Trifluoroacetic acid → Diethyl (4-{[4-{[3-(methylsulfinyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

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Reaction Steps

2,4-dichloro-5-(trifluoromethyl)pyrimidine XL was reacted with 1-[3-(methylsulfinyl)phenyl]methanamine hydrochloride (Bioorg. Med. Chem. Lett. 2005, 15, 4136-4142) and diisopropylethylamine at 0° C. overnight to afford a mixture of 2-chloro-N-[3-(methylsulfinyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine and 4-chloro-N-[3-(methylsulfinyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine XLVa/XLVb. A sample of the pure, desired 4-substituted isomer XLVa was isolated as the non-polar component mixture by chromatography over silica gel eluting with 1:3 hexane:ethyl acetate. Reaction of this latter isomer with anilines such as diethyl (4-aminobenzyl)phosphonate in the presence of TFA and TFE under microwave conditions yields the desired product (e.g. diethyl (4-{[4-{[3-(methylsulfinyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, Ex. 47).

Provenance & Evidence