反应详情

Reaction of 2,4-dichloro-5-(trifluoromethyl)pyrimidine XL with commercially available 1-[3-(methylsulfonyl)phenyl]methanamine and diisopropylethylamine at 0° C. overnight affords a mixture of 2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine and 4-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine XLIVa/XLIVb. The crude mixture was crystallized from methylene chloride to afford a sample of the pure, undesired 2-substituted isomer XLIVb. The mother liquors were chromatographed over silica gel eluting with 1:1 hexane:ethyl acetate to yield a further pure sample of the 2-substituted isomer plus a sample of the desired 2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine XLIVa. Reaction of this latter isomer with anilines such as diethyl (4-aminobenzyl)phosphonate in the presence of TFA and TFE under microwave irradiation yields the desired product (e.g. diethyl (4-{[4-{[3-(methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, Ex. 25).

1. customaffords
2. customThe crude mixture was crystallized from methylene chloride
3. customto afford a sample of the pure, undesired 2-substituted isomer XLIVb
4. customThe mother liquors were chromatographed over silica gel eluting with 1:1 hexane
5. customethyl acetate to yield a further pure sample of the 2-substituted isomer
6. customunder microwave irradiation