Hydrochloric Acid → N-(6-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

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Reaction Steps

The sodium salt of 1,1,1,3,3,3-hexamethyldisilazane (1M solution in THF; 0.592 ml) was added to a solution of 7-amino-6-chlorobenzofuran (0.099 g) in DMF (5 ml) and the reaction mixture was stirred at ambient temperature for 30 minutes. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (0.1 g) was added and the resultant mixture was stirred at ambient temperature for 3 hours. The mixture was partitioned between ethyl acetate and water. The organic phase was washed in turn with water and brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent. The material so obtained was dissolved in methylene chloride and a 5M solution of hydrogen chloride gas in isopropanol (0.088 ml) was added. Diethyl ether was added and the precipitate was isolated and dried under vacuum. There was thus obtained the title compound (0.118 g) as a dihydrochloride salt; NMR Spectrum: (DMSOd6 and CF3CO2D) 2.35 (m, 2H), 3.15 (m, 2H), 3.35 (m, 2H), 3.55 (d, 2H), 3.75 (t, 2H), 4.0 (m, 2H), 4.05 (s, 3H), 4.35 (t, 2H), 7.15 (d, 1H), 7.45 (s, 1H), 7.55 (d, 1H), 7.8 (d, 1H), 8.1 (d, 1H), 8.25 (s, 1H), 8.8 (s, 1H); Mass Spectrum: M+H+ 469.

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