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Decarboxylative Csingle bondC cross-couplings of 2-aminopyrimidine-5-carboxylic acids under a Pd/Ag-based catalytic system opens a new platform for introducing diverse C5 substituents. The reaction methods proceeded efficiently with various acids and the coupling partners of aryl iodides, alkenes, bromoalkynes, and azoles.

General procedure for the synthesis of 2-aminopyrimidine-5-carboxylic acid from methyl 2-aminopyrimidine-5-carboxylate: methyl 2-aminopyrimidine-5-carboxylate (300 mg, 2.0 mmol) was dissolved in methanol (5 mL) containing a small amount of water. Lithium hydroxide (122 mg, 5.1 mmol) was added to the solution and the reaction mixture was subsequently stirred at 60 °C overnight. Upon completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was diluted with water and the pH was adjusted to 4 with 1 M HCl solution.At this point, 2-aminopyrimidine-5-carboxylic acid precipitated as a white solid, and the product was collected by filtration under vacuum to give 244 mg in 90% yield. The product was characterized by 1H NMR (DMSO-d6): δ 12.73 (1H, broad peak), 8.63 (2H, single peak), 7.44 (2H, broad peak).

[1] Ngoc Son Le Pham . “Decarboxylative cross-couplings of 2-aminopyrimidine-5-carboxylic acids.” Tetrahedron 74 28 (2018): Pages 3843-3851.