反应详情

温度

117 °C

A mixture of 4,6-dichloro-2-pyrimidinamine (3 g, 18.3 mmol), (3S,6R)-6-methyl-3-piperidinecarboxylic acid (3.98 g, 20.12 mmol), and NaHCO3 (7.68 g, 91 mmol) in 1,4-dioxane (100 mL) and water (50 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 4-cyano-3-fluorobenzeneboronic acid (3.32 g, 20.12 mmol) and Pd(Ph3P)4 (0.423 g, 0.366 mmol) were added, and the reaction mixture was stirred for 24 hours at 117° C. The mixture was poured into water (300 mL) and EtOAc (200 mL). At this moment the pH of the solution was 9. The compound stayed in the water layer. The water layer was separated from the organic layer. There was some black colored and yellow colored suspension in the water layer, which was filtered out. (They were not product). To the aqueous layer, 6N HCl was added dropwise to make the pH=4. A precipitate was formed. The precipitate was filtered, washed with water, and dried to afford the title compound (3.6 g) as a light yellow solid. LC-MS (ES) m/z=356 [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. customThe water layer was separated from the organic layer
5. filtrationwas filtered out
6. additionTo the aqueous layer, 6N HCl was added dropwise
7. customA precipitate was formed
8. filtrationThe precipitate was filtered
9. washwashed with water
10. customdried