CN109206361A - 用于托法替尼制备的有用中间体手性3-氨基哌啶的改进制备方法 - Google Patents
用于托法替尼制备的有用中间体手性3-氨基哌啶的改进制备方法 Download PDFInfo
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- CN109206361A CN109206361A CN201810568925.4A CN201810568925A CN109206361A CN 109206361 A CN109206361 A CN 109206361A CN 201810568925 A CN201810568925 A CN 201810568925A CN 109206361 A CN109206361 A CN 109206361A
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
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- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
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Classifications
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- 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
- C07D211/36—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 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
- C07D211/56—Nitrogen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2291—Olefins
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/822—Rhodium
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17178755.9 | 2017-06-29 | ||
| EP17178755.9A EP3421455B1 (en) | 2017-06-29 | 2017-06-29 | Improved process for the preparation of chiral 3-amino-piperidins, useful intermediates for the preparation of tofacitinib |
Publications (1)
| Publication Number | Publication Date |
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| CN109206361A true CN109206361A (zh) | 2019-01-15 |
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| CN201810568925.4A Pending CN109206361A (zh) | 2017-06-29 | 2018-06-05 | 用于托法替尼制备的有用中间体手性3-氨基哌啶的改进制备方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20190002407A1 (enExample) |
| EP (1) | EP3421455B1 (enExample) |
| JP (1) | JP6917949B2 (enExample) |
| CN (1) | CN109206361A (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109761884A (zh) * | 2019-01-30 | 2019-05-17 | 湖北扬信医药科技有限公司 | 一种手性胺b的制备方法及其应用 |
| CN113125587A (zh) * | 2019-12-30 | 2021-07-16 | 成都百裕制药股份有限公司 | 一种托法替尼中间体及其对映异构体的检测方法 |
| CN113614069A (zh) * | 2019-04-05 | 2021-11-05 | 柳韩洋行 | 用于制备(3r,4r)-1-苄基-n,4-二甲基哌啶-3-胺或其盐的方法以及使用其制备托法替尼的方法 |
| CN113899831A (zh) * | 2021-10-11 | 2022-01-07 | 湖北科益药业股份有限公司 | 一种枸橼酸托法替布起始物料的液相色谱检测方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1984877A (zh) * | 2004-07-08 | 2007-06-20 | 默克公司 | 四取代的烯酰胺的形成及其立体选择性还原 |
| CN101233138A (zh) * | 2005-07-29 | 2008-07-30 | 辉瑞产品公司 | 吡咯并[2，3-d]嘧啶衍生物、其中间体和合成方法 |
| JP2015507023A (ja) * | 2012-02-21 | 2015-03-05 | セルジーン コーポレイション | アミノスルホン化合物の調製のための不斉合成方法 |
| CN105189521A (zh) * | 2013-02-12 | 2015-12-23 | 拜耳医药股份公司 | 结合至血小板特异性糖蛋白IIb/IIIa的金属螯合化合物 |
| CN105431414A (zh) * | 2013-07-08 | 2016-03-23 | 先正达参股股份有限公司 | 用作杀线虫剂的4元环甲酰胺 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6258979B1 (en) * | 1999-11-22 | 2001-07-10 | Henri Kagan | Chiral ferrocene phosphines active in asymmetric catalysis |
| EP1572649A2 (en) * | 2002-11-21 | 2005-09-14 | Pfizer Products Inc. | 3-amino-piperidine derivatives and processes for their preparation |
| CL2008000017A1 (es) * | 2007-01-04 | 2008-08-01 | Prosidion Ltd | Compuestos derivados de heterociclos de nitrogeno y oxigeno, agonistas de gpcr; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de la obesidad, diabetes, sindrome metabolico, hiperlipidemia, toleranci |
