 (en) * | 2001-04-30 | 2002-12-12 | Yatindra Joshi | Pharmaceutical composition which reduces or eliminates drug abuse potential |
| US20030073681A1 (en) * | 2001-08-21 | 2003-04-17 | Hauske James R. | 2-substituted piperidines that are ligands for monoamine receptors and transporters |
| US6638533B2 (en) | 2002-01-03 | 2003-10-28 | George Krsek | Pulse dosage formulations of methylphenidate and method to prepare same |
| US20050239830A1 (en) * | 2004-04-26 | 2005-10-27 | Vikram Khetani | Methods of diminishing co-abuse potential |
| CA2591247A1 (en) * | 2004-12-09 | 2006-06-15 | Celgene Corporation | Treatment of patients suffering from a disease having a family history or diagnosis of tics or tourette's syndrome with d-threo methylphenidate |
| ITMI20042415A1 (it) * | 2004-12-17 | 2005-03-17 | Clariant Lsm Italia Spa | Sintesi di alfa-aril-alfa-piperid-2-il-acetammidi e loro idrolisi acida |
| US9233924B2 (en) | 2014-03-11 | 2016-01-12 | Ampac Fine Chemicals Llc | Methods for preparing D-threo methylphenidate using diazomethane, and compositions thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2507631A (en) * | 1944-01-19 | 1950-05-16 | Ciba Pharm Prod Inc | Pyridine and piperidine compounds and process of making same |
| US2957880A (en) * | 1953-12-23 | 1960-10-25 | Ciba Pharm Prod Inc | Process for the conversion of stereoisomers |
| JPS5630978A (en) * | 1979-08-24 | 1981-03-28 | Kyowa Hakko Kogyo Co Ltd | Novel mitomycin and its preparation |
| US4978744A (en) * | 1989-01-27 | 1990-12-18 | Arizona Board Of Regents | Synthesis of dolastatin 10 |
| US5075315A (en) * | 1990-05-17 | 1991-12-24 | Mcneilab, Inc. | Antipsychotic hexahydro-2H-indeno[1,2-c]pyridine derivatives |
| WO1993019063A1 (en) * | 1992-03-16 | 1993-09-30 | Merck Sharp & Dohme Limited | Benzodiazepine derivatives, compositions containing them and their use in therapy |
| US5696111A (en) * | 1993-11-22 | 1997-12-09 | Merck & Co., Inc. | 3-acylaminobenzazepines |
| EP0771789B1 (en) * | 1995-10-30 | 2000-02-16 | F. Hoffmann-La Roche Ag | 1 alpha, 26-dihydroxy-D-homo-vitamin D3 |
| DE19615119A1 (de) * | 1996-04-17 | 1997-10-23 | Bayer Ag | Neue Arylessigsäureamide |
-
1997
- 1997-01-31 US US08/792,661 patent/US5965734A/en not_active Expired - Lifetime
-
1998
- 1998-05-26 DK DK98923727T patent/DK1082307T3/da active
- 1998-05-26 ES ES05077084T patent/ES2320012T3/es not_active Expired - Lifetime
- 1998-05-26 DE DE69831611T patent/DE69831611T2/de not_active Expired - Lifetime
- 1998-05-26 DK DK05077084T patent/DK1612207T3/da active
- 1998-05-26 CA CA002333089A patent/CA2333089C/en not_active Expired - Lifetime
- 1998-05-26 PT PT05077084T patent/PT1612207E/pt unknown
- 1998-05-26 AT AT98923727T patent/ATE304531T1/de active
- 1998-05-26 WO PCT/US1998/010599 patent/WO1999061425A1/en not_active Ceased
- 1998-05-26 DE DE69840457T patent/DE69840457D1/de not_active Expired - Lifetime
- 1998-05-26 EP EP98923727A patent/EP1082307B1/en not_active Expired - Lifetime
- 1998-05-26 JP JP2000550831A patent/JP4491135B2/ja not_active Expired - Fee Related
- 1998-05-26 AU AU75950/98A patent/AU765194B2/en not_active Expired
- 1998-05-26 AT AT05077084T patent/ATE420073T1/de active
- 1998-05-26 EP EP05077084A patent/EP1612207B1/en not_active Expired - Lifetime
- 1998-05-26 ES ES98923727T patent/ES2249830T3/es not_active Expired - Lifetime
-
2009
- 2009-02-26 CY CY20091100223T patent/CY1108818T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1082307A4 (en) | 2004-04-14 |
| ATE304531T1 (de) | 2005-09-15 |
| PT1612207E (pt) | 2009-02-04 |
| EP1612207B1 (en) | 2009-01-07 |
| WO1999061425A1 (en) | 1999-12-02 |
| ES2320012T3 (es) | 2009-05-18 |
| HK1090915A1 (en) | 2007-01-05 |
| EP1082307B1 (en) | 2005-09-14 |
| JP2002516313A (ja) | 2002-06-04 |
| AU7595098A (en) | 1999-12-13 |
| DE69831611T2 (de) | 2006-06-14 |
| EP1082307A1 (en) | 2001-03-14 |
| JP4491135B2 (ja) | 2010-06-30 |
| CA2333089C (en) | 2008-10-14 |
| DE69831611D1 (de) | 2005-10-20 |
| CA2333089A1 (en) | 1999-12-02 |
| US5965734A (en) | 1999-10-12 |
| EP1612207A1 (en) | 2006-01-04 |
| DK1612207T3 (da) | 2009-05-04 |
| ES2249830T3 (es) | 2006-04-01 |
| ATE420073T1 (de) | 2009-01-15 |
| DE69840457D1 (de) | 2009-02-26 |
| CY1108818T1 (el) | 2014-04-09 |
| DK1082307T3 (da) | 2005-12-19 |
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