2-Chloropyridine → 5-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

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Reaction Conditions

Reaction Steps

Palladium (II) acetate (9 mg, 0.038 mmol) was added to a stirred suspension of 5-(4-fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.74 g, 2.83 mmol), 2-chloropyridine (0.4 mL, 4.25 mmol), cesium carbonate (1.84 g, 5.66 mmol) and (2-biphenylyl)di-tert-butylphosphine (0.17 g, 5.66 mmol) in toluene (15 mL) in a sealed tube and under nitrogen. The mixture was stirred at 120° C. for 16 hours, then filtered through a pad of diatomaceous earth and washed with AcOEt. The solvents were evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0). The desired fractions were collected, the solvents evaporated in vacuo and triturated with DIPE to yield 5-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (620 g, 65% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.12-4.20 (m, 2H), 4.54 (dd, J=6.9, 5.1 Hz, 2H), 5.44 (s, 2H), 6.81 (d, J=8.6 Hz, 1H), 6.90 (ddd, J=7.1, 5.2, 0.7 Hz, 1H), 7.03 (s, 1H), 7.08-7.17 (m, 2H), 7.28-7.35 (m, 2H), 7.55-7.63 (m, 1H), 8.19 (dd, J=5.0, 1.3 Hz, 1H).

Provenance & Evidence