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PE20070114A1 - TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION - Google Patents

TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION

Info

Publication number
PE20070114A1
PE20070114A1 PE2006000657A PE2006000657A PE20070114A1 PE 20070114 A1 PE20070114 A1 PE 20070114A1 PE 2006000657 A PE2006000657 A PE 2006000657A PE 2006000657 A PE2006000657 A PE 2006000657A PE 20070114 A1 PE20070114 A1 PE 20070114A1
Authority
PE
Peru
Prior art keywords
trifluoro
pirazin
react
phenyl
give
Prior art date
Application number
PE2006000657A
Other languages
Spanish (es)
Inventor
David Michael Blum
Yanzhong Wu
Timothy John Doyle
Jay Thomas Afragola
Jean Schmid
Original Assignee
Wyeth Corp
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37074929&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PE20070114(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Wyeth Corp filed Critical Wyeth Corp
Publication of PE20070114A1 publication Critical patent/PE20070114A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

SE REFIERE AL COMPUESTO HEMIFUMARATO DE 6-CLORO-5-{2,6-DIFLUORO-4-[3-(METILAMINO)PROPOXI]FENIL}-2-PIRAZIN-2-IL-N-[(1S)-2,2,2-TRIFLUORO-1-METILETIL]PIRIMIDIN-4-AMINA Y SU PROCEDIMIENTO DE PREPARACION QUE CONSISTE EN: A) HACER REACCIONAR UN PIRAZINO-2-CARBONITRILOEN UNA BASE A EN UN ALCOHOL Y TRATAR CON UNA SAL DE AMONIO DE UN ACIDO INORGANICO PARA DAR UNA SAL DE ACIDO PIRAZINO-2-CARBOXIAMIDINA INORGANICA (A); B) HACER REACCIONAR (A) CON UN ESTER DE ACIDO MALONICO DE FORMULA I, DONDE R1 Y R2 SON CADA UNO ALQUILO C1-C3 EN UN SOLVENTE APROTICO EN PRESENCIA DE UNA BASE Y ACIDIFICAR PARA OBTENER 2-PIRAZIN-2-IL-5-(2,4,6-TRIFLUORO-FENIL)-PIRIMIDINO-4,6-DIOL (B); C) CLORINAR (B) CON OXICLORURO FOSFOROSO COMO REACTIVO DE CLORINACION EN PRESENCIA DE UNA AMINA BASE EN UN SOLVENTE APROTICO PARA DAR 4,6-DICLORO-2-PIRAZIN-2-IL-5-(2,4,6-TRIFLUORO-FENIL)-PIRIMIDINA (C); D) HACER REACCIONAR (C) CON (S)-2,2,2-TRIFLUORO-1-METIL-ETILAMINA EN UN SOLVENTE APROTICO PARA DAR 6-CLORO-2-PIRAZIN-2-IL-N-[(1S)-2,2,2-TRIFLUORO-1-METILETIL]-5-(2,4,6-TRIFLUOROFENIL)PIRIMIDIN-4-AMINA (D); E) HACER REACCIONAR 3-METILAMINO-PROPAN-1-OL CONBASE BEN UN SOLVENTE APROTICO Y ADICIONAR (D) PARA DAR 6-CLORO-5-{2,6-DIFLUORO-4-[3-(METILAMINO)PROPOXI]FENIL}-2-IL-N-[(1S)-2,2,2-TRIFLUORO-1-METILETIL]PIRIMIDIN-4-AMINA (E); F) HACER REACCIONAR (E) EN UN SOLVENTE APROTICO CON ACIDO FUMARICO EN UN ALCOHOL PARA OBTENER DICHO HEMIFUMARATO, EL CUAL ES UN INHIBIDOR DE TUBULINA UTIL EN EL TRATAMIENTO DE CANCERREFERS TO THE HEMIFUMARATE COMPOUND OF 6-CHLORO-5- {2,6-DIFLUORO-4- [3- (METHYLAMINO) PROPOXI] PHENYL} -2-PIRAZIN-2-IL-N - [(1S) -2.2 , 2-TRIFLUORO-1-METHYLETHYL] PYRIMIDIN-4-AMINE AND ITS PREPARATION PROCEDURE WHICH CONSISTS OF: A) REACTING A PIRAZINE-2-CARBONITRILE IN A BASE IN AN ALCOHOL AND TREATING WITH AN AMMONIUM SALT OF AN INORGANIC ACID TO GIVE A SALT OF INORGANIC PIRAZINE-2-CARBOXIAMIDINE ACID (A); B) REACT (A) WITH AN ESTER OF MALONIC ACID OF FORMULA I, WHERE R1 AND R2 ARE EACH C1-C3 ALKYL IN AN APROTICAL SOLVENT IN THE PRESENCE OF A BASE AND ACIDIFY TO OBTAIN 2-PIRAZIN-2-IL-5 - (2,4,6-TRIFLUORO-PHENYL) -PYRIMIDINE-4,6-DIOL (B); C) CHLORINATING (B) WITH PHOSPHORUS OXYCHLORIDE AS A CHLORINATING REAGENT IN THE PRESENCE OF A BASE AMINE IN AN APROTICAL SOLVENT TO GIVE 4,6-DICHLORO-2-PIRAZIN-2-IL-5- (2,4,6-TRIFLUORO- PHENYL) -PYRIMIDINE (C); D) REACT (C) WITH (S) -2,2,2-TRIFLUORO-1-METHYL-ETHYLAMINE IN AN APROTICAL SOLVENT TO GIVE 6-CHLORO-2-PIRAZIN-2-IL-N - [(1S) - 2,2,2-TRIFLUORO-1-METHYLETHYL] -5- (2,4,6-TRIFLUOROPHENYL) PYRIMIDIN-4-AMINE (D); E) REACT 3-METHYLAMINE-PROPAN-1-OL WITH BASED BEN AN APROTIC SOLVENT AND ADD (D) TO GIVE 6-CHLORINE-5- {2,6-DIFLUORO-4- [3- (METHYLAMINE) PROPOXI] PHENYL} -2-IL-N - [(1S) -2,2,2-TRIFLUORO-1-METHYLETHYL] PYRIMIDIN-4-AMINE (E); F) REACT (E) IN AN APROTIC SOLVENT WITH FUMARIC ACID IN AN ALCOHOL TO OBTAIN SAID HEMIFUMARATE, WHICH IS A USEFUL INHIBITOR OF TUBULIN IN THE TREATMENT OF CANCER

