Under N2 atmosphere Sodium hydride (23.0 mg, 0.910 mmol) was suspended in anhydrous N,N-Dimethylformamide (3.0 mL, 39 mmol), cooled with ice bath and stirred for 10 min. 4-hydroxyquinazoline (0.120 g, 0.821 mmol) was added and the clear solution was stirred at r.t. for 10 min, cooled with ice bath. Methyl 3-(bromomethyl)-4-cyano-5-(morpholin-4-yl)thiophene-2-carboxylate (0.203 g, 0.588 mmol) was added and the reddish-brown solution was stirred with cooling for 40 min. The mixture was quenched with saturated NH4Cl aqueous solution, extracted with EtOAc. The EtOAc solution was washed with water (3×) then brine, dried over Na2SO4, filtered, rotavaped to give a crude solid. Chromatograph in a silica gel column using MeOH/DCM (0/100 to 5/95) afforded a solid product (0.211 g, yield 87.4%). LC/MS: (FA) ES+ 411. 1H NMR (400 MHz, d-chloroform) δ 8.30 (m, 1H), 8.26 (s, 1H), 7.68-7.76 (m, 2H), 7.45-7.49 (m, 1H), 5.43 (s, 2H), 3.83-3.85 (m, 4H), 3.82 (s, 3H), 3.59-3.62 (m, 4H).
