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 PDF

Info

Publication number: NO330013B1
Authority: NO; Norway
Prior art keywords: addition salt; acid addition; formula; amino; stereochemically isomeric
Prior art date: 2002-08-09

Application number

NO20050524A

Other languages

English (en)

Norwegian (no)

Other versions

NO20050524L (no

Inventor

Johannes Josephus Maria Willems

Jan Heeres

Paul Adriaan Jan Janssen

Bart Petrus Anna Maria Jozef Medaer

Didier Philippe Robert Schils

Elisabeth Therese Jeanne Pasquier

Ruben Gerardus George Leenders

Jerome Emile Georges Guillemont

Original Assignee

Janssen Pharmaceutica Nv

Priority date (The priority date 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 date listed.)

2002-08-09

Filing date

2005-02-01

Publication date

2011-02-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=31725448&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO330013(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2005-02-01 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2005-02-01 Publication of NO20050524L publication Critical patent/NO20050524L/no

2011-02-07 Publication of NO330013B1 publication Critical patent/NO330013B1/no

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
239000000460 chlorine Substances 0.000 claims description 12
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
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 6
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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 44
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000243 solution Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 13
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
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239000003446 ligand Substances 0.000 description 8
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 7
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
238000004821 distillation Methods 0.000 description 7
239000012071 phase Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000001632 sodium acetate Substances 0.000 description 7
235000017281 sodium acetate Nutrition 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
239000007795 chemical reaction product Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
238000000605 extraction Methods 0.000 description 6
238000000227 grinding Methods 0.000 description 6
238000002955 isolation Methods 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000012429 reaction media Substances 0.000 description 6
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
208000031886 HIV Infections Diseases 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000003814 drug Substances 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
230000014759 maintenance of location Effects 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
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
ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 4
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FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000356 contaminant Substances 0.000 description 4
239000012467 final product Substances 0.000 description 4
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 4
AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 4
239000002608 ionic liquid Substances 0.000 description 4
229910044991 metal oxide Inorganic materials 0.000 description 4
150000004706 metal oxides Chemical class 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
229910000073 phosphorus hydride Inorganic materials 0.000 description 4
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239000002244 precipitate Substances 0.000 description 4
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QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
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238000003786 synthesis reaction Methods 0.000 description 4
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OLSFRDLMFAOSIA-UHFFFAOYSA-N 2-chloro-1,3,2-dioxaphospholane Chemical compound ClP1OCCO1 OLSFRDLMFAOSIA-UHFFFAOYSA-N 0.000 description 3
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241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
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COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 3
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150000001298 alcohols Chemical class 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
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150000004677 hydrates Chemical class 0.000 description 2
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125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
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239000008194 pharmaceutical composition Substances 0.000 description 2
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AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
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XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
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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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235000019260 propionic acid Nutrition 0.000 description 1
MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical class NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
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PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-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)

NO20050524A 2002-08-09 2005-02-01 Fremgangsmater for fremstillingen av 4-[[4-[[4-(2-cyanoetenyl)-2,6-dimetylfenyl]amino]-2-pyrimidinyl]amino]benzonitril NO330013B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02078306		2002-08-09
PCT/EP2003/050366 WO2004016581A1 (fr)	2002-08-09	2003-08-07	Procedes de preparation de 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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Country Status (25)

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US (3)	US7399856B2 (fr)
EP (1)	EP1529032B1 (fr)
JP (1)	JP4822707B2 (fr)
KR (2)	KR101086678B1 (fr)
CN (4)	CN102702111B (fr)
AR (1)	AR040964A1 (fr)
AU (1)	AU2003266413B2 (fr)
CA (2)	CA2493794C (fr)
CL (1)	CL2010000284A1 (fr)
CY (1)	CY1114428T1 (fr)
DK (1)	DK1529032T3 (fr)
EA (1)	EA007953B1 (fr)
ES (1)	ES2422196T3 (fr)
HR (1)	HRP20050104B1 (fr)
IL (1)	IL166710A (fr)
IS (1)	IS2980B (fr)
MX (1)	MXPA05001541A (fr)
MY (1)	MY144894A (fr)
NO (1)	NO330013B1 (fr)
NZ (1)	NZ538611A (fr)
PL (1)	PL208533B1 (fr)
PT (1)	PT1529032E (fr)
SI (1)	SI1529032T1 (fr)
TW (1)	TWI314146B (fr)
WO (1)	WO2004016581A1 (fr)

