2-Amino-4,6-dichloropyrimidine → (3S,6R)-1-[2-amino-6-(1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 4,6-dichloro-2-pyrimidinamine (0.2 g, 1.22 mmol), (3S,6R)-6-methyl-3-piperidinecarboxylic acid (0.265 g, 1.342 mmol) and NaHCO3 (V, 6.10 mmol) in 1,4-dioxane (10 mL) and water (5 mL) was stirred overnight at 117° C. into a sealed tube. The reaction was allowed to cool to room temperature. LCMS showed that most of the starting material 4,6-dichloro-2-pyrimidinamine had been consumed. Then 1H-indazole-6-boronic acid pinacol ester (0.327 g, 1.342 mmol) and Pd(Ph3P)4 (0.028 g, 0.024 mmol) were added, and the reaction mixture was stirred for 24 hours at 117° C. The mixture was poured into water (200 mL). The formed solid was filtered. To the aqueous layer, 6N HCl was added dropwise until the pH=4. A precipitate was formed and the solution looked cloudy. A solution of 10% isopropanol in EtOAc (200 mL) was used to extract the compound, but most of the compound stayed in water. This organic layer was discarded. Then a solution of 10% isopropanol in CH2Cl2 (100 mL) was used for the extraction. The mixture turned cloudy after sitting for 30 minutes, and a significant amount of solid was formed. The white solid was filtered, washed with water, and dried to afford the title compound (95 mg) as a white solid. LC-MS (ES) m/z=353 [M+H]+.

Provenance & Evidence