Isobutyl chloroformate (0.845 g, 6.2 mmol) and N-methylmorpholine (0.963 g, 9.52 mmol) were added to an ice cold solution of 2.100 g (9.52 mmol) of 4-[bis-(2-methoxy-ethyl)-amino]-but-2-ynoic acid in 50 mL of tetrahydrofuran under nitrogen. After stirring for 30 min, a solution of 1.500 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 10 mL of pyridine was added and the mixture was stirred for 2 hr at 0° C. The reaction was then quenched with ice water, poured into saturated sodium bicarbonate, and the product was extracted with ethyl acetate. Chromatography of the extract on silica gel, eluting with methanol/ethyl acetate (15:85), gave 0.660 g of 4-[Bis-(2-methoxy-ethyl)-amino]-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide: mass spectrum (m/e): M+H 512.