PE2006000657A 2005-06-13 2006-06-13 TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION PE20070114A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US69001605P 2005-06-13 2005-06-13
US80278106P 2006-05-24 2006-05-24

Publications (1)

Publication Number Publication Date
PE20070114A1 true PE20070114A1 (en) 2007-02-03

Family

ID=37074929

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2006000657A PE20070114A1 (en) 2005-06-13 2006-06-13 TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION

Country Status (12)

Country Link
EP (1) EP1891052A1 (en)
JP (1) JP2008543838A (en)
AR (1) AR054392A1 (en)
AU (1) AU2006259663A1 (en)
BR (1) BRPI0612145A2 (en)
CA (1) CA2610416A1 (en)
GT (1) GT200600257A (en)
MX (1) MX2007015718A (en)
PE (1) PE20070114A1 (en)
SV (1) SV2007002573A (en)
TW (1) TW200716613A (en)
WO (1) WO2006138180A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011057805A1 (en) 2009-11-12 2011-05-19 R&D Biopharmaceuticals Gmbh Tubulin inhibitors
US9649317B2 (en) * 2012-09-19 2017-05-16 The Trustees Of The University Of Pennsylvania Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies
WO2017181974A1 (en) * 2016-04-20 2017-10-26 苏州苏领生物医药有限公司 Five-membered heterocyclic compound, preparation method therefor, pharmaceutical composition and use
US11623927B2 (en) 2018-03-02 2023-04-11 The Trustees Of The University Of Pennsylvania Substituted [1,2,4]triazolo[1,5-a]pyrimidines for stabilizing microtubules

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE432077T1 (en) * 2003-09-24 2009-06-15 Wyeth Corp 5-ARYLPYRIMIDINE AS AN ANTI-CANCER AGENT
WO2005030775A1 (en) * 2003-09-24 2005-04-07 Wyeth Holdings Corporation 6-[(substituted)phenyl]triazolopyrimidines as anticancer agents

Also Published As

Publication number Publication date
CA2610416A1 (en) 2006-12-28
EP1891052A1 (en) 2008-02-27
TW200716613A (en) 2007-05-01
BRPI0612145A2 (en) 2010-10-19
AU2006259663A1 (en) 2006-12-28
JP2008543838A (en) 2008-12-04
SV2007002573A (en) 2007-01-03
AR054392A1 (en) 2007-06-20
GT200600257A (en) 2007-02-14
WO2006138180A1 (en) 2006-12-28
MX2007015718A (en) 2008-02-21

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