Cesium carbonate → HCID 67103419, compound

Participants

Reaction Steps

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (300 mg, 1.5 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromo-6-methylpyridine (258 mg, 1.5 mmol) in 1,4-dioxane (10 ml) was treated with cesium carbonate (733 mg, 2.25 mmol), Xantphos™ (65.1 mg, 0.113 mmol) and tris(dibenzylideneacetone)dipalladium(0) (34.3 mg, 0.038 mmol) and the mixture was heated under reflux under argon for 18 hours. 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 0-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (246 mg, 56%). LC/MS [M+H]+=292. (ii) A solution of 1,1-dimethylethyl 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (246 mg, 0.84 mmol) in TFA/DCM (1:2, 6 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was dried to give 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜0.84 mmol) which was used in the next step. LC/MS [M+H]+=236.

Provenance & Evidence