(Diethylamino)sulfur trifluoride → HCID 67973808, compound

Participants

Reaction Steps

DAST (0.02 mL, 0.15 mmol) was added dropwise to a solution of (rac)-5-(2-hydroxy-propyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (30 mg, 0.1 mmol) in DCM (0.6 mL) at 0° C. The mixture was then allowed to warm to room temperature and stirred at 100° C. for 10 minutes under microwave irradiation. The mixture was quenched with a saturated solution of NaHCO3 and extracted with DCM. 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 0/100 to 100/0). Desired fractions were collected and solvents evaporated in vacuo. The product was repurified by RP HPLC on (C18 XBridge 30×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 100% ACN) and triturated with DIPE to yield (rac)-5-(2-fluoro-propyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (8.3 mg, 29% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.38 (dd, J=24.0, 6.5 Hz, 3H), 3.42 (ddd, J=20.1, 14.6, 7.6 Hz, 1H), 3.80-3.91 (m, 1H), 3.91-4.08 (m, 2H), 4.33-4.46 (m, 2H), 4.83-5.05 (m, 1H), 5.10 (s, 2H), 6.90-6.95 (m, 1H), 6.95-7.03 (m, 3H), 7.27-7.33 (m, 2H).

Provenance & Evidence