反应详情

Reaction of 2,4-dichloro-5-(trifluoromethyl)pyrimidine XL with N-[3-(aminomethyl)pyridin-2-yl]-N-methylmethanesulfonamide (WO2007/072158, WO2008/115369) in the presence of diisopropylethylamine affords a solution of N-[3-({[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}methyl)pyridin-2-yl]-N-methylmethanesulfonamide XLIa and its regioisomer N-[3-({[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}methyl)pyridin-2-yl]-N-methylmethanesulfonamide XLIb. On larger scales stirring at 0° C., precipitation of the pure 4-substituted isomer XLIa occurs. Reaction of a sample of the pure mixture of N-[3-({[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}methyl)pyridin-2-yl]-N-methylmethanesulfonamide with anilines such as 4-[(diethylphosphoryl)methyl]aniline in the presence of TFA and TFE under microwave irradiation yields 2-substituted N-methyl-N-[3-({[5-(trifluoromethyl)pyrimidin-4-yl]amino}methyl)pyridin-2-yl]methanesulfonamides (e.g. N-[3-({[2-({4-[(diethylphosphoryl)methyl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}methyl)pyridin-2-yl]-N-methylmethanesulfonamide, Example 10).