Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:13][CH3:14])[C:6]([CH3:12])=[CH:7][CH:8]=2)[N:3]=1.[NH2:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([OH:22])[CH2:18][CH2:17]1.C1CCN2C(=NCCC2)CC1>CC#N>[CH3:14][O:13][C:5]1[C:6]([CH3:12])=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([OH:22])[CH2:18][CH2:17]1)[N:11]=[CH:10]2To a solution of 2-chloro-8-methoxy-7-methylquinazoline (20.4 g, 0.098 mol) in CH3CN (800 mL) were added trans-4-amino-cyclohexanol (22.5 g, 0.195 mol) and DBU (29.7 g, 0.195 mol) in one portion. The reaction mixture was refluxed with stirring overnight. TLC (ethyl acetate/petroleum ether=1:1) indicated the reaction was complete. The solvent was removed in vacuo. The residue was taken up with CHCl3 (550 mL), the solution was washed with water (150 mL×2). The aqueous layer was re-extracted with CHCl3 (150 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give the crude product. The crude product was re-crystallized from EtOH (130 mL)/water (200 mL) to give the title compound (17 g, 60.5%) as an off-white solid.
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