Cesium carbonate → 3-({4-[(Dimethylamino)carbonyl]phenyl} amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid

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Reaction Steps

To a dry 100 mL flask under a nitrogen atmosphere was added ethyl 3-amino-5-(4-fluorobenzyl)pyridine-2-carboxylate (89 mg, 0.325 mmol) described in example 1, Cs2CO3 (148 mg, 0.455 mmol), Pd2dba3 (1.5 mg, 0.0016 mmol), and Xantphos (2.8 mg, 0.0049 mmol). Dioxane (15 mL) and 4-amino-N,N-dimethylbenzamide (1.25 mL of a 0.78 M solution in dioxane, 0.975 mmol) were added and the resulting solution was refluxed for 2 hrs. Sodium tert-butoxide (94 mg, 0.975 mmol) was added and the mixture was stirred for 10 minutes. The mixture was cooled to ambient temperature, diluted with dichloromethane, filtered through Celite and concentrated under reduced pressure. Water was added and the aqueous layer was washed with ethyl acetate and then acidified with 1 N hydrochloric acid to a pH of 4. The resulting yellow precipitate was collected by vacuum filtration to yield 3-({4-[(dimethylamino)carbonyl]phenyl}amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid (120 mg, 94% yield). 1H NMR (CDCl3) δ 7.82 (s, 1 H), 7.46 (s, 1 H), 7.38 (d, J=8.4 Hz, 2 H), 7.13 (d, J=8.4 Hz, 2 H), 7.09-7.05 (m, 2 H), 6.97-6.93 (m, 2 H), 3.88 (s, 2 H), 3.07 (s, 3 H), 2.99 (s, 3 H); MS m/z 392 (M−1).

Provenance & Evidence