Hydrochloric Acid → 5-fluoro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine

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Reaction Conditions

Reaction Steps

3-Methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (6.42 g, 30 mmol) and 4N hydrogen chloride in dioxane (7.55 ml, 30 mmol) were added to a suspension of 4-chloro-5-fluoroquinazoline (5 g, 27.5 mmol; obtained as described in PCT Int. Appl. WO2001094341, AstraZeneca) in acetonitrile (100 ml). The mixture was stirred at 80° C. for 2 hours. After cooling, the precipitate washed with acetonitrile. This precipitate was partitioned between DCM and 5% aqueous sodium bicarbonate and the pH was adjusted to 8. The organic layer washed with brine and dried over MgSO4. Evaporation of the solvents gave 5-fluoro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (9.3 g, 94%) as a dark gum which crystallised on standing; NMR spectrum (CDCl3); 2.30 (s, 3H), 2.54 (s, 3H), 6.93 (d, 1H), 7.15-7.08 (m, 2H), 7.22 (m, 1H), 7.56 (d, 1H), 7.63 (s, 1H), 7.71 (m, 2H), 8.27 (s, 1H), 8.37 (d, 1H), 8.71 (s, 1H).

Provenance & Evidence