Phosgene → 4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid (3-methyl-pyridin-2-yl)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-amino-3-picoline (26 μL, 0.204 mmol) and triethylamine (63 μL, 0.448 mmol) in 5 mL methylene chloride at −40° C. was slowly added a 20% solution of phosgene in THF (118 μL, 0.224 mmol). The reaction mixture was stirred at −40° C. for 1 hr and then a solution of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride (100 mg, 0.204 mmol) and triethylamine (57 μl, 0.408 mmol) in 8 ml of 1-methyl-2-pyrrolidinone was slowly added and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic layer was dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography (eluting with ethyl acetate/hexane) to yield 4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid (3-methyl-pyridin-2-yl)-amide (18 mg, 16%). ES-MS calcd for C28H25F3N6O3 (m/e) 550.6, obsd 551.1 (M+H).

Provenance & Evidence