Example 2 Steps for the synthesis of 2,4-diaminoquinazolin-6-yl-2,5-dimethoxybenzoate (Compound 32):
Step I: 2-fluoro-5-methoxybenzonitrile (10 g, 0.066 mol) was dissolved in dry dichloromethane (DCM, 200 ml) and cooled to 0 °C. Boron tribromide (BBr3, 16 ml, 0.0092 mol) was slowly added under stirring, followed by warming the reaction mixture to room temperature and continuous stirring for 2 days. After completion of the reaction, the reaction was quenched with 10% sodium bicarbonate solution (50 ml). The aqueous layer was separated and extracted with dichloromethane (2 x 200 ml). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the Step I product 2-fluoro-5-hydroxybenzonitrile (5.5 g, 61% yield). Thin layer chromatography (TLC) showed Rf = 0.4 (Expander: chloroform:methanol = 9:1).
