Sodium hydride → N-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine

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Under argon, sodium hydride (60%, 372 mg, 9.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (1.67 g, 8.08 mmol) in DMF. After stirring for 30 minutes at ambient temperature, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.3 g, 4.04 mmol) was added and stirring was continued for a further 20 hours. The mixture was poured onto water (130 ml) and extracted with ethyl acetate. The organic layers were washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography on silica, eluting with methylene chloride/methanol (95/5) followed by methylene chloride/methanol containing ammonia (1%) (90/10). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 50° C. to give 4-(4-bromo-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.4 g, 70%).

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