Process for the preparation of dasatinib and its intermediates
The present invention relates to processes for the preparation of dasatinib and its intermediates.
1. A process for the preparation of a compound of Formula 1a or a salt thereof
which comprises reacting a compound of Formula 2a or a salt thereof with a compound of Formula 3,
wherein R 1 and R 2 are independently selected from the group consisting of hydrogen, amino protecting group, 6-chloro-2-methyl-pyrimidin-4-yl, and 6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl; and R 3 is independently selected from the group consisting of C 1 -C 6 alkyl, C 6 -C 12 aryl, C 7 -C 12 arylalkyl, and C 7 -C 12 alkylaryl.
2. The process according to claim 1 , wherein reacting the compound of Formula 2a or a salt thereof with the compound of Formula 3 is performed in one or more solvents at a temperature of 15° C. to 40° C.
3. The process according to claim 1 , wherein the compound of Formula 3 is prepared in situ by combining 2-chloro-6-methylaniline with ethyl magnesium bromide in one or more solvents at a temperature of −10° C. to 10° C.
4. The process according to claim 3 , wherein the solvent is selected from the group consisting of water, aromatic hydrocarbons, esters, halogenated hydrocarbons, ketones, ethers, polar aprotic solvents, and mixtures thereof.
5. The process according to claim 2 , wherein the solvent is selected from the group consisting of water, aromatic hydrocarbons, esters, halogenated hydrocarbons, ketones, ethers, polar aprotic solvents, and mixtures thereof.