NO330013B1 - Fremgangsmater for fremstillingen av 4-[[4-[[4-(2-cyanoetenyl)-2,6-dimetylfenyl]amino]-2-pyrimidinyl]amino]benzonitril - Google Patents
Fremgangsmater for fremstillingen av 4-[[4-[[4-(2-cyanoetenyl)-2,6-dimetylfenyl]amino]-2-pyrimidinyl]amino]benzonitril Download PDFInfo
- Publication number
- NO330013B1 NO330013B1 NO20050524A NO20050524A NO330013B1 NO 330013 B1 NO330013 B1 NO 330013B1 NO 20050524 A NO20050524 A NO 20050524A NO 20050524 A NO20050524 A NO 20050524A NO 330013 B1 NO330013 B1 NO 330013B1
- Authority
- NO
- Norway
- Prior art keywords
- addition salt
- acid addition
- formula
- amino
- stereochemically isomeric
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- YIBOMRUWOWDFLG-UHFFFAOYSA-N 4-[[4-[4-(2-cyanoethenyl)-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C=CC#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-UHFFFAOYSA-N 0.000 title claims description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 135
- 150000003839 salts Chemical class 0.000 claims abstract description 93
- 239000002253 acid Substances 0.000 claims abstract description 91
- 150000001412 amines Chemical group 0.000 claims abstract description 49
- 239000003054 catalyst Substances 0.000 claims abstract description 36
- 239000002904 solvent Substances 0.000 claims abstract description 36
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 32
- 230000008569 process Effects 0.000 claims abstract description 15
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 56
- 238000011282 treatment Methods 0.000 claims description 29
- 239000012458 free base Substances 0.000 claims description 21
- 239000002585 base Substances 0.000 claims description 16
- 125000001475 halogen functional group Chemical group 0.000 claims description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 14
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- 239000003513 alkali Substances 0.000 claims description 11
- 230000018044 dehydration Effects 0.000 claims description 9
- 238000006297 dehydration reaction Methods 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000005605 benzo group Chemical group 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 47
- -1 2-cyanoethenyl Chemical group 0.000 abstract description 17
- 150000001408 amides Chemical class 0.000 abstract description 3
- JNRBSZUSHVFWIK-UHFFFAOYSA-N 3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile Chemical compound CC1=CC(C=CC#N)=CC(C)=C1N JNRBSZUSHVFWIK-UHFFFAOYSA-N 0.000 abstract description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 abstract 3
- 239000000543 intermediate Substances 0.000 description 85
- 239000000203 mixture Substances 0.000 description 45
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- 239000000047 product Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
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- 239000003446 ligand Substances 0.000 description 8
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
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- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 description 4
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
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- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/20—Preparation of carboxylic acid nitriles by dehydration of carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02078306 | 2002-08-09 | ||
| PCT/EP2003/050366 WO2004016581A1 (en) | 2002-08-09 | 2003-08-07 | Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20050524L NO20050524L (no) | 2005-02-01 |
