To a solution of 1.44 g (17.14 mmol) of 2-butynoic acid and 2.26 g (16.5 mmol) of isobutyl chloroformate in 30 ml of tetrahydrofuran at 0° C., with stirring, was added 3.1 g (3.4 mmol) of N-methyl morpholine. This solution of the mixed anhydride was added to a stirred solution of 1.13 g (3.06 mmol) of 6-amino-4-[(3-bromophenyl)amino]-7-methoxy-3-quinolinecarbonitrile in 30 ml tetrahydrofuran in three portions over a 24 hour period. The solvent was removed. The residue was stirred with dilute sodium bicarbonate solution. Solid was collected and washed with water and ether. This was recrystallized from 1-butanol. The resulting solid was taken up in hot tetrahydrofuran and filtered through silica gel. The filtrate was concentrated and diluted with hexanes to give 0.71 g of N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl]-2-butynamide as a yellow powder: mass spectrum (electrospray, m/e): M+H 437.1,438.1.
