http://rdf.ncbi.nlm.nih.gov/pubchem/patent/PE-20070114-A1

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inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_eb54c80355b2505f72019786ff33d94c
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publicationDate 2007-02-03-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber PE-20070114-A1
titleOfInvention TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION
abstract REFERS 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
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