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

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To a solution of 1,1-dimethylethyl 1-[4-(ethyloxy)-4-oxobutyl]-6-[(hydroxyamino)(imino)methyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 27; 240 mg, 0.572 mmol) in N,N-dimethylformamide (DMF) (4 ml) was added triethylamine (0.119 ml, 0.858 mmol) followed by 3-cyano-4-[(1-methylethyl)oxy]benzoyl chloride (WO 2008128951; 141 mg, 0.629 mmol) in DMF (2 ml) dropwise over one minute at room temperature under nitrogen. The resulting mixture was stirred for 1 h at room temperature, then warmed up to 120° C. After 2 h at 120° C., most of the solvent was removed, and the residue diluted with ethyl acetate. The solution was washed with sodium bicarbonate then brine, dried over MgSO4 and concentrated in vacuo to give the crude product (ca. 300 mg). Purification by flash chromatography on silica gel, eluting with 8-38% ethyl acetate in cyclohexane, gave the title compound (120 mg) as a white foam.

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