反应详情

温度

70 °C

A solution of 5-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide from Example 60 (0.5 g, 1.32 mmol) in 30 mL of dimethylformamide was treated with excess ethyl bromoacetate (0.7 mL, 6.60 mmol). After heating at 70° C. for 1 h, triethylamine (0.9 ml, 6.6 mmol) was added dropwise; the reaction mixture was then heated at 70° C. for an additional 30 min, after which it was partitioned between saturated sodium bicarbonate and dichloromethane. The organic extract was concentrated in vacuo, and the residue was applied to a 10 g SCX column which was washed with methanol and eluted with 1 N ammonia in methanol. The yellow fractions were combined and concentrated in vacuo to afford an orange oil, which was subjected to silica gel chromatography. Elution with 9:1 dichloromethane-methanol, then 9:3 dichloromethane-methanol provided 0.31 g (51%) of the title compound as a yellow solid.

1. temperaturethe reaction mixture was then heated at 70° C. for an additional 30 min
2. customafter which it was partitioned between saturated sodium bicarbonate and dichloromethane
3. extractionThe organic extract
4. concentrationwas concentrated in vacuo
5. washwas washed with methanol
6. washeluted with 1 N ammonia in methanol
7. concentrationconcentrated in vacuo
8. customto afford an orange oil, which
9. washElution with 9:1 dichloromethane-methanol