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DK1632232T6 (da) *	2004-09-02	2022-04-19	Janssen Pharmaceutica Nv	Salt af 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]¬amino]¬benzonitril
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EP2643294B1 (fr) *	2011-04-15	2016-08-24	Emcure Pharmaceuticals Limited	Procédé perfectionné de préparation de rilpivirine
EP2702044B1 (fr)	2011-04-25	2017-03-22	Hetero Research Foundation	Procédé de préparation de rilpivirine
EP2755959B1 (fr) *	2011-09-16	2018-05-16	Hetero Research Foundation	Chlorhydrate de rilpivirine
WO2013170421A1 (fr) *	2012-05-14	2013-11-21	上海迪赛诺药业有限公司	Polymorphe d'alcoolate de chlorhydrate de rilpivirine et son procédé de préparation
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2003
- 2003-08-07 CN CN201210159781.XA patent/CN102702111B/zh not_active Expired - Lifetime
- 2003-08-07 KR KR1020107026275A patent/KR101086678B1/ko not_active Expired - Lifetime
- 2003-08-07 NZ NZ538611A patent/NZ538611A/en not_active IP Right Cessation
- 2003-08-07 US US10/523,753 patent/US7399856B2/en not_active Expired - Lifetime
- 2003-08-07 CA CA2493794A patent/CA2493794C/fr not_active Expired - Lifetime
- 2003-08-07 PL PL373679A patent/PL208533B1/pl unknown
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- 2003-08-07 HR HRP20050104AA patent/HRP20050104B1/hr not_active IP Right Cessation
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- 2003-08-07 KR KR1020057000881A patent/KR101140785B1/ko not_active Expired - Lifetime
- 2003-08-07 PT PT37878139T patent/PT1529032E/pt unknown
- 2003-08-07 CA CA2686429A patent/CA2686429C/fr not_active Expired - Lifetime
- 2003-08-07 DK DK03787813.9T patent/DK1529032T3/da active
- 2003-08-07 SI SI200332275T patent/SI1529032T1/sl unknown
- 2003-08-07 JP JP2004528518A patent/JP4822707B2/ja not_active Expired - Lifetime
- 2003-08-07 EP EP03787813.9A patent/EP1529032B1/fr not_active Expired - Lifetime
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- 2003-08-07 CN CN2011101114129A patent/CN102225902B/zh not_active Expired - Lifetime
- 2003-08-07 AU AU2003266413A patent/AU2003266413B2/en not_active Expired
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- 2003-08-07 MX MXPA05001541A patent/MXPA05001541A/es active IP Right Grant
- 2003-08-07 WO PCT/EP2003/050366 patent/WO2004016581A1/fr not_active Ceased
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- 2003-08-08 AR ARP030102882A patent/AR040964A1/es active IP Right Grant
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2007
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2008
- 2008-02-14 US US12/031,011 patent/US7705148B2/en active Active
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Also Published As

