反应详情

温度

-40 °C

To a solution of 0.500 g (2.06 mmol) of 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-α]azepin-4-one (step 4.1) in dry tetrahydrofuran (20 mL) under argon at −40° C. was added 2.48 mL (2.48 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −40° C. for 10 min and 0.636 g of 4-fluoro-2-methoxy-benzaldehyde (4.13 mmol) diluted in 5 ml of dry tetrahydrofuran was added. The reaction was allowed to increase to room temperature for 2 h. The mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with dichloromethane. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia) to afford 0.505 g of a white solid (62%).

1. additionwas added
2. temperatureto increase to room temperature for 2 h
3. customThe mixture was quenched with the addition of a saturated solution of ammonium chloride
4. extractionextracted with dichloromethane
5. dry with materialThe organic phase was dried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia)