反应详情

温度

117 °C

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]+.

1. temperatureto cool to room temperature
2. customhad been consumed
3. stirringthe reaction mixture was stirred for 24 hours at 117° C
4. filtrationThe formed solid was filtered
5. additionTo the aqueous layer, 6N HCl was added dropwise until the pH=4
6. customA precipitate was formed
7. extractionto extract the compound
8. extractionThen a solution of 10% isopropanol in CH2Cl2 (100 mL) was used for the extraction
9. waitafter sitting for 30 minutes
10. customa significant amount of solid was formed
11. filtrationThe white solid was filtered
12. washwashed with water
13. customdried