4-Aminoacetanilide → N-[4-(3,5-dichloro-2,6-difluoro-pyridin-4-ylamino)-phenyl]-acetamide

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Reaction Steps

3,5-Dichloro-2,4,6-trifluoro-pyridine (136) (1 g, 4.95 mmol) and N-(4-Amino-phenyl)-acetamide (137) (0.743 g, 4.95 mmol) were dissolved in NMP (12 mL), iPr2EtN (9.9 mmol) was added and the mixture was shaken at room temperature for 5 hours. TLC and LC-MS indicated complete reaction at this point. The mixture was diluted with EtOAc (50 mL), washed with NaHCO3 (aqueous sat., 50 mL) and passed through a plug of silica gel to remove any baseline impurities. Upon concentration, the desired product (138) precipitated as a beige/pink powder that was collected by filtration under reduced pressure followed by drying under high vacuum for 16 h (1.43 g, 2.88 mmol, 58% yield). LC-MS (ESI): (exact mass: 331.01) m/e=332.1 [M+1]+ (100%), 664.9 [2M+1]+ (30%), 996.2 [3M+1]+ (10%). 1H NMR (400 MHz, DMSO-d6): δ 2.03 (s, 3H), 6.99 (d, 2H, J=7.2 Hz), 7.49 (d, 2H, J=6.8 Hz), 9.00 (s, 1H), 9.89 (s, 1H). 19F NMR (400 MHz, DMSO-d6): δ−76.55 (TFA reference), −75.89 (s, 2F).

Provenance & Evidence