Oxalyl chloride → HCID 178447227, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension or solution of carboxylic acid, in this case tiglic acid (0.11 g, 1.1 mmol) in anhydrous acetonitrile (3 mL) is added oxalyl chloride (neat, 100 μL, 1.1 mmol). The mixture is shaken at 65° C. for 30 minutes and then reduced to half volume under reduced pressure. The resulting acetonitrile solution is then added to a solution of (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) and diisopropylethylamine (380 μL, 2.2 mmol) in tetrahydrofuran (3 mL) After stirring overnight at room temperature, the reaction mixture is concentrated to dryness under reduced pressure. Tetrabutylammonium fluoride solution (1.0 M, 2.0 mL, 2.0 mmol) is added and the mixture is shaken at 55° C. for 2 hours and then allowed to cool to room temperature. Following concentration, the residue is triturated with water and the resulting solid collected by filtration, washed with acetonitrile, and dried under house vacuum to give (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide (12 mg, 21%).

Provenance & Evidence