Dimethylformamide → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

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Reaction Steps

6-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (1.22 g) was stirred in thionyl chloride (10 ml) with dimethylformamide (0.1 ml) at 85° C. for 1 hour. The reaction was evaporated to dryness, and then azeotroped with toluene. The residue was partitioned between methylene chloride and saturated sodium bicarbonate. The organic phase was separated and evaporated to dryness. The saturated sodium bicarbonate phase was basified with 2M sodium hydroxide and was extracted with methylene chloride. The two organic phases were combined and dried over sodium sulphate, filtered and the filtrate evaporated to dryness. This residue was purified by eluting through a silica column with 5% methanol in methylene chloride to yield 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline as a solid, (0.5 g, 39%); NMR: 1.95 (m, 2H), 2.4 (broad m, 6H), 3.55 (m, 4H), 3.98 (s, 3H), 4.26 (t, 2H), 7.36 (s, 1H), 7.41 (s, 1H), 8.83 (s, 1H); m/s: M+H+ 338, 340.

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