Diethyl Malonate → HCID 178470166, compound

Participants

Reaction Steps

To a solution of diethyl malonate (4.1 mL, 27 mmol) in 10.0 mL of EtOH at RT was added sodium ethoxide (10 mL of the 21% wt. in denatured ethyl alcohol, 28 mmol) followed by 5 min later, the addition of 1-(2,6-difluorophenyl)-4-nitroso-1H-pyrazol-5-amine (5.13 g, 23 mmol) as a solid. The resulting mixture was refluxed for 4 h. The volatiles were removed under reduced pressure and the remaining residue was partitioned between 50 mL of EtOAc and 30 mL of saturated NH4Cl solution. The precipitated rusty solid was filtered, rinsed with 2×5 mL of water followed by 2×10 mL of EtOAc. The rusty solid was dried in vacuum oven at 45° C. for 4 h to provide 4.3 g of ethyl 1-(2,6-difluorophenyl)-6-hydroxy-1H-pyrazolo[3,4-b]pyrazine-5-carboxylate. The filtrate was transferred to a separatory funnel. The EtOAc layer was separated and washed with brine, dried and concentrated. Purification of the dark brown residue on a silical gel column (25-65% EtOAc in Hexanes) afforded 1.1 g of ethyl 1-(2,6-difluorophenyl)-6-hydroxy-1H-pyrazolo[3,4-b]pyrazine-5-carboxylate as a brown solid. MS (ES+): 321.1 (M+H)+. MS (ES+): 343.0 (M+Na)+.

Provenance & Evidence