N,N'-Dimethylethylenediamine → (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

Participants

Reaction Conditions

Reaction Steps

Copper (I) iodide (41 mg, 0.22 mmol) was added to a stirred suspension of 4-bromofluorobenzene (0.24 mL, 2.17 mmol), (S)-2-phenoxymethyl-6-trimethylsilanyloxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.37 g, 1.08 mmol), K2CO3 (0.3 g, 2.17 mmol) and N,N′-dimethylethylenediamine (0.070 mL, 0.65 mmol) in toluene (8 mL) in a sealed tube and under nitrogen. The mixture was stirred at 140° C. for 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 residue was dissolved in MeOH (4 mL) and stirred at 100° C. for 10 minutes under microwave irradiation. The solvent was evaporated in vacuo and the residue purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). Desired fractions were collected and the solvents evaporated in vacuo to yield (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (285 mg, 71% yield) as an off-white foam. 1H NMR (400 MHz, CDCl3) δ ppm 2.21 (br. s., 1H), 3.57-3.68 (m, 1H), 3.81 (dt, J=10.9, 4.4 Hz, 1H), 4.13-4.20 (m, 1H), 4.61 (dd, J=13.4, 4.9 Hz, 1H), 4.81 (dd, J=13.4, 2.1 Hz, 1H), 5.10 (s, 2H), 6.95-7.03 (m, 4H), 7.09-7.18 (m, 2H), 7.27-7.35 (m, 4H).

Provenance & Evidence