反应详情

温度

70 °C

In a 5 L 4-necked flask with an overhead mechanical stirrer was added 5-chloro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation J; 34.83 g, 149.1 mmol), tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-Pyrazol-1-yl)azetidine-1-carboxylate (Preparation F; 86.82 g, 223.6 mmol), and K3PO4 (94.92 g, 447.2 mmol) by powder funnel. Dioxane (745.3 mL, 149.1 mmol) was added to rinse down funnel. Pd(PPh3)4 (17.23 g, 14.91 mmol) was added, followed by 74.5 mL of water. The reaction mixture was slowly heated to 70° C. as measured by an internal temperature probe. After heating for 6 hours, the reaction mixture was cooled to ambient temperature. The reaction mixture was diluted in EtOAc (500 mL) and water (100 mL), and then the resultant solids were filtered out. The solids were washed with EtOAc (2×500 mL) to afford a grey-white solid, which was re-introduced back to the 5 L 4-neck flask and diluted with 1 L of water and 300 mL of EtOAc. This was stirred for 3 hours, and then the solids were isolated by filtration. After washing with EtOAc (2×500 mL), the solids were dried to afford tert-butyl 3-(cyanomethyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (60.83 g, 132.4 mmol, 88.81% yield). MS (apci) m/z=460.1 (M+H).

1. washto rinse down funnel
2. temperatureAfter heating for 6 hours
3. temperaturethe reaction mixture was cooled to ambient temperature
4. filtrationwater (100 mL), and then the resultant solids were filtered out
5. washThe solids were washed with EtOAc (2×500 mL)
6. customto afford a grey-white solid, which
7. additionwas re-introduced back to the 5 L 4-neck flask
8. customthe solids were isolated by filtration
9. washAfter washing with EtOAc (2×500 mL)
10. customthe solids were dried