| NO330013B1 true NO330013B1 (no) | 2011-02-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20050524A NO330013B1 (no) | 2002-08-09 | 2005-02-01 | Fremgangsmater for fremstillingen av 4-[[4-[[4-(2-cyanoetenyl)-2,6-dimetylfenyl]amino]-2-pyrimidinyl]amino]benzonitril |
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| CN (4) | CN101481356B (da) |
| AR (1) | AR040964A1 (da) |
| AU (1) | AU2003266413B2 (da) |
| BR (1) | BR0313545B1 (da) |
| CA (2) | CA2686429C (da) |
| CL (1) | CL2010000284A1 (da) |
| CY (1) | CY1114428T1 (da) |
| DK (1) | DK1529032T3 (da) |
| EA (1) | EA007953B1 (da) |
| ES (1) | ES2422196T3 (da) |
| HK (4) | HK1129671A1 (da) |
| HR (1) | HRP20050104B1 (da) |
| IL (1) | IL166710A (da) |
| IS (1) | IS2980B (da) |
| MX (1) | MXPA05001541A (da) |
| MY (1) | MY144894A (da) |
| NO (1) | NO330013B1 (da) |
| NZ (1) | NZ538611A (da) |
| PL (1) | PL208533B1 (da) |
| PT (1) | PT1529032E (da) |
| SI (1) | SI1529032T1 (da) |
| TW (1) | TWI314146B (da) |
| WO (1) | WO2004016581A1 (da) |
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| US7638522B2 (en) * | 2001-08-13 | 2009-12-29 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile |
| JO3429B1 (ar) | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
| MY169670A (en) | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| US8101629B2 (en) | 2001-08-13 | 2012-01-24 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
| JP4822707B2 (ja) * | 2002-08-09 | 2011-11-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ４−［［４−［［４−（２−シアノエテニル）−２，６−ジメチルフェニル］アミノ］−２−ピリミジニル］アミノ］ベンゾニトリルの製造方法 |
| EA200500721A1 (ru) * | 2002-11-28 | 2005-12-29 | Шеринг Акциенгезельшафт | Пиримидины, ингибирующие chk, pdk и акт, их получение и применение в качестве лекарственных средств |
| WO2005123662A1 (en) * | 2004-06-18 | 2005-12-29 | Janssen Pharmaceutica N.V. | Modified heck reaction |
| PL1632232T6 (pl) * | 2004-09-02 | 2022-06-27 | Janssen Pharmaceutica Nv | Sól 4-[[4-[[4-(2-cyjanoetenylo)-2,6-dimetylofenylo]amino]-2-pirymidynylo]amino]benzonitrylu |
| EP1632232B3 (en) * | 2004-09-02 | 2022-03-30 | Janssen Pharmaceutica NV | Salt of 4[[4-[[4-(2-Cyanoethenyl)-2,6-dimethylphenyl]amino]-2-Pyrimidinyl]amino]benzonitrile |
| EP1789139B1 (en) * | 2004-09-02 | 2012-03-21 | Janssen Pharmaceutica NV | Fumarate of 4-((4-((4-(2-cyanoethenyl)-2,6-dimethylphenyl amino -2-pyrimidinyl amino benzonitrile |
| EA011036B1 (ru) * | 2004-09-02 | 2008-12-30 | Янссен Фармацевтика Н.В. | Фумарат 4-[[4-[[4-(2-цианоэтенил)-2,6-диметилфенил]амино]-2-пиримидинил]амино]бензонитрила |
| CN101068597B (zh) * | 2004-09-02 | 2012-04-18 | 詹森药业有限公司 | 4-((4-((4-(2-氰基乙烯基)-2,6-二甲基苯基)氨基)-2-嘧啶基)氨基)苄腈的富马酸盐 |
| US7314962B2 (en) * | 2005-04-15 | 2008-01-01 | E. I. Du Pont De Nemours & Co. | Alkylation of aromatic compounds |
| PL1888537T3 (pl) * | 2005-05-26 | 2014-02-28 | Janssen Sciences Ireland Uc | Sposób otrzymywania 4-[(1,6-dihydro-6-okso-2-pirymidynylo)amino benzonitrylu |
| AR065720A1 (es) | 2007-03-14 | 2009-06-24 | Tibotec Pharm Ltd | Polvos para reconstitucion que comprenden rilpivirina dispersos en ciertos polimeros. uso. proceso. |
| EP2175857B1 (en) * | 2007-07-12 | 2013-09-11 | Janssen R&D Ireland | Crystalline form of (e) 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
| WO2012125993A1 (en) | 2011-03-17 | 2012-09-20 | Teva Pharmaceutical Industries Ltd. | Solid state forms of rilpivirine base, and rilipivirine salts |
| AP2013006779A0 (en) * | 2011-04-15 | 2013-03-31 | Emcure Pharmaceuticals Ltd | An improved rilpivirine process |
