N,N-Dimethylglycine → 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

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Reaction Conditions

Reaction Steps

Copper (I) iodide (7.3 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 (50 mg, 0.19 mmol), 3-bromopyridine (0.073 mL, 0.76 mmol), cesium carbonate (0.25 g, 0.77 mmol) and N,N-dimethylglycine (7.89 mg, 0.077 mmol) in 1,4-dioxane (1 mL) in a sealed tube and under nitrogen. The mixture was stirred at 100° C. for 16 hours. More copper (I) iodide (7.3 mg, 0.038 mmol) was added, N,N-dimethylglycine (7.89 mg, 0.077 mmol), cesium carbonate (0.25 g, 0.77 mmol) 3-bromopyridine (0.073 mL, 0.76 mmol) were added and the mixture was stirred at 130° C. for another 24 hours. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (7 mg, 11% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 4.13-4.22 (m, 2H), 4.55 (dd, J=6.8, 5.3 Hz, 2H), 5.17 (s, 2H), 7.03 (s, 1H), 7.10-7.18 (m, 2H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.28-7.36 (m, 3H), 8.25 (dd, J=4.6, 1.2 Hz, 1H), 8.41 (d, J=2.9 Hz, 1H).

Provenance & Evidence