| AR070176A1 (es) * | 2008-01-17 | 2010-03-17 | Novartis Ag | Procesos de sintesis de inhibidores de nep, compuestos intermediarios y uso de los mismos en la sintesis |
| CN102459270B (zh) * | 2009-04-20 | 2015-04-29 | 奥斯拜客斯制药有限公司 | Janus激酶3的哌啶抑制剂 |
| ES2608780T3 (es) * | 2010-08-23 | 2017-04-17 | Novartis Ag | Nuevo proceso para la preparación de intermediarios útiles para la elaboración de inhibidores de NEP |
| AU2012284127A1 (en) * | 2011-07-18 | 2013-05-02 | Adolor Corporation | Processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto |
| WO2014195978A2 (en) | 2013-06-05 | 2014-12-11 | Msn Laboratories Limited | PROCESS FOR THE PREPARATION OF (3R,4R)-4-METHYL-3-(METHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL-AMINO)-ß-OXO-1-PIPERIDINEPROPANENITRILE AND ITS SALTS |
| TW201617321A (zh) * | 2014-09-18 | 2016-05-16 | 第一三共股份有限公司 | 光學活性吉草酸衍生物之製法 |
| EP3078665A1 (en) * | 2015-04-10 | 2016-10-12 | OLON S.p.A. | Efficient method for the preparation of tofacitinib citrate |
-
2017
- 2017-06-29 EP EP17178755.9A patent/EP3421455B1/en active Active
-
2018
- 2018-06-05 CN CN201810568925.4A patent/CN109206361A/zh active Pending
- 2018-06-25 JP JP2018119595A patent/JP6917949B2/ja active Active
- 2018-06-25 US US16/017,390 patent/US20190002407A1/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1984877A (zh) * | 2004-07-08 | 2007-06-20 | 默克公司 | 四取代的烯酰胺的形成及其立体选择性还原 |
| CN101233138A (zh) * | 2005-07-29 | 2008-07-30 | 辉瑞产品公司 | 吡咯并[2，3-d]嘧啶衍生物、其中间体和合成方法 |
| JP2015507023A (ja) * | 2012-02-21 | 2015-03-05 | セルジーン コーポレイション | アミノスルホン化合物の調製のための不斉合成方法 |
| CN105189521A (zh) * | 2013-02-12 | 2015-12-23 | 拜耳医药股份公司 | 结合至血小板特异性糖蛋白IIb/IIIa的金属螯合化合物 |
| CN105431414A (zh) * | 2013-07-08 | 2016-03-23 | 先正达参股股份有限公司 | 用作杀线虫剂的4元环甲酰胺 |
Non-Patent Citations (4)
| Title |
|---|
| DAVID H. BROWN RIPIN ET AL.: "Development of a Scaleable Route for the Production of cis-N-Benzyl-3-methylamino-4-methylpiperidine", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
| WEILING CAI ET AL.: "Investigation of Practical Routes for the Kilogram-Scale Production of cis-3-Methylamino-4-methylpiperidines", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
| X. ERIC HU ET AL.: "Synthesis of trans-(3S)-Amino-(4R)-alkyl and -(4S)-Aryl-piperidines via Ring-Closing Metathesis Reaction", 《ORGANIC LETTERS》 * |
| YOGESH S. PATIL ET AL.: "An Improved and Efficient Process for the Preparation of Tofacitinib Citrate", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109761884A (zh) * | 2019-01-30 | 2019-05-17 | 湖北扬信医药科技有限公司 | 一种手性胺b的制备方法及其应用 |
| CN113614069A (zh) * | 2019-04-05 | 2021-11-05 | 柳韩洋行 | 用于制备(3r,4r)-1-苄基-n,4-二甲基哌啶-3-胺或其盐的方法以及使用其制备托法替尼的方法 |
| CN113614069B (zh) * | 2019-04-05 | 2024-05-28 | 柳韩洋行 | 用于制备(3r,4r)-1-苄基-n,4-二甲基哌啶-3-胺或其盐的方法以及使用其制备托法替尼的方法 |
| CN113125587A (zh) * | 2019-12-30 | 2021-07-16 | 成都百裕制药股份有限公司 | 一种托法替尼中间体及其对映异构体的检测方法 |
| CN113899831A (zh) * | 2021-10-11 | 2022-01-07 | 湖北科益药业股份有限公司 | 一种枸橼酸托法替布起始物料的液相色谱检测方法 |
| CN113899831B (zh) * | 2021-10-11 | 2023-08-15 | 湖北科益药业股份有限公司 | 一种枸橼酸托法替布起始物料的液相色谱检测方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3421455A1 (en) | 2019-01-02 |
| US20190002407A1 (en) | 2019-01-03 |
| EP3421455B1 (en) | 2019-03-27 |
| JP2019023181A (ja) | 2019-02-14 |
| JP6917949B2 (ja) | 2021-08-11 |
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