反应详情

Reaction of 2,4-dichloro-5-(trifluoromethyl)pyrimidine XL with commercially available 2-amino-N-methyl-benzamide and diisopropylethylamine at room temperature overnight affords a mixture of 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide and 2-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-N-methylbenzamide (XLIIIa/XLIII b). Trituration of the mixture with methylene chloride affords a pure sample of the desired 4-substitiuted product XLIIIa. Concentration of the mother liquors and purification of the residue by chromatography over silica gel using 5% EtOAc in methylene chloride as eluent isolating the less polar material affords further pure 4-substituted isomer plus a mixture of isomers which may be subjected to further chromatography if desired. Reaction of pure 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide XLIIIa with anilines such as diethyl (4-aminobenzyl)phosphonate in the presence of TFA and TFE under microwave irradiation yields the desired products (e.g. diethyl (4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, Ex. 20)

1. customaffords
2. customConcentration of the mother liquors and purification of the residue by chromatography over silica gel using 5% EtOAc in methylene chloride as eluent
3. customisolating the less polar material
4. customaffords further pure 4-substituted isomer
5. additiona mixture of isomers which
6. customunder microwave irradiation
7. customyields the desired products (e.g. diethyl (4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, Ex. 20)