反应详情

A solution of N-(4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyphenyl)formamide (Preparation 55, 37 mg, 0.151 mmol) in THF (1 mL) was treated with sodium hydride (10 mg, 0.250 mmol) at 0° C. After stirring for 20 minutes at room temperature, the mixture was cooled to 0° C. and 8-(1-methyl-1H-pyrazol-4-yl)-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 35, 50 mg, 0.173 mmol) was added. The reaction was allowed to reach room temperature and stirred for 18 hours. Aqueous NaOH (2M, 0.5 mL) and MeOH (0.5 mL) were added and the resulting mixture stirred at room temperature for 1 hour. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, dried and evaporated. The residue was purified by silica gel column chromatography eluting with 0 to 10% MeOH in EtOAc to give the title compound (9 mg, 14%).

1. temperaturethe mixture was cooled to 0° C.
2. customto reach room temperature
3. stirringstirred for 18 hours
4. stirringthe resulting mixture stirred at room temperature for 1 hour
5. customThe volatiles were removed under reduced pressure
6. customthe residue was partitioned between EtOAc and water
7. extractionThe aqueous layer was extracted with EtOAc
8. washthe combined organic layers were washed with water, brine
9. customdried
10. customevaporated
11. customThe residue was purified by silica gel column chromatography
12. washeluting with 0 to 10% MeOH in EtOAc