Preparation of phenylaminopyrimidine derivatives as inhibitors of BCR-ABL kinase for treating cancer.

Abstract

The present invention relates to novel intermediates useful for the prepn. of novel phenylaminopyrimidine derivs., novel phenylaminopyrimidine derivs., pharmaceutical compn. contg. the novel phenylaminopyrimidine derivs. and processes for their prepn. The invention particularly relates to novel Ph pyrimidine amine derivs. of the general formula I (wherein X is CH or N; n= 1 or 2; R is H or CH3; and Y is absent, S, SO, or SO2). The novel compds. of the invention can be used in the therapy of chronic myeloid leukemia (CML). Since the IC50 values of these mols. are in the range 0.1 to 10.0 nm, these novel compds. are potentially useful for the treatment of CML. The present invention also relates to a particular crystal form of the (3,5-bis trifluoromethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2ylamino)-phenyl]-benzamide (II) , processes for the prepn. thereof, pharmaceutical compns. contg. this crystal form, and their use as antitumor agent in humans. II is also known as AN-019. This invention relates to a process for the prepn. of (3-trifluoromethylsulfonyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2ylamino)-phenyl]-benzamide (III) starting from 4-methyl-2-nitro-aniline through intermediates (3-trifluoromethylsulfonyl)-N-[4-methyl-3-nitrophenyl]-benzamide, (3-trifluoromethylsulfonyl)-N-[3-amino-4-methylphenyl]-benzamide and (3-trifluoromethylsulfonyl)-N-[3-guanidino-4-methylphenyl]-benzamide. This invention also relates to processes for the prepn. of these intermediates. III is also known as AN-024. [on SciFinder(R)]