反应详情

温度

0 °C

6-chloro-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.410 g, 1.3 mmol) in DMF (4 mL) was added portionwise to sodium hydride (60% dispersion in oil) (0.063 g, 1.56 mmol) in DMF (2 mL) cooled to 0° C. over a period of 2 minutes under nitrogen and stirred for 25 minutes. Methyl iodide (0.069 ml, 1.1 mmol) was added in one portion and the suspension was warmed and stirred at 20° C. for 72 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride (5 mL) then diluted with EtOAc (50 mL), and washed sequentially with water (10 mL) and saturated brine (10 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 6-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.422 g, 99%) as a colourless clear gum.

1. temperaturethe suspension was warmed
2. stirringstirred at 20° C. for 72 hours
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (5 mL)
4. additionthen diluted with EtOAc (50 mL)
5. washwashed sequentially with water (10 mL) and saturated brine (10 mL)
6. dry with materialThe organic layer was dried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customto afford crude product
10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
11. customPure fractions were evaporated to dryness