HCID 86670204, compound → HCID 57410026, compound

Participants

Reaction Steps

2-(6-Chloro-pyridazin-3-yloxymethyl)-5-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (74 mg, 0.2 mmol) was dissolved in a mixture of TEA (0.2 mL), MeOH (1.6 mL) and THF (2.4 mL). The solution was hydrogenated in a H-Cube reactor (1 ml/min, 30 mm 10% Pd/C cartridge, full H2 mode, 40° C., 1 cycle). The solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 N solution of ammonia in MeOH in DCM 0/100 to 10/90). The desired fractions were collected and the 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% MeOH to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 100% MeOH) to yield 5-(4-fluoro-phenyl)-2-(pyridazin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (17 mg, 24% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.18 (dd, J=6.8, 5.2 Hz, 2H), 4.56 (dd, J=6.8, 5.2 Hz, 2H), 5.64 (s, 2H), 7.05 (dd, J=9.0, 1.4 Hz, 1H), 7.08 (s, 1H), 7.09-7.17 (m, 2H), 7.29-7.35 (m, 2H), 7.40 (dd, J=8.9, 4.5 Hz, 1H), 8.88 (dd, J=4.4, 1.4 Hz, 1H).

Provenance & Evidence