Potassium ethyl malonate → ethyl [6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazin-3-ylcarbonyl]acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazine-3-carboxylic acid (12.5 g) and carbonyl di-imidazole (6.0 g) was heated at 5° C. for 1 hour. Separately, a mixture of potassium ethyl malonate (7.0 g), triethylamine (8.0 ml) and anhydrous magnesium chloride (5.0 g) in acetonitrile (200 ml) was stirred at ambient temperature for 2 hours. The two mixtures were combined and stirred for 18 hours at ambient temperature, then at reflux for 1 hour. The solvents were evaporated, and the residue partitioned between dichloromethane and 2N HCl. The organic solution was dried (MgSO4) and evaporated. The resulting residue was purified by flash chromatography, eluting with diethyl ether, to give ethyl [6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazin-3-ylcarbonyl]acetate (12.5 g) as a yellow gum.

Provenance & Evidence