| US9126949B2 (en) | 2011-04-25 | 2015-09-08 | Hetero Research Foundation | Process for rilpivirine |
| EP2755959B1 (en) * | 2011-09-16 | 2018-05-16 | Hetero Research Foundation | Rilpivirine hydrochloride |
| WO2013170421A1 (zh) * | 2012-05-14 | 2013-11-21 | 上海迪赛诺药业有限公司 | 利匹韦林盐酸盐醇化物多晶型物及其制备方法 |
| WO2013179105A1 (en) * | 2012-06-01 | 2013-12-05 | Laurus Labs Private Limited | Improved process for preparation of rilpivirine and pharmaceutically acceptable salts thereof |
| ES2664094T3 (es) | 2012-07-12 | 2018-04-18 | Hetero Research Foundation | Procedimiento de preparación de rilpivirina utilizando un intermedio nuevo |
| CZ201532A3 (cs) | 2015-01-21 | 2015-02-25 | Zentiva, K.S. | Způsob výroby vysoce čistého Rilpivirinu a jeho solí |
| CN106008366A (zh) * | 2016-05-25 | 2016-10-12 | 山东大学 | 一种利匹韦林的制备方法 |
| ES2970870T3 (es) | 2016-10-24 | 2024-05-31 | Janssen Sciences Ireland Unlimited Co | Composiciones dispersables |
| EP3870568B1 (en) | 2018-10-25 | 2023-06-28 | Minakem | Process for the preparation of rilpivirine |
| CN110526873B (zh) * | 2019-08-15 | 2022-09-16 | 复旦大学 | 氰乙烯基取代的苯并二芳基嘧啶类化合物及其制备方法和用途 |
| WO2021104487A1 (en) | 2019-11-29 | 2021-06-03 | Aptorum Therapeutics Limited | Composition including rilpivirine and use thereof for treating tumors or cancer |
| CN112010810B (zh) * | 2020-09-09 | 2024-01-30 | 瑞阳制药股份有限公司 | 一锅法制备高纯度利匹韦林中间体的方法 |
| CN112778214A (zh) * | 2021-01-13 | 2021-05-11 | 安徽贝克联合制药有限公司 | 用于合成利匹韦林的中间体、其合成方法和利匹韦林的合成方法 |
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| EP0862463A1 (en) | 1995-11-23 | 1998-09-09 | Janssen Pharmaceutica N.V. | Solid mixtures of cyclodextrins prepared via melt-extrusion |
| GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| US6982091B2 (en) | 2001-08-29 | 2006-01-03 | Umd, Inc. | Vaginal delivery of chemotherapeutic agents and inhibitors of membrane efflux systems for cancer therapy |
| DE69943247D1 (de) | 1998-03-27 | 2011-04-14 | Janssen Pharmaceutica Nv | HIV hemmende Pyrimidin Derivate |
| KR100699514B1 (ko) | 1998-03-27 | 2007-03-26 | 얀센 파마슈티카 엔.브이. | Ｈｉｖ를 억제하는 피리미딘 유도체 |
| JP2000035628A (ja) | 1998-07-16 | 2000-02-02 | Konica Corp | ハロゲン化銀写真感光材料 |
| AU5438299A (en) | 1998-08-29 | 2000-03-21 | Astrazeneca Ab | Pyrimidine compounds |
| KR100658489B1 (ko) * | 1998-11-10 | 2006-12-18 | 얀센 파마슈티카 엔.브이. | Ｈｉｖ 복제를 억제하는 피리미딘 |
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| PT1169038E (pt) | 1999-04-15 | 2012-10-26 | Bristol Myers Squibb Co | Inibidores cíclicos da proteína tirosina cinase |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| DE19945982A1 (de) | 1999-09-24 | 2001-03-29 | Knoll Ag | Geschwindigkeitsbestimmte Partikel |
| JP4919566B2 (ja) | 1999-09-24 | 2012-04-18 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗ウイルス組成物 |
| HUP0301117A3 (en) | 2000-02-17 | 2004-01-28 | Amgen Inc Thousand Oaks | Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| AU783981C (en) * | 2000-05-08 | 2007-05-03 | Janssen Pharmaceutica N.V. | HIV replication inhibitors |
| US6596729B2 (en) * | 2000-07-20 | 2003-07-22 | Bristol-Myers Squibb Company | Tricyclic-2-pyridone compounds useful as HIV reverse transcriptase inhibitors |
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| CN1290893C (zh) | 2002-05-03 | 2006-12-20 | 詹森药业有限公司 | 聚合物微乳状液 |
| JP4822707B2 (ja) | 2002-08-09 | 2011-11-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ４−［［４−［［４−（２−シアノエテニル）−２，６−ジメチルフェニル］アミノ］−２−ピリミジニル］アミノ］ベンゾニトリルの製造方法 |
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