Publication number	Publication date
CN100554245C (zh)	2009-10-28
AU2003266413A1 (en)	2004-03-03
KR101086678B1 (ko)	2011-11-25
BR0313545B1 (pt)	2021-07-27
PL373679A1 (en)	2005-09-05
IS2980B (is)	2017-09-15
HK1081527A1 (en)	2006-05-19
MY144894A (en)	2011-11-30
IL166710A0 (en)	2006-01-15
CA2493794A1 (fr)	2004-02-26
EP1529032A1 (fr)	2005-05-11
IS7621A (is)	2004-12-29
AU2003266413B2 (en)	2009-04-02
HK1174922A1 (en)	2013-06-21
CA2686429A1 (fr)	2004-02-26
EA200500325A1 (ru)	2005-06-30
PL208533B1 (pl)	2011-05-31
EA007953B1 (ru)	2007-02-27
CN102702111A (zh)	2012-10-03
TWI314146B (en)	2009-09-01
JP4822707B2 (ja)	2011-11-24
CA2686429C (fr)	2010-11-16
CN101481356A (zh)	2009-07-15
JP2005537303A (ja)	2005-12-08
MXPA05001541A (es)	2005-04-19
US20070191407A1 (en)	2007-08-16
US7563922B2 (en)	2009-07-21
IL166710A (en)	2010-12-30
KR101140785B1 (ko)	2012-05-03
DK1529032T3 (da)	2013-07-08
HRP20050104B1 (hr)	2014-02-14
CN102702111B (zh)	2014-12-17
CA2493794C (fr)	2010-05-25
US20080167464A1 (en)	2008-07-10
TW200418810A (en)	2004-10-01
SI1529032T1 (sl)	2013-08-30
KR20050040906A (ko)	2005-05-03
EP1529032B1 (fr)	2013-04-24
HK1129671A1 (en)	2009-12-04
CN102225902A (zh)	2011-10-26
US7705148B2 (en)	2010-04-27
HRP20050104A2 (en)	2006-03-31
CY1114428T1 (el)	2016-08-31
BR0313545A (pt)	2005-07-12
KR20100127889A (ko)	2010-12-06
NO20050524L (no)	2005-02-01
PT1529032E (pt)	2013-07-11
WO2004016581A1 (fr)	2004-02-26
US7399856B2 (en)	2008-07-15
CN102225902B (zh)	2013-04-24
US20060167253A1 (en)	2006-07-27
CL2010000284A1 (es)	2010-08-20
ES2422196T3 (es)	2013-09-09
AR040964A1 (es)	2005-04-27
HK1161869A1 (en)	2012-08-10
CN101481356B (zh)	2012-07-11
NZ538611A (en)	2007-03-30
CN1681774A (zh)	2005-10-12

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Date	Code	Title	Description
2023-09-18	MK1K	Patent expired

Publication	Publication Date	Title
US7705148B2 (en)	2010-04-27	Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
JP2007533764A (ja)	2007-11-22	ロスバスタチンアルキルエーテルを含まないロスバスタチンおよびその塩およびそれらを製造する方法
JP2013040194A (ja)	2013-02-28	４−［（１，６−ジヒドロ−６−オキソ−２−ピリミジニル）アミノベンゾニトリルの製造方法
WO2023167806A1 (fr)	2023-09-07	Procédés et composés utiles dans la synthèse d'un inhibiteur aak1
JP2005531600A (ja)	2005-10-20	ヒトアデノシン−ａ３受容体へのリガンドとしての１，３，５−トリアジン誘導体
US20030069423A1 (en)	2003-04-10	Novel processes for the preparation of adenosine compounds and intermediates thereto
HK1161869B (en)	2013-12-06	Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
HK1129671B (en)	2013-03-28	Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
HK1081527B (en)	2010-05-28	Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
HK1174922B (en)	2015-10-16	Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
NO326697B1 (no)	2009-02-02	Nye 1,3,5-triazinderivater som ligander for humane adenosin-A3-reseptorer, og farmasøytiske sammensetninger som inneholder slike
BRPI0313545B1 (pt)	2021-07-27	Processos para a preparação de 4-[[4-[[4-(2-cianoetenil)-2,6-dimetilfenil]amino]-2-pirimidinil] amino]benzonitrila
JPH05255255A (ja)	1993-10-05	６−ｎ−置換アミノピコリン酸誘導体及びその製造法