Sodium hydride → 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-1-[3-(N-benzyl-N-methylamino)propyl]-2,4(1H, 3H)-quinazolinedione

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Reaction Conditions

Reaction Steps

A portion (96 mg) of 50% sodium hydride suspension in mineral oil was added to a solution of 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H, 3H)-quinazolinedione (372 mg) in dimethylformamide (20 ml). After stirring the mixture at 100° C. for one hour, 3-(N-benzyl-N-methylamino)propyl chloride hydrochloride (320 mg) was added. The mixture was heated to 140°-145° C. and maintained at this temperature for 6 hours with stirring. The mixture was concentrated under reduced pressure, and the mixture was then partitioned between CHCl3 and 10% aqueous K2CO3 solution. The CHCl3 phase was separated, dried over MgSO4 and concentrated. The residue was chromatographed over a column of silica gel, and the fractions eluted with CHCl3 -methanol (v/v, 9:1) were concentrated and recrystallized from diethyl ether/n-hexane to give 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-1-[3-(N-benzyl-N-methylamino)propyl]-2,4(1H, 3H)-quinazolinedione (355 mg, 66.5%) melting at 145°-146° C. After treating the crystals with ethanol containing hydrogen chloride and recrystallizing from ethanol/diethyl ether, the hydrochloride melting at 207°-209° C. was obtained.

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