Triethylamine → 1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Participants

Reaction Steps

Oxalyl chloride (571 mg, 4.5 mmol) was added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (available from AK Scientific Product Catalog; 800 mg, 3.90 mmol) in dichloromethane (15 ml) followed by DMF (catalytic amount). The reaction mixture was stirred for 45 minutes, further oxalyl chloride (0.1 ml) and DMF (1 drop) were added and stirring continued for 20 minutes. The solvent was evaporated, the residue was co-evaporated with toluene then dried under high vacuum for 30 minutes. The crude acid chloride was dissolved in acetonitrile (10 ml) and added to a suspension of 1,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 17; 916 mg, 3.00 mmol) and triethylamine (607 mg, 6.00 mmol) in acetonitrile (15 ml). The reaction mixture was stirred at room temperature for 40 minutes then heated under reflux for 24 hours. The reaction mixture was cooled and the solvent evaporated. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase was separated, washed with brine, dried (MgSO4) and evaporated to give the crude product (1.3 g). The residue was purified by chromatography, eluting with 8-38% ethyl acetate in cyclohexane, to give the title compound (486 mg).

Provenance & Evidence