Boron tribromide → 5,7-dihydroxy-3-(4-hydroxyphenyl)-4(3H)-quinazolinethione

Participants

Reaction Conditions

Reaction Steps

5,7-Dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinethione (6.5 g, 19.8 mmol), as prepared in Example 33, was dissolved in 75 ml of CH2Cl2. The solution was cooled to 0° C. and 37 ml of BBr3 (396 mmol) was added dropwise for 1 h 30 min. The reaction mixture was then stirred at room temperature until complete transformation of the starting material as monitored by HPLC. The reaction mixture was evaporated to dryness. A cold saturated solution of NaHCO3 was added and the resulting solid filtered and dried. This solid was mixed with pyridine hydrochloride salt (46 g, 396 mmol). The mixture was heated to 189° C. for 3.5 hours. Subsequently, the reaction was cooled to room temperature. Methanol was added to dissolve the mixture. The obtained dark solution was poured to a saturated NaHCO3 solution and extracted with ethyl acetate. The combined organic phases were washed with brine and dried over MgSO4 to yield a brownish solid that was purified by chromatography on silica gel (loaded with CH2Cl2 and a slight amount of MeOH, eluted with 2%, 2.5%, 3% of MeOH in CH2Cl2) to provide 5,7-dihydroxy-3-(4-hydroxyphenyl)-4(3H)-quinazolinethione (3.4 g, 60%) as a yellow solid.

Provenance & Evidence