Cesium carbonate → HCID 131728809, compound

Participants

Reaction Steps

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (801 mg, 4 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromopyrimidine (636 mg, 4 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1955 mg, 6 mmol), Xantphos™ (174 mg, 0.3 mmol) and tris(dibenzylideneacetone)dipalladium(0) (92 mg, 0.1 mmol) and the mixture was heated under reflux under argon for 1 hour. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with water and brine and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-20% methanol in ethyl acetate to 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (360 mg, 32%). LC/MS [M+H]+=279. (ii) A solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (0.557 g, 2 mmol) in TFA/DCM (1:2, 7.5 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was dried to give crude (4S)-3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylic acid TFA salt (assume ˜2 mmol) which was used in the next step. LC/MS [M+H]+=223.

Provenance & Evidence