4-Methylmorpholine → HCID 178454204, compound

Participants

Reaction Steps

A suspension of 5.78 g (25 mmol) of 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid and 100 ml of acetonitrile is stirred at room temperature and 5.25 g (52 mmol) of triethylamine is added. The mixture is stirred for 1 hr and the resulting solution is added to a solution of mixed anhydride prepared as follows. A suspension of 9.24 g (37.5 mmol) of N-t-butoxycarbonyl-L-glutamine and 200 ml of acetonitrile is stirred at 0° C. and 7.58 g (75 mmol) of N-methylmorpholine is added. The resulting solution is cooled to -30° C. and 4.52 g (37.5 mmol) of pivaloyl chloride is added and stirring is continued at -10°±5° C. for 1 hr. The pyrimidine acid solution is added, keeping the temperature below -10° C., and stirring is continued for 2 hrs and the reaction is placed in an ice bath and allowed to warm to room temperature overnight. The solvent is evaporated and the residue dissolved in ice water. The pH is adjusted to 3.2 with solid citric acid and the resulting precipitate is filtered, washed with water, and redissolved in ethanol. The solution is clarified by filtration and the filtrate evaporated. The residue is triturated with ether, filtered, and the precipitate washed with ether, and dried to give 7.5 g of 2-[4-(N-t-butoxycarbonyl-L-glutaminylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid; [α]D23 -16° (cl, pH 7).

Provenance & Evidence