反应详情

DAST (0.067 mL, 0.55 mmol) was added to a solution of (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (135 mg, 0.37 mmol) in DCM (2 mL) at −10° C. The mixture was stirred at room temperature for 15 minutes. Then quenched with a 1N solution of HCl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue was purified by flash column chromatography (silica; AcOEt in heptane 20/80 to 80/20). Desired fractions were collected and the solvents evaporated in vacuo. The residue was triturated with DIPE to yield (S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (81 mg, 60% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.32-4.37 (m, 1H), 4.37-4.42 (m, 0.5H), 4.42-4.52 (m, 1H), 4.59 (dd, J=9.4, 4.5 Hz, 0.5H), 4.66-4.77 (m, 2H), 5.13 (s, 2H), 6.95-7.03 (m, 3H), 7.03 (s, 1H), 7.13-7.20 (m, 2H), 7.27-7.35 (m, 4H).

1. customThen quenched with a 1N solution of HCl
2. extractionextracted with AcOEt
3. customThe organic layer was separated
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. customthe solvent evaporated in vacuo
7. customThe residue was purified by flash column chromatography (silica; AcOEt in heptane 20/80 to 80/20)
8. customDesired fractions were collected
9. customthe solvents evaporated in vacuo
10. customThe residue was triturated with DIPE