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0 °C

A solution of (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.135 g, 0.36 mmol) in THF (0.5 mL) was added to a suspension of a 60% dispersion of sodium hydride in mineral oils (17 mg, 0.44 mmol) in THF (0.5 mL) at 0° C. The mixture was stirred for 10 minutes at 0° C., then iodomethane (0.046 mL, 0.73 mmol) was added. The reaction was heated at 120° C. for 10 minutes under microwave irradiation. Then the mixture was quenched with a saturated solution of NH4Cl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The residue was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). Desired fractions were collected and the solvents evaporated in vacuo. The residue was triturated with DIPE to yield (S)-5-(4-fluoro-phenyl)-6-methoxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (90 mg, 64% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 3.26 (s, 3H), 3.36 (t, J=9.2 Hz, 1H), 3.51 (dd, J=9.5, 3.9 Hz, 1H), 4.21 (dtd, J=9.0, 4.5, 4.5, 2.3 Hz, 1H), 4.59 (dd, J=13.3, 4.7 Hz, 1H), 4.74 (dd, J=13.3, 2.2 Hz, 1H), 5.13 (s, 2H), 6.94-7.00 (m, 1H), 7.00-7.04 (m, 3H), 7.10-7.19 (m, 2H), 7.27-7.36 (m, 4H).

1. temperatureThe reaction was heated at 120° C. for 10 minutes under microwave irradiation
2. customThen the mixture was quenched with a saturated solution of NH4Cl
3. extractionextracted with AcOEt
4. customThe organic layer was separated
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customthe solvents evaporated in vacuo
8. customThe residue was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
9. customDesired fractions were collected
10. customthe solvents evaporated in vacuo
11. customThe residue was triturated with DIPE