2-Bromopyrimidine → Methyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of methyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (316 mg, 2 mmol) (prepared as described in step (ii) of Example 8) in THF (10 ml) was stirred at −40° C. Lithium hexamethyldisilazide (2 ml, 1M solution in THF) was added dropwise and the mixture was stirred at −40° C. for 15 minutes and then at −70° C. for 1 hour. A solution of 2-bromopyrimidine (318 mg, 2 mmol) in THF (1 ml) was added dropwise and the reaction was stirred at −70° C. for 1 hour and then warmed to 0° C. over 1 hour and then stirred at room temperature overnight. The reaction mixture was diluted with citric acid solution and dichloromethane. The organic layer was separated, washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane to give crude methyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (144 mg) which was used in the next step, LC/MS [M+H]+=237. (ii) A stirred solution of methyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (144 mg, 0.6 mmol) in THF (1.5 ml) at 0° C. was treated with lithium hydroxide (72 mg, 3 mmol) in water (1 ml) and the reaction mixture was stirred at 0-5° C. for 1 hours. The reaction was acidified to pH 2 with 2N hydrochloric acid and the solvent was evaporated. The residue dried to give 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylic acid which was used crude in the next step, LC/MS [M+H]+=223.

Provenance & Evidence