反应详情

温度

0 °C

A 60% dispersion of sodium hydride in mineral oils (9 mg, 0.22 mmol) was added to a stirred solution of 2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.05 g, 0.20 mmol) in DMF (3 mL) at 0° C. The mixture was stirred at 0° C. for 15 minutes. Then iodomethane (15 μL, 0.24 mmol) was added at 0° C., the mixture stirred at 0° C. for 1 hour and allowed to warm to room temperature. Then additional iodomethane (15 μL, 0.24 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was treated with a saturated solution of NH4Cl and the solvents evaporated in vacuo. The crude product was diluted with H2O and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-methyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (49 mg, 97% yield) as an oil which solidified upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 3.14 (s, 3H), 3.69-3.83 (m, 2H), 4.32-4.49 (m, 2H), 5.09 (s, 2H), 6.93 (s, 1H), 6.96 (t, J=7.2 Hz, 1H), 6.99 (d, J=8.1 Hz, 2H), 7.27-7.32 (m, 2H).

1. stirringthe mixture stirred at 0° C. for 1 hour
2. temperatureto warm to room temperature
3. stirringthe mixture was stirred at room temperature overnight
4. customthe solvents evaporated in vacuo
5. additionThe crude product was diluted with H2O
6. extractionextracted with DCM
7. customThe organic layer was separated
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customthe solvents evaporated in vacuo
11. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60)
12. customThe desired fractions were collected
13. customthe solvents evaporated in vacuo