Triethylamine → 1,1-Dimethylethyl 3-[5-(5-{3-chloro-4-[(difluoromethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoate

Participants

Reaction Steps

A solution of 3-chloro-4-[(difluoromethyl)oxy]benzoyl chloride (D18; 69.5 mg, 0.289 mmol) in dry DMF (1 ml) was added to a stirred solution of 1,1-dimethylethyl 3-{5-[(hydroxyamino)(imino)methyl]-1-isoquinolinyl}propanoate (D36; 70 mg, 0.222 mmol) and triethylamine (0.046 ml, 0.333 mmol) in dry DMF (2 ml) at 0° under nitrogen and stirring was continued at room temperature for 50 min, then heated at 100° for 5 h. The cooled mixture was partitioned between saturated aqueous sodium bicarbonate (30 ml) and ethyl acetate (3×20 ml), and the organic layer was washed with 50:50 brine:water and brine, dried (MgSO4) and evaporated in vacuo to give a brown gum. The crude product was purified by flash chromatography on silica gel, eluting with 0-30% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (32 mg).

Provenance & Evidence