1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

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Reaction Steps

Methyl {2-chloro-8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate (52.5 g) is dissolved in 1,4-dioxane (100 ml), 3-methoxyphenylpiperazine (25.8 g) and DBU (20.4 g) are added at room temperature, the temperature increasing. The mixture is stirred under reflux for 22 h, then cooled to room temperature, diluted with ethyl acetate (500 ml) and water (200 ml) and the phases are separated. The organic phase is washed with 0.2N hydrochloric acid (three times 100 ml) and water (200 ml), dried over sodium sulphate and concentrated in a rotary evaporator. A total of 62.5 g of methyl {8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate is obtained as a solidified foam, which is reacted as the crude product without further purification.

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