2-AMINO-N-(2-CHLORO-6-METHYLPHENYL) THIAZOLE 5 CARBOXAMIDE SALT AND ITS USE TO PREPARE PURE N-(2-CHLORO-6-METHYLPHENYL)-2-[[6-[4-(2-HYDROXYETHYL)-1-PIPERAZINYL]-2-METHYL-4-PYRIMIDINYL]AMINO]-5-THIAZOLE CARBOXAMIDE
Publication Date: 2009-Feb-12
The IP.com Prior Art Database
2-AMINO-N-(2-CHLORO-6-METHYLPHENYL) THIAZOLE 5 CARBOXAMIDE SALT AND ITS USE TO PREPARE PURE N-(2-CHLORO- 6-METHYLPHENYL)-2-[[6-[4-(2-HYDROXYETHYL)-1-PIPERAZINYL]-2- METHYL-4-PYRIMIDINYL]AMINO]-5-THIAZOLE CARBOXAMIDE
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2- methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide( referred as "DASA"), a compound having the following chemical structure:
also known as BMS-354825, is a drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel®.It is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is also being assessed for use in metastatic melanoma.
DAS- 5 is purified by converting it to DAS-5 salt and then converting back the salt to a free base form.
The DAS-5 salt can be prepared by a process comprising reacting DAS-5 with an acid, and recovering the acid salt of DAS-5.
Preferably, when the acid is PTSA, said reaction comprises a) dissolving DAS-5 and PTSA to obtain a solution, b) precipitating DAS-5-PTSA salt to obtain a suspension, and c) recovering said salt from the suspension.
Preferably, DAS-5 and PTSA are dissolved in an organic solvent. Preferably the organic solvent is an alcohol. More preferably, the alcohol is a C1-4 alcohol, most preferably ethanol.
Preferably, dissolution is achieved by heating, which also facilitates the reaction between DAS-5 and PTSA. Preferably, heating is done to about reflux temperature.