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

Participants

Reaction Steps

A solution of 3-cyano-4-[(cyclopropylmethyl)oxy]benzoyl chloride (D25; 54.2 mg, 0.23 mmol) in dry DMF (1.5 ml) was added to a stirred solution of 1,1-dimethylethyl 3-{5-[(hydroxyamino)(imino)methyl]-1-isoquinolinyl}propanoate (D36; 68.9 mg, 0.219 mmol) and triethylamine (0.048 ml, 0.345 mmol) in dry DMF (1.5 ml) at 0° and the mixture was stirred at 0° for 1.5 h. The mixture was then heated at 100° with stirring under nitrogen for 16 h. The cooled mixture was partitioned between saturated aqueous sodium bicarbonate (40 ml) and ethyl acetate (3×25 ml), and the combined organic layers washed with 50:50 brine:water and brine, dried (MgSO4) and evaporated in vacuo to give a brown oil which was purified by flash chromatography on silica gel, eluting with 0-40% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (36 mg)

Provenance & Evidence