Hydrochloric Acid → [4-(3-Pyrimidylcarboxyamino)-2-phenylbenzoyl]methionine methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of the 5-pyrimidinecarboxylic acid methyl ester prepared in Example 219A (682 mg, 4.94 mmol) and aqueous sodium hydroxide solution (4.0 M, 2.5 mL) in THF was heated at 60° C. for 1.5 hours. Hydrochloric acid (6.0 N, 2 mL) was added to the reaction mixture, and the solvent was evaporated in vacuo. The residue was dried under high vacuum at 50° C. for 1 hour, and the redesolved in to THF. To the acid solution was added (4-amino-2-phenylbenzoyl)methionine methyl ester (compound 8, 1.97 g, 5.0 mmol), 3-hydroxy 1,2,3-benzotriazin-4(3H)-one (0.978 g, 6.0 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.15 g, 6.0 mmol) and triethylamine (2.8 mL, 20 mmol). After 14 hours, the reaction mixture was diluted with ethyl acetate (100 mL), washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was then purified by column chromatography (50% ethyl acetate-hexane, then ethyl acetate) to give [4-(3-pyrimidylcarboxyamino)-2-phenylbenzoyl]methionine methyl ester (0.937 g, 41%).

Provenance & Evidence