Oxalyl chloride → (E)-N-{4-[4-(benzyloxy)-3-chloroanilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide

Participants

Reaction Steps

A 1.74 ml (2.54 g, 0.02 moles) portion of oxalyl chloride was added to 3.31 grams (0.02 moles) of (E)-4-(dimethylamino)-2-butenoic acid hydrochloride in 75 ml of acetonitrile. To this was added a small drop of dimethylformamide. The reaction was heated and stirred in an oil bath at 63° for 20 minutes, giving an orange solution. This solution as concentrated in vacuo without the application of heat to about half its original volume. This solution was cooled in an ice bath and a solution of 4.45 g (0.01 moles) of the 6-amino-4-[4-(benzyloxy)-3-chloroanilino]-7-ethoxy-3-quinolinecarbonitrile in 50 ml of N-methylpyrrolidone was added in a stream. The reaction was cooled and stirred for 2 hours. The reaction was poured onto 100 ml of saturated aqueous sodium bicarbonate in ice. On standing the resulting gum solidified and the solid was filtered. This solid was chromatographed on silica gel. The column was washed with 3 liters of 1:19 methanol-ethyl acetate, then the product was eluted with 3 liters of 1:5:94 triethylamine-methanol-ethyl acetate. Concentration of the eluate gave a solid, which was filtered to give 2.96 grams of the title compound. From the filtrate was obtained an additional 1.0 grams of product. Total: 3.96 g.

Provenance & Evidence