JP2019023181A5 - - Google Patents
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- JP2019023181A5 JP2019023181A5 JP2018119595A JP2018119595A JP2019023181A5 JP 2019023181 A5 JP2019023181 A5 JP 2019023181A5 JP 2018119595 A JP2018119595 A JP 2018119595A JP 2018119595 A JP2018119595 A JP 2018119595A JP 2019023181 A5 JP2019023181 A5 JP 2019023181A5
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- Prior art keywords
- formula
- compound
- enantiomeric excess
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- 238000000034 method Methods 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- -1 tetrafluoroborate Chemical compound 0.000 claims description 11
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- OXTKXGVJXOBALA-UHFFFAOYSA-N ethyl-bis(2-methylphenyl)phosphane Chemical compound C=1C=CC=C(C)C=1P(CC)C1=CC=CC=C1C OXTKXGVJXOBALA-UHFFFAOYSA-N 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims 13
- 230000003287 optical effect Effects 0.000 claims 10
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 6
- 239000002904 solvent Substances 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 239000004012 Tofacitinib Substances 0.000 claims 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 claims 2
- 229960001350 tofacitinib Drugs 0.000 claims 2
- NVKDDQBZODSEIN-OCCSQVGLSA-N (3r,4r)-1-benzyl-n,4-dimethylpiperidin-3-amine Chemical compound C1C[C@@H](C)[C@@H](NC)CN1CC1=CC=CC=C1 NVKDDQBZODSEIN-OCCSQVGLSA-N 0.000 claims 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims 1
- NVKDDQBZODSEIN-UHFFFAOYSA-N 1-benzyl-n,4-dimethylpiperidin-3-amine Chemical compound C1CC(C)C(NC)CN1CC1=CC=CC=C1 NVKDDQBZODSEIN-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 150000001993 dienes Chemical class 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- GOPBTCMAUMSOBX-UHFFFAOYSA-M [Rh+].C1CC=CCCC=C1.C1CC=CCCC=C1.[O-]S(=O)(=O)C(F)(F)F Chemical compound [Rh+].C1CC=CCCC=C1.C1CC=CCCC=C1.[O-]S(=O)(=O)C(F)(F)F GOPBTCMAUMSOBX-UHFFFAOYSA-M 0.000 description 4
- 208000012839 conversion disease Diseases 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- JFUNGPLAZARVCR-UHFFFAOYSA-N (1-benzyl-4-methyl-3,6-dihydro-2H-pyridin-5-yl)carbamic acid Chemical compound CC1=C(CN(CC1)CC2=CC=CC=C2)NC(=O)O JFUNGPLAZARVCR-UHFFFAOYSA-N 0.000 description 3
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 0 C[C@](C(CC(C[Fe]*1=*CCCC1)C1)C1P(c(cc1C)cc(C)c1OC)c(cc1C)cc(C)c1OC)P(*)C(C)(C)C Chemical compound C[C@](C(CC(C[Fe]*1=*CCCC1)C1)C1P(c(cc1C)cc(C)c1OC)c(cc1C)cc(C)c1OC)P(*)C(C)(C)C 0.000 description 2
- ZYPSDHCBNMCWCZ-JQDLGSOUSA-N [(1r)-1-[2-bis[4-(trifluoromethyl)phenyl]phosphanylcyclopentyl]ethyl]-ditert-butylphosphane;cyclopentane;iron Chemical compound [Fe].[CH]1[CH][CH][CH][CH]1.CC(C)(C)P(C(C)(C)C)[C@H](C)[C]1[CH][CH][CH][C]1P(C=1C=CC(=CC=1)C(F)(F)F)C1=CC=C(C(F)(F)F)C=C1 ZYPSDHCBNMCWCZ-JQDLGSOUSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- WHOBZBLBTZHMGY-UHFFFAOYSA-N ditert-butyl(ethyl)phosphane Chemical compound CCP(C(C)(C)C)C(C)(C)C WHOBZBLBTZHMGY-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 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
- CMMMHFCMUONCEF-UHFFFAOYSA-N CC(CCN(CC1=CC=CC=C1)C1)=C1OC(N)=O Chemical compound CC(CCN(CC1=CC=CC=C1)C1)=C1OC(N)=O CMMMHFCMUONCEF-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- DPOGTJDEMBEUSH-UHFFFAOYSA-N dicyclohexyl(ethyl)phosphane Chemical compound C1CCCCC1P(CC)C1CCCCC1 DPOGTJDEMBEUSH-UHFFFAOYSA-N 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WUOIAOOSKMHJOV-UHFFFAOYSA-N ethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CC)C1=CC=CC=C1 WUOIAOOSKMHJOV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2019023181A JP2019023181A (ja) | 2019-02-14 |
| JP2019023181A5 true JP2019023181A5 (OSRAM) | 2021-05-20 |
| JP6917949B2 JP6917949B2 (ja) | 2021-08-11 |
Family
ID=59258098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018119595A Active JP6917949B2 (ja) | 2017-06-29 | 2018-06-25 | トファシチニブの調製のための有用な中間体であるキラル３−アミノ−ピペリジンの調製のための改良された方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20190002407A1 (OSRAM) |
| EP (1) | EP3421455B1 (OSRAM) |
| JP (1) | JP6917949B2 (OSRAM) |
| CN (1) | CN109206361A (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109761884B (zh) * | 2019-01-30 | 2020-03-31 | 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 |
| JP7515510B2 (ja) * | 2019-04-05 | 2024-07-12 | ユーハン・コーポレイション | （３ｒ，４ｒ）－１－ベンジル－ｎ，４－ジメチルピペリジン－３－アミンまたはその塩の製造方法、およびそれを使用したトファシチニブの製造方法 |
| CN113125587B (zh) * | 2019-12-30 | 2022-05-24 | 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 |
| 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 |
Family Cites Families (15)
| 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 |
| AU2003278529A1 (en) * | 2002-11-21 | 2004-06-15 | Pfizer Products Inc. | 3-amino-piperidine derivatives and processes for their preparation |
| CA2672687A1 (en) * | 2004-07-08 | 2006-02-16 | Merck & Co., Inc. | Formation of tetra-substituted enamides and stereoselective reduction thereof |
| 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 |
| AR064736A1 (es) * | 2007-01-04 | 2009-04-22 | Prosidion Ltd | Agonistas de gpcr |
| 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 |
| ES2552805T3 (es) * | 2009-04-20 | 2015-12-02 | Auspex Pharmaceuticals, Llc | Inhibidores piperidínicos de la cinasa Janus 3 |
| CA2806501A1 (en) * | 2010-08-23 | 2012-03-01 | Novartis Ag | New process for the preparation of intermediates useful for the manufacture nep inhibitors |
| CA2842183A1 (en) * | 2011-07-18 | 2013-01-24 | Adolor Corporation | Processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto |
| US9126906B2 (en) * | 2012-02-21 | 2015-09-08 | Celgene Corporation | Asymmetric synthetic processes for the preparation of aminosulfone compounds |
| US20160008490A1 (en) * | 2013-02-12 | 2016-01-14 | Bayer Pharma Aktiengesellschaft | Metal chelate compounds for binding to the platelet specific glycoprotein iib/iiia |
| 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 |
| UA117251C2 (uk) * | 2013-07-08 | 2018-07-10 | Сінгента Партісіпейшнс Аг | 4-членні кільцеві карбоксамідні сполуки, що застосовуються як нематоциди |
| EP3196193B1 (en) * | 2014-09-18 | 2018-12-19 | Daiichi Sankyo Company, Limited | Method for producing optically active valeric acid derivative |
